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Adrenocorticoids & Adrenocorticoids & adrenocortical adrenocortical antagonists antagonists Huifang Tang Email: [email protected]
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Adrenocorticoids & adrenocortical antagonists

Jan 15, 2016

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Page 1: Adrenocorticoids & adrenocortical antagonists

Adrenocorticoids amp Adrenocorticoids amp adrenocortical adrenocortical

antagonists antagonists

Huifang TangEmail tanghuifangzjueducn

History(1)bull In 1849 In 1849 AddisonAddison first appreciated the importance of the adrenal first appreciated the importance of the adrenal

glandsglands

bull Addison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules LoAddison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules London UK Samuel Highley 1855 ndon UK Samuel Highley 1855

Structure and function of adrenal Structure and function of adrenal cortexcortex

ZonaZonaReticularisReticularis

AdrenalineAdrenaline

ZonaZonaFaseciculataFaseciculata

AndrogensAndrogens

bull Adrenocortical Adrenocortical hormoneshormones

bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee

bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol

bull Sex hormonesSex hormones androgens androgens

History(2)bull As early as 1912 Cushing described

patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity

History(3)

bull In 1948 the role of hypothalamus in pituitary control was established by Harris

bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 2: Adrenocorticoids & adrenocortical antagonists

History(1)bull In 1849 In 1849 AddisonAddison first appreciated the importance of the adrenal first appreciated the importance of the adrenal

glandsglands

bull Addison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules LoAddison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules London UK Samuel Highley 1855 ndon UK Samuel Highley 1855

Structure and function of adrenal Structure and function of adrenal cortexcortex

ZonaZonaReticularisReticularis

AdrenalineAdrenaline

ZonaZonaFaseciculataFaseciculata

AndrogensAndrogens

bull Adrenocortical Adrenocortical hormoneshormones

bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee

bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol

bull Sex hormonesSex hormones androgens androgens

History(2)bull As early as 1912 Cushing described

patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity

History(3)

bull In 1948 the role of hypothalamus in pituitary control was established by Harris

bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 3: Adrenocorticoids & adrenocortical antagonists

Structure and function of adrenal Structure and function of adrenal cortexcortex

ZonaZonaReticularisReticularis

AdrenalineAdrenaline

ZonaZonaFaseciculataFaseciculata

AndrogensAndrogens

bull Adrenocortical Adrenocortical hormoneshormones

bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee

bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol

bull Sex hormonesSex hormones androgens androgens

History(2)bull As early as 1912 Cushing described

patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity

History(3)

bull In 1948 the role of hypothalamus in pituitary control was established by Harris

bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 4: Adrenocorticoids & adrenocortical antagonists

bull Adrenocortical Adrenocortical hormoneshormones

bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee

bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol

bull Sex hormonesSex hormones androgens androgens

History(2)bull As early as 1912 Cushing described

patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity

History(3)

bull In 1948 the role of hypothalamus in pituitary control was established by Harris

bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 5: Adrenocorticoids & adrenocortical antagonists

History(2)bull As early as 1912 Cushing described

patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity

History(3)

bull In 1948 the role of hypothalamus in pituitary control was established by Harris

bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 6: Adrenocorticoids & adrenocortical antagonists

History(3)

bull In 1948 the role of hypothalamus in pituitary control was established by Harris

bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 7: Adrenocorticoids & adrenocortical antagonists

ContentsContents

bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid

synthetase inhibitorssynthetase inhibitors

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 8: Adrenocorticoids & adrenocortical antagonists

Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs

AA BB

CC DD

甾甾

甾体结构甾体结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 9: Adrenocorticoids & adrenocortical antagonists

Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))

11 22

33 44

5566 77

881010 99

121213131414 1515

1616 1818

1919

AA BB

CC DD

基本结构基本结构

HH

AA Glucocorticoid drugs Glucocorticoid drugs

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 10: Adrenocorticoids & adrenocortical antagonists

HH

Cortisone( 可的松 )

Prednisone( 泼尼松 )

(( 地塞米地塞米松松 ))

Hydrocortisone( 氢化可的松

Cortisol)

Prednisolone( 泼尼松龙 )

Fluocinolone( 氟轻松 )

HH

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 11: Adrenocorticoids & adrenocortical antagonists

Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions

binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)

nuclear translocationnuclear translocation

binding to GRE or nGREbinding to GRE or nGRE

regulating related gene regulating related gene transcriptiontranscription

biological effects (usually slow) biological effects (usually slow)

AA Glucocorticoid drugs

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
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  • Slide 49
  • Slide 50
  • Slide 51
Page 12: Adrenocorticoids & adrenocortical antagonists

Action mode of glucocorticoid drugs

CBG corticosteroid binding globulin

S glucocorticoid steroids

GR glucocorticoid receptor

HSP heat shock protein

IP immunophilin

GRE glucocorticoid-response element

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 13: Adrenocorticoids & adrenocortical antagonists

Nuclear translocation of glucocorticoid receptors (GR)

Dexamethasone was used

GR was labeled with green fluorescent protein

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
  • Slide 3
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Page 14: Adrenocorticoids & adrenocortical antagonists

1 Pharmacological effects

Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects

AA Glucocorticoid drugs Glucocorticoid drugs

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 15: Adrenocorticoids & adrenocortical antagonists

(1) Effects on metabolisms

①Glucose metabolism gluconeogenesis glucose

utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat

redistribution (central obesity moon face buffalo hump etc)

④Water and electrolytic metabolism

water excretion Na+ excretion

K+ excretion Ca2+ excretion and absorption

AA Glucocorticoid drugs Glucocorticoid drugs

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 16: Adrenocorticoids & adrenocortical antagonists

Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
  • Slide 3
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Page 17: Adrenocorticoids & adrenocortical antagonists

(2) Permissive actionPotentiating the effects of catecholamines and

glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )

AA Glucocorticoid drugs Glucocorticoid drugs

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 18: Adrenocorticoids & adrenocortical antagonists

One of glucocorticoidrsquos anti-inflammatory actions

Inhibition of proinflammatory gene transcription (AP-1 and NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 19: Adrenocorticoids & adrenocortical antagonists

a) Increasing inflammation related proteins or enzymes

inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF

inducing vasocortin decreasing microvascular permeability

inhibiting the expression of PLA2 COX-2 inducible NOS etc

b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc

c) Inhibiting adhesion molecules

d) Inducing the apoptosis of inflammatory cells

AA Glucocorticoid drugs Glucocorticoid drugs

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 20: Adrenocorticoids & adrenocortical antagonists

(4) Effects on immune and allergy

Suppressing immunological functions and allergy

a) inducing apoptosis of T and B lymphocytes

b) inhibiting transcription factor activity(eg AP-1 NFB)

AA Glucocorticoid drugs Glucocorticoid drugs

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 21: Adrenocorticoids & adrenocortical antagonists

(5) Anti-shock Septic shock

a) improving cardiovascular functions

b) inhibiting the production of inflammatory factors

c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)

d) increasing the tolerance to endotoxin from bacteria

AA Glucocorticoid drugs Glucocorticoid drugs

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 22: Adrenocorticoids & adrenocortical antagonists

(6) Other effects

a) antipyretic effects

b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )

eosinophils platelets

c) skeletal system osteoporosis

d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)

AA Glucocorticoid drugs Glucocorticoid drugs

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 23: Adrenocorticoids & adrenocortical antagonists

2 ADME and properties of commonly used drugs

Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver

Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)

AA Glucocorticoid drugs Glucocorticoid drugs

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 24: Adrenocorticoids & adrenocortical antagonists

Commonly used drugs

Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松

Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙

Long-acting dexamethasone 地塞米松

Topical fluocinolone 氟轻松

AA Glucocorticoid drugs Glucocorticoid drugs

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 25: Adrenocorticoids & adrenocortical antagonists

CortisonCortisonee

可的松可的松

HydrocortisoHydrocortisonene

氢化可的松氢化可的松

CortisolCortisol

PrednisoPrednisonene

泼尼松泼尼松

PrednisolPrednisoloneone

泼尼松龙泼尼松龙

FluocinoloFluocinolonene

氟轻松氟轻松地塞米松地塞米松

HH

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 26: Adrenocorticoids & adrenocortical antagonists

3 Clinical uses

(1) Immune diseases

a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc

b) rejection of organ transplantation

c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc

AA Glucocorticoid drugs Glucocorticoid drugs

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 27: Adrenocorticoids & adrenocortical antagonists

(2) Severe infection and inflammation

a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving

Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration

Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms

b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc

AA Glucocorticoid drugsGlucocorticoid drugs

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
  • Slide 3
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Page 28: Adrenocorticoids & adrenocortical antagonists

(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined

with antimicrobial drugswith antimicrobial drugs

(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc

(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)

(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc

AA Glucocorticoid drugs

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 29: Adrenocorticoids & adrenocortical antagonists

4 Adverse effects of glucocorticoid

drugs

Effects resulting from continued used of large doses

AA Glucocorticoid drugs

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 30: Adrenocorticoids & adrenocortical antagonists

4 Adverse effects

(1) Effects resulting from continued used of large doses

a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc

b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be

administered with GCs

c) Ingestive system peptic ulcers etc

AA Glucocorticoid drugsGlucocorticoid drugs

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 31: Adrenocorticoids & adrenocortical antagonists

d) Cardiovascular system hypertension arteriosclerosis

e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women

f) CNS behavioral disturbances induction of epileptic seizures

g) Inhibition or arrest of growth in children

AA Glucocorticoid drugsGlucocorticoid drugs

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 32: Adrenocorticoids & adrenocortical antagonists

Suppression of hypothalamic-pituitary-adrenal axis

and glucocorticoid drugs

‒‒

ACTH

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 33: Adrenocorticoids & adrenocortical antagonists

(2) Withdrawal syndrome

a) Suppression of hypothalamic-pituitary-adrenal axis

b) Exacerbation of the underlying diseases (rebound)

(3) Contraindications

psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc

AA Glucocorticoid drugs Glucocorticoid drugs

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
  • Slide 2
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Page 34: Adrenocorticoids & adrenocortical antagonists

Balance the ratio of benefit risk before the use of GCs

AA Glucocorticoid drugsGlucocorticoid drugs

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 35: Adrenocorticoids & adrenocortical antagonists

5 Applications

(1) Replacement therapy usually using hydrocortisone

(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone

(3) Long-term therapy oral prednisone or prednisolone

morning single dose

alternate-day therapy

Notes for less severe and less sustained patients

less suppression on hypothalamic-pituitary-adrenal (HPA) axis

(4) Tipical applications skin eye respiratory tract

AA Glucocorticoid drugsGlucocorticoid drugs

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

  • Slide 1
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Page 36: Adrenocorticoids & adrenocortical antagonists

bull Aldosterone 醛固酮

bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of

water and electrolytes

BB Mineralocorticoid drugsMineralocorticoid drugs

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 37: Adrenocorticoids & adrenocortical antagonists

Action of aldosterone on mineralocorticoid receptor

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 38: Adrenocorticoids & adrenocortical antagonists

Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein

AIP

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 39: Adrenocorticoids & adrenocortical antagonists

bull 1 Adrenocorticotropic hormone (ACTH)

bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of

adrenocortical hoemones after long-term glucocorticoid drug use

bull Easily inducing allergy to ACTH

CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase

inhibitorsinhibitors

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 40: Adrenocorticoids & adrenocortical antagonists

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response

ndash plasma cortisol levels are elevated

bull Abnormal responsendash plasma cortisol level are unchanged

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 41: Adrenocorticoids & adrenocortical antagonists

bull 2 Corticosteroid synthetase inhibitors

bull Mitotane 米托坦

bull Metyrapone 美替拉酮

bull Aminoglutethimide 氨鲁米特

bull Used for adrenocortical tumors or hypercorticism

C Adrenocorticotropic hormone and corticosteroid synthetase

inhibitors

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 42: Adrenocorticoids & adrenocortical antagonists

Cortisol Suppression Tests

bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 43: Adrenocorticoids & adrenocortical antagonists

Diagnosis of H-P-A Axis statusH-P suppression test

bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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Page 44: Adrenocorticoids & adrenocortical antagonists

Diagnosis of H-P-A Axis statusAdrenocortical function test

bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged

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