HORMONAL DRUGS Lector prof. Posokhova K.A.. Hormones I Protein-peptide: I Protein-peptide: 1. Hypothalamus 2. Pituitary gland 2. Pituitary gland 3. Parathyroid.

HORMONAL DRUGSHORMONAL DRUGS

Lector prof. Posokhova K.A.Lector prof. Posokhova K.A.

HormonesHormones

I I Protein-peptideProtein-peptide:: 1. 1. Hypothalamus Hypothalamus 2. 2. Pituitary glandPituitary gland 3. 3. Parathyroid glandsParathyroid glands 4. 4. Pancreas Pancreas 5. 5. IntestinalIntestinal II II Derivatives of amine acidsDerivatives of amine acids:: 1. 1. Thyroid glandThyroid gland – – derivatives of thyroninderivatives of thyronin 2. 2. Medulla of adrenal glandsMedulla of adrenal glands – – catecholaminescatecholamines

IIIIII SteroidSteroid::

1. 1. Adrenal cortexAdrenal cortex 2. 2. Sex glandsSex glands

Hormones and hormonal drugs of Hormones and hormonal drugs of protein and polypeptide structureprotein and polypeptide structure

Influence of insulin on Influence of insulin on metabolismmetabolism

Type of metabolism

Stimulation Depression

Carbohydrate Synthesis of glycogen (in liver and muscles)

Transport of glucose into a cell GlycolysisPhosphorilation of glucose

Glycogenolysis Gluconeogenesis Glycosylying of proteins

Fat Synthesis of triglyceridesSynthesis of fatty acids Income of glucose in adipocytesActivity of lipoprotein lipase

Lipolysis Production of keton bodies

Protein Synthesis of proteinsAbsorption of amine acids

Disintegration of protein

Nucleonic acids

Synthesis of cyclic nucleotides (c-AMP and c-GMP)

Absorption of nucleonic acidsSynthesis of RNA and DNABiosynthesis of ribonucleotides

Metabolic Changes Occurring When Metabolic Changes Occurring When Insufficient Insulin is ReleasedInsufficient Insulin is Released

• HyperglycemiaHyperglycemia: Increased blood sugar

• GlycosuriaGlycosuria: Sugar is spilled into the urine

• PolyphagiaPolyphagia: Increased hunger

• PolydipsiaPolydipsia: Increased thirst

• LipolysisLipolysis: Fat breakdown

• KetosisKetosis: Ketones cannot be removed effectively

• AcidosisAcidosis: Liver cannot remove all of the waste products

Disorders Associated With DiabetesDisorders Associated With Diabetes

• Atherosclerosis:Atherosclerosis: Heart attacks and strokes related to the development of atherosclerotic plaques in the vessel lining

• Retinopathy:Retinopathy: With resultant loss of vision as tiny vessels in the eye are narrowed and closed

• Neuropathies:Neuropathies: With motor and sensory changes in the feet and legs and progressive changes in other nerves as the oxygen is cut off

• Nephropathy:Nephropathy: With renal dysfunction related to changes in the basement membrane of the glomerulus

Classifications of Diabetes MellitusClassifications of Diabetes Mellitus

• Type 1, insulin-dependent diabetes Type 1, insulin-dependent diabetes mellitus (IDDM) mellitus (IDDM) – Usually a rapid onset; seen in younger people– Connected in many cases to viral destruction

of the beta cells of the pancreas

• Type 2, nonType 2, non––insulin-dependent diabetes insulin-dependent diabetes mellitus (NIDDM)mellitus (NIDDM)– Usually occurs in mature adults – Has a slow and progressive onset

Insulin drugsInsulin drugs Group Onset Duration of

actionTrade names Routs of

introduction

1. Simple (short duration of action)

20-40 min 4-6-8 hours Iletin, Insul-rapid, Humalog, Humalin R, Actrapid

S.c., i.m.,

i.v.

2. Medium (moderate) acting (on neutral protamine of Hagedorne - NPH

1-1,5 hour 12-14 hours Insuman, Humulin N

S.c., i.m.

3. Long acting (contain Zinc)

6-8 hours 24 hours (till 36 hours)

Insulin-Zn-suspension, Ultratard n-m

S.c., i.m.

4. Standard mixtures of drugs of 1st group with NPH-insulins

20-60 min Till 18 hours Insuman Comb: 30% / 70%, 25% / 75%, 20% / 80%, 10% / 90%

S.c., i.m.

Types of Insulin DeliveryTypes of Insulin Delivery

• Past– Subcutaneous injectionSubcutaneous injection

• Present– Subcutaneous injection, insulin jet Subcutaneous injection, insulin jet

injector, insulin pen, extended insulin injector, insulin pen, extended insulin pump, long-acting insulinpump, long-acting insulin

• Future– Implantable insulin pump, insulin patch, Implantable insulin pump, insulin patch,

inhaled insulininhaled insulin

Rules of mixing drugs of insulinRules of mixing drugs of insulin

1. Never mix crystal zinc-insulins of the 3d group (ultralente) with simple insulin because the Zn2+ partially transforms simple insulin to prolonged form. Therefore its absorption decreases and onset becomes longer. Insulins of these groups should be introduced separately, using different places for injection.

2. Insulin-zinc-suspensions should no be mixed with drugs that contain phosphates because due to this zinc phosphate is produced that leads to decreasing of duration action of zinc-insulins.

3. Never mix insulins with different pH level in one syringe. For example, acid insulins of short action aren’t combinable with NPH-insulins, and surphen –insulins should not be combined with neutral drugs with short action.

Indication for usage of insulin drugsIndication for usage of insulin drugs::

Patients with diabetes mellitusPatients with diabetes mellitus::

1. Absolutely indicated in case of diabetic coma and precoma.

2. Diabetes mellitus of I type if diet therapy and other sugar decreasing means aren’t enough effective.

3. Diabetes of any type if it is accompanied by complications (ketoacidosis, infection, gangrene etc.)

4. Surgeries, pregnancy.

Other casesOther cases::

5. In case of long-lasting exhausting illnesses.6. In case of heart, liver, kidney diseases the drugs are

administered with glucose or as a component of polarizing mixture.

7. Shock therapy of schizophrenia.

Variants of insulin therapyVariants of insulin therapy

1. 1. traditional traditional 2.2. intensive intensive

Traditional insulin therapyTraditional insulin therapy

• adjusting of lifestyle and nutrition of patient at adjusting of lifestyle and nutrition of patient at strictly established dose of insulinstrictly established dose of insulin. .

The simplest variantThe simplest variant – – is administration of is administration of standard mixtures of short and NPH-insulin in standard mixtures of short and NPH-insulin in two injectionstwo injections: 2/3 : 2/3 of dose before breakfast, of dose before breakfast, 1/3 – 1/3 – before dinnerbefore dinner..

• AdvantagesAdvantages:: simplicity of simplicity of performing performing, , glycemia glycemia needs not to be controlled often, control is needs not to be controlled often, control is possible according to level of glucosuriapossible according to level of glucosuria

• DisadvantagesDisadvantages:: hyperinsulinemiahyperinsulinemia, , which which demands additional mealsdemands additional meals, , larger risk of larger risk of hypoglycemiahypoglycemia, , increased frequency of increased frequency of late late complicationscomplications of diabetes mellitusof diabetes mellitus, , bad bad compensation compensation of sugar levelof sugar level

Intensive Intensive ((basis-bolusbasis-bolus) ) insulin therapyinsulin therapy• the patient himself makes daily a selection of insulin the patient himself makes daily a selection of insulin

dose based on measuring of glycemia level with dose based on measuring of glycemia level with glucometrglucometr. . Insulin of medium durability is used twice Insulin of medium durability is used twice a day (to create a basal level of hormone) and before a day (to create a basal level of hormone) and before the breakfast, lunch and dinner additionally insulin the breakfast, lunch and dinner additionally insulin of short action duration is introducedof short action duration is introduced ( (imitation of imitation of bolus physiological secretion of insulin as a respond bolus physiological secretion of insulin as a respond to food consumption)to food consumption)..

• AdvantagesAdvantages:: effective compensation of glycemiaeffective compensation of glycemia, , more liberal diet more liberal diet ((only easy assimilable only easy assimilable carbohydrates and alcohol are prohibited)carbohydrates and alcohol are prohibited), , flexible flexible day scheduleday schedule, , decreasing risk decreasing risk of development of late of development of late complicationscomplications

• DisadvantagesDisadvantages:: it is necessary to constantly it is necessary to constantly control glycemiacontrol glycemia, , teaching the patientteaching the patient ( (additional additional expensesexpenses), ), often lightoften light hypoglycemiahypoglycemia

TREATMENT OF HYPERGLYCEMIC TREATMENT OF HYPERGLYCEMIC KETOACIDIC COMAKETOACIDIC COMA

1.1. Introduction of insulinIntroduction of insulin ((only insulin of short action is usedonly insulin of short action is used) )

• intravenously dropplyintravenously dropply counting 0,1 О0,1 ОDD//kgkg of body weight per hourof body weight per hour. First two hours – with the speed of 8 ОD/hour. If the initial glycemia is higher than 33,3 mmol/lл insulin dose in first hour is increased till 16 OD. In case of decreasing of sugar level on 25-50 % from the initial level the speed of introduction of insulin is correspondingly decreased on 25-50 %. If glycemia is lower than 16,6 mmol/l insulin should be introduced with the speed of 4 OD/hour. In case of decreasing of sugar level lower than 11 mmol/l, it is recommended to transfer to subcutaneous introduction of the drug every 6-8 hours.

• Glycemia should not be decreased faster than 5 mmol/l/hour, otherwise it is possible to promote brain edema. The level of glycemia should be examined every 30-60 minutes.

2. Elimination of dehydration and hypovolemiadehydration and hypovolemia: intravenous dropping introduction of liquids: during 1st hour 1 l of 0,9 % NaCl (better – Ringer’s solution) is introduced, during the next 2 hours – 500 ml of 0,9 % NaCl each hour, and after not more than 300ml/hour. In case of decreasing of glycemia level lower than 14 mmol/l, 0,9 % NaCl should be substituted by 5-10 % glucose solution

3. Acidosis correctionAcidosis correction – solution of sodium hydrocarbonate (if pH lower than 7,1)

4. Correction of electrolyte disordersCorrection of electrolyte disorders: after 2 hours from beginning of treatment intravenous dropping introduction of КСІ dosed 2 g/hour should be started under the constant control of potassiumemia.

5. Symptomatic treatmentSymptomatic treatment: of correction of blood pressure only introduction of mesatone is possible, since other adrenomimetics stimulate glycogenolysis and increase sugar level in blood.

COMLICATIONS OF INSULIN COMLICATIONS OF INSULIN THERAPY OF DIABETESTHERAPY OF DIABETES

• Hypoglycemic comaHypoglycemic coma • allergyallergy• lipodystrophylipodystrophy• resistanceresistance to the drugto the drug ( (daily dose of insulin daily dose of insulin

grows to grows to 200 200 U and moreU and more) ) it is causedit is caused: : а) а) production of antibodies towards insulinproduction of antibodies towards insulin, , bb)) increasing of binding with plasma proteins increasing of binding with plasma proteins, , cc) ) decreasing of receptors’ sensitivity to insulindecreasing of receptors’ sensitivity to insulin, , dd) ) obesityobesity,,ee) ) increasing of contrainsular hormones levelincreasing of contrainsular hormones level,,ff) ) pseudoresistance pseudoresistance – – injecting the drug into places of lipodystrophyinjecting the drug into places of lipodystrophy

((considerable worsening of drug absorptionconsiderable worsening of drug absorption). ).

TREATMENT OF TREATMENT OF HYPOGLYCEMIC COMAHYPOGLYCEMIC COMA

• Intravenous bolus introduction of Intravenous bolus introduction of 20-50 20-50 ml ofml of 40 % 40 % glucose (dextrose) solutionglucose (dextrose) solution. .

• If the condition doesn’t improve, afterIf the condition doesn’t improve, after 10-20 10-20 minutes minutes the injection should be repeatedthe injection should be repeated. .

• In case of absence of effect intravenous dropping In case of absence of effect intravenous dropping infusion of infusion of 5 % 5 % glucose solutionglucose solution should be started should be started. .

• Correction of blood pressure and stimulation of Correction of blood pressure and stimulation of glycogenolysisglycogenolysis – – adrenalinadrenalin hydrochloride hydrochloride. .

• Prophylaxis and treatment of brain edemaProphylaxis and treatment of brain edema – – mannitmannit, , glucocorticosteroidsglucocorticosteroids..

SYNTHETIC ANTIDIABETIC SYNTHETIC ANTIDIABETIC PREPARATIONSPREPARATIONS

(taken orally)(taken orally)

Derivatives of sulfonilureaDerivatives of sulfonilurea – – 4 4 generationsgenerations

ІІ ( (appeared in theappeared in the 50- 50-ss) – ) – chlorpropamidchlorpropamid, , butamidbutamid, , bucarbanbucarban; ;

ІІІІ ( (introduced afterintroduced after 1967) – 1967) – glybenclamidglybenclamid ((maninilmaninil); );

ІІІІІІ – – glymeperidglymeperid ( (amarylamaryl););

ІУІУ – – repaglynidrepaglynid. .

Possible mechanism of hypoglycemic action of derivatives of sulfonilurea

butamid, chlorpropamid

Block of ATP-dependent К+ -canals of -cells

Depolarization of membranes of -cells

Opening of potential-depending Са 2+ -canals of -cells

Entering of Са 2+ into -cells

Secretion of insulinSecretion of insulin

Mechanism of action of sulfonilurea Mechanism of action of sulfonilurea derivatiesderivaties

• Blockade of ATP-depended Blockade of ATP-depended КК+ + - - canalscanals of of --cells of cells of Langergan’s islesLangergan’s isles – – depolarization of depolarization of --cells cells membranesmembranes – – opening of potential-depending opening of potential-depending СаСа2+2+--canalscanals – – increasing of increasing of СаСа2+2+ income intoincome into --cellscells – – activation of insulin excretionactivation of insulin excretion..

• Similar mechanism if responsible for secretion of Similar mechanism if responsible for secretion of insulin under the influence of glucoseinsulin under the influence of glucose. . But in this But in this case the signal for closing of ofcase the signal for closing of of К К ++--canals is canals is increasing of correlation ATPincreasing of correlation ATP//ADPADP, , which is caused which is caused by intracellular metabolism of glucose. Therefore by intracellular metabolism of glucose. Therefore derivatives of sulfonilurea imitate signal of increased derivatives of sulfonilurea imitate signal of increased concentration of sugar in bloodconcentration of sugar in blood..

Indications for administration of Indications for administration of drugsdrugs – – derivatives of derivatives of

sulfonilureasulfonilurea diabetes mellitus ofdiabetes mellitus of ІІ ІІ typetype, , ifif: : а)а) all the possibilities of diet therapy are used all the possibilities of diet therapy are used

upup

bb)) diabetes is diagnosed after the age ofdiabetes is diagnosed after the age of 40; 40;

cc)) patient suffers from diabetes no more than patient suffers from diabetes no more than 10 10 yearsyears; ;

dd)) there are no complications and pregnancythere are no complications and pregnancy..

Classification of biguanidsClassification of biguanids

1.1. PhenilethylbiguanidsPhenilethylbiguanids ( (phenphorminphenphormin););

2.2. ButhylethylbiguanidsButhylethylbiguanids ( (buphormin-buphormin-glibutidglibutid););

3.3. Dimethylbiguanids Dimethylbiguanids ((methphorminmethphormin – – glucophageglucophage).).

Mechanism of action of Mechanism of action of biguanidsbiguanids

Mechanism of sugar-decreasing action of biguanidsMechanism of sugar-decreasing action of biguanids – – influence of peripheral tissuesinfluence of peripheral tissues: :

1.1. increasing of action of endogen insulin due to increasing increasing of action of endogen insulin due to increasing of quantity and sensitivity of insulin receptorsof quantity and sensitivity of insulin receptors; ;

2. 2. decreasingdecreasing of absorption of glucose in intestines, of absorption of glucose in intestines, blockade of gluconeogenesisblockade of gluconeogenesis; ;

3. 3. increasingincreasing of synthesis of glycogen in liverof synthesis of glycogen in liver; ; 44. . increasingincreasing of glucose metabolism till stage of lactate in of glucose metabolism till stage of lactate in

musclesmuscles..

Biguanids depress lipogenesis and stimulate lipolysis, Biguanids depress lipogenesis and stimulate lipolysis, which leads to body weight loss in obese patientswhich leads to body weight loss in obese patients

Inhaled InsulinInhaled Insulin „ „Sanofi-Aventis-PfizerSanofi-Aventis-Pfizer””

• powderpowder

• before every meal, small onset before every meal, small onset

• for diabetes type 2, which is not for diabetes type 2, which is not controlled by peroral hypoglycemic controlled by peroral hypoglycemic drugs drugs

• as additional therapy for type 1 as additional therapy for type 1 diabetes treatmentdiabetes treatment

Sites of Action of Drugs Used to Treat Sites of Action of Drugs Used to Treat DiabetesDiabetes

Types of Glucose-Elevating Agents

• Diazoxide (Proglycem)– Can be taken orally

• Glucagon (GlucaGen)– The hormone produced by the alpha cells of

the pancreas to elevate glucose levels – Can be given only parenterally; preferred for

emergency situations

Hormonal preparations Hormonal preparations of thyroid glandof thyroid gland

Actions of the Thyroid GlandActions of the Thyroid Gland• Produces two thyroid hormones using Produces two thyroid hormones using

iodine found in the diet: iodine found in the diet: – Tetraiodothyronine or Tetraiodothyronine or levothyroxinelevothyroxine (T(T44))

– Triiodothyronine or Triiodothyronine or liothyronineliothyronine (T (T33))

• Removes iodine from the blood, Removes iodine from the blood, concentrates it, and prepares it for concentrates it, and prepares it for attachment to tyrosine, an amino acidattachment to tyrosine, an amino acid

Thyroid Control of Hormone LevelsThyroid Control of Hormone Levels

Regulation of thyroid hormones synthesisRegulation of thyroid hormones synthesis

Functions of Thyroid HormonesFunctions of Thyroid Hormones

• Regulate the rate of metabolismRegulate the rate of metabolism• Affect heat production and body temperatureAffect heat production and body temperature• Affect oxygen consumption, cardiac output, Affect oxygen consumption, cardiac output,

and blood volumeand blood volume• Affect enzyme system activity Affect enzyme system activity • Affect metabolism of carbohydrates, fats, and Affect metabolism of carbohydrates, fats, and

proteinsproteins• Regulate growth and developmentRegulate growth and development

Types of Thyroid Dysfunction• Hypothyroidism

– Underactivity

• Hyperthyroidism– Overactivity

Causes of Hypothyroidism• Absence of the thyroid gland

• Lack of sufficient iodine in the diet to produce the needed level of thyroid hormone

• Lack of sufficient functioning thyroid tissue due to tumor or autoimmune disorders

• Lack of TRH related to a tumor or disorder of the hypothalamus

Replacement Hormone Products for Replacement Hormone Products for Treating HypothyroidismTreating Hypothyroidism

• LevothyroxineLevothyroxine (Synthroid, Levoxyl, Levo-T, Levothroid): Synthetic salt of T4

• Thyroid desiccated (Armour Thyroid and others): Prepared from dried animal thyroid glands and contains both T3 and T4

• LiothyronineLiothyronine (Cytomel): Synthetic salt of T3

• Liotrix (Thyrolar): Synthetic preparation of T4 and T3 in a standard 4:1 ratio

Drugs of thyroid hormonesDrugs of thyroid hormones

Name Contents, origin Onset Duration of action

Way of introduc-tion

Thyreoidine Thyreoidine (Thyroxin(Thyroxin + + threeiodthyronin)threeiodthyronin) extract from extract from thyroid glandthyroid gland

2-3 2-3 daysdays 3-4 3-4 weeksweeks OrallyOrally

Threeiodthyronin Threeiodthyronin (liothyronin) (liothyronin)

Synthetic Synthetic 4-8 4-8 hourshours 8-10 8-10 daysdays Orally Orally

Levothyroxin-Levothyroxin-sodium sodium ((L-L-thyroxin-sodiumthyroxin-sodium))

Synthetic Synthetic 3-4 3-4 daysdays ((max.max. 8-10 8-10 daysdays))

2-4 2-4 weeksweeks Orally Orally

Focus on the Replacement Hormone Focus on the Replacement Hormone Prototype: LevothyroxinePrototype: Levothyroxine

• Indications: Replacement therapy in hypothyroidism; pituitary TSH suppression in the treatment of euthyroid goiters, management of thyroid cancer; thyrotoxicosis in conjunction with other therapy; myxedema coma

• Actions: Increases the metabolic rate of body tissues, increasing oxygen consumption, respiration, and heart rate; the rate of fat, protein, and carbohydrate metabolism; and growth and maturation

• PO route: Onset slow; peak 1–3 weeks• IV route: Onset 6–8 h; peak 24–48 h• T½: 6–7 days; metabolized in the liver and excreted in

the bile

LL -- thyroxinthyroxin

ThyreocombThyreocomb((thyroxinthyroxin + + threeiodthyroninthreeiodthyronin))

Thyreotom Thyreotom ( (thyroxinthyroxin + + threeiodthyroninthreeiodthyronin))

Hyperthyroidism• Definition

– Excessive amounts of thyroid hormones are produced and released into the circulation

• Cause– Graves’ disease

• Signs and symptoms– Increased body temperature, tachycardia, thin

skin, palpitations, hypertension, flushing, intolerance to heat, amenorrhea, weight loss, and goiter

Antithyroid Agents• Thioamides

– Propylthiouracil (PTU) – Methimazole (Tapazole)

• Iodine solutions

Adverse Effects of Iodine Solutions

• Hypothyroidism

• Iodism (metallic taste and burning in the mouth, sore teeth and gums, diarrhea, cold symptoms, and stomach upset)

• Staining of teeth

• Skin rash

• Development of goiter

Antithyroid drugsAntithyroid drugs

1)1) Depression of production of TTHDepression of production of TTH -- iodineiodine -- diiodithyrosine diiodithyrosine ( (dithyrinedithyrine))2)2) Depression of synthesis of hormones in thyroid glandDepression of synthesis of hormones in thyroid gland -- mercasolilmercasolil -- propilthiouracyl propilthiouracyl

3)3) Disturbance of absorption of Disturbance of absorption of ІІ22 by thyroid glandby thyroid gland -- potassium perchlorate potassium perchlorate

4)4) Destroying cells of thyroid gland follicles Destroying cells of thyroid gland follicles -- radioactive iodine radioactive iodine (І (І131131) )

Calcium Control in the BodyCalcium Control in the Body

Actions of Parathormone (PTH)• Stimulation of osteoclasts or bone cells to

release calcium from the bone

• Increased intestinal absorption of calcium

• Increased calcium resorption from the kidneys

• Stimulation of cells in the kidney to produce calcitriol

Parathyroid Dysfunction• Hypoparathyroidism

– The absence of parathormone– Most likely to occur with the accidental

removal of the parathyroid glands during thyroid surgery

• Hyperparathyroidism – The excessive production of parathormone– Can occur as a result of parathyroid tumor or

certain genetic disorders

Hormonal preparations Hormonal preparations of steroid structureof steroid structure

Natural hormones of adrenal cortex

Glucocorticosteroids

hydrocortisone (cortisole)corticosterone

cortisone11-dehydrocorticosterone

Mineral corticosteroids

aldosteronedesoxycorticosterone

11-desoxy-17-oxy-corticosterone

Hormones with sexual activity

androsteroneandrostendione

estroneprogesterone

Hypothalamus-adrenal axis

Hypothalamus-hypophysis-epinephral system

HypothalamusHypothalamusCRH Somatostatin GRH TRH PRH PIH GnRHCRH Somatostatin GRH TRH PRH PIH GnRH

Anterior pituitaryAnterior pituitaryGrowth hormone ACTH TSH FSH Growth hormone ACTH TSH FSH LH (male) LH (female) ProlactinLH (male) LH (female) Prolactin

Peripheral endocrine glandsPeripheral endocrine glandsAdrenal cortex Thyroid Gonads LiverAdrenal cortex Thyroid Gonads Liver

Feed-back mechanismFeed-back mechanism

Properties of glucocorticosteroides used in

clinics

• Anti-inflammatoryAnti-inflammatory

• Immune-suppressiveImmune-suppressive

• Anti-allergicAnti-allergic

• Anti-shockAnti-shock

• Anti-toxicAnti-toxic

Anti-inflammatory action of GCS

• Nonspecific inflammation

• Auto-immune component

• Hyperergic character

• Therapy of despair

Mechanism of anti-inflammatory action of GCS

GCS

activation of lipomoduline

decreasing of activity of phospholipase А2

slowing down of arachidonic acid metabolites production

(prostaglandins, leucotriens, thromboxan А2)

stabilization of cellular and

lyzosomalmembranes

decreasing of leucocytes’

migration processes, depression of

phagocytes activity

decreasing of capillaries’ wall permeability

depression of histamine, serotonin, bradykinine releasing

Administration of GCS• Insufficiency of adrenal cortexInsufficiency of adrenal cortex • Rheumatoid illnesses Rheumatoid illnesses ((rheumatoid arthritis, rheumatoid arthritis,

rheumatism, system red lupus etc.rheumatism, system red lupus etc.))• Chronic active hepatitisChronic active hepatitis• Bronchial asthmaBronchial asthma • Ulcerative colitisUlcerative colitis• Nephritic syndromeNephritic syndrome• Auto-immune hemolytic anemiaAuto-immune hemolytic anemia• Shock and collapse of any etiologyShock and collapse of any etiology• Brain, lungs, larynx edemaBrain, lungs, larynx edema• Acute allergic reactionsAcute allergic reactions • Transfusion reactionsTransfusion reactions• Heavy infectionsHeavy infections ( (hiding behind the etiotropic drugshiding behind the etiotropic drugs!)!)• Liver diseasesLiver diseases

Doses and terms of GCS therapy

Situation Daily dose Terms of treatment

Acute casesAcute cases ( (shock, shock, collapse, brain, lungs collapse, brain, lungs edema, septic shock, edema, septic shock, asthmatic condition etc.asthmatic condition etc.))

200-500-200-500-800-1000 800-1000 mg mg i.v.i.v.

1-3 1-3 daysdays

Subacute and acute Subacute and acute attacks of chronic attacks of chronic processesprocesses ( (rheumatoid rheumatoid diseases, ulcerative colitis, diseases, ulcerative colitis, bronchial asthma etc.bronchial asthma etc.))

20-50 20-50 mgmg((rarely tillrarely till 200 200 mgmg))

4-6 4-6 weeksweeks--several several monthsmonths

Primary and secondary Primary and secondary insufficiency of adrenal insufficiency of adrenal cortexcortex

2,5-10 2,5-10 mgmg life-longlife-long

Hydrocortisone acetate

Prednisolone

Prednisolone

Prednisolone

Becotide = Beclometh(beclomethasone dipropionate)

Kenalog(triamcinolone acetonide)

Kenalog(triamcinolone acetonide)

Fluocinar – Sinaflan – Sinalar(Fluocinole acetonide)

Dexamethasone

Dexamethasone

Dexamethasone

Lorinden A: flumethasone pivalate

(locacorten) + neomycin

Steroid diabetesSteroid diabetesimmune-suppressionimmune-suppressiondepression of resistance towards any infectionsdepression of resistance towards any infections atrophy of musclesatrophy of muscleshypopotassiumemiahypopotassiumemiapeptic ulcerspeptic ulcersdisturbance of regenerationdisturbance of regenerationosteoporosis, delay of growthosteoporosis, delay of growthmatronismmatronism ( (“buffalo hump”, “moonlike face” etc.)“buffalo hump”, “moonlike face” etc.)retention ofretention of NaNa++ , , HH22o edemao edemahypertensionhypertension hypercoagulation of bloodhypercoagulation of bloodchanges of psychical conditionschanges of psychical conditions disturbance of menstrual cycledisturbance of menstrual cyclehypothalamus-pituitary-epinephral insuffciencyhypothalamus-pituitary-epinephral insuffciency

Izenko-Cushing’s syndrome

Complications of GCS-therapyComplications of GCS-therapy

Controls and Actions of the Adrenal Glands

MINERALOCORTICOIDSDesoxycorticosterone acetate - DOXA

• Mode of actionMode of action

Acts on kidney tubules: causes the reabsorption of Acts on kidney tubules: causes the reabsorption of sodium and water, decreases the reabsorption of sodium and water, decreases the reabsorption of potassium,potassium,

regulates fluid-electrolyte metabolism, increases AP, regulates fluid-electrolyte metabolism, increases AP, enhances muscle workenhances muscle work

• AdministrationAdministration

For chronic adrenal insufficiency (Addison’s disease), For chronic adrenal insufficiency (Addison’s disease), myasthenia, adynamiamyasthenia, adynamia

• Side effectsSide effects

edema, AP increasing, pulmonary edema, cardiac edema, AP increasing, pulmonary edema, cardiac insufficiencyinsufficiency

Drugs of female sex Drugs of female sex hormoneshormones

Estrogens Estrogens

estron(oil solution of folliculin)estradiolethynilestradiol(microfollin)synestrol

Gestagens Gestagens

progesteroneoxyprogesterone caproatealilestrenol (turinal)

Estrogens

• UsesUses– Hormone replacement therapy (HRT)– Palliative and preventive therapy during

menopause

• Actions Actions – Protecting the heart from

atherosclerosis– Retaining calcium in the bones– Maintaining the secondary female sex

characteristics

Sites of Action of the Estrogens

Administration of drugs of female sex hormones

estrogensestrogens

1) Genital hypoplasia, primary and secondary amenorrhea2) Sexual underdevelopment of women3) After ovary-ectomia4) Climacteric disorders 5) Lactation depression6) Weak labor activity(estrogen background)7) Prostate cancer of men, breast cancer of women after the age of 608) A part of contraceptive agents

Effects of Progesterone on the Body

• Decreased uterine motility• Development of secretory

endometrium• Thickened cervical mucus• Breast growth• Increased body temperature• Increased appetite• Depressed T-cell function• Anti-insulin effect

Administration of gestagens

1) miscarriage, habitual abortion

2) dysfunctional uterus bleedings, algomenorrhea

3) as component of contraceptives

4) Climacteric disorders5) As part of fertility programs

6) Treat specific cancers with specific receptor site sensitivity

Hormonal contraceptivesHormonal contraceptives

1)1) combined estrogen-gestagencombined estrogen-gestagen aa)) monophased monophased ((bisecurin, non-ovlon, rigevidonbisecurin, non-ovlon, rigevidon, ,

marvelon, demulenmarvelon, demulen)) bb) ) double-phaseddouble-phased ( (anteovin, neo-eunominanteovin, neo-eunomin))

cc) ) triple-phasedtriple-phased ( (tri-regol, trisistontri-regol, trisiston))2)2) monohormonal gestagenmonohormonal gestagen ( (mini-pillimini-pilli))

exluton, ovret, continuinexluton, ovret, continuin3)3) postcoital hestagenpostcoital hestagen ( (postinorpostinor))

4)4) depot-contraceptivesdepot-contraceptives - - of prolonged actionof prolonged action norplantnorplant ( (levonorgestrellevonorgestrel))

depot-proveradepot-provera ( (medroxyprogesterone acetatemedroxyprogesterone acetate))

hypertension hypertension hypercoagulationhypercoagulationdyspeptic disordersdyspeptic disorders ( (nausea, vomitingnausea, vomiting))migraine migraine depressiondepressionobesityobesitycholestatic jaundicecholestatic jaundicebreast cancer, cancer of uterus cervixbreast cancer, cancer of uterus cervixischemic heart diseaseischemic heart diseasemyocardium infarctionmyocardium infarctionstrokestrokeembryotoxic and teratogenic actionembryotoxic and teratogenic action

thrombo-emboliathrombo-embolia

Complications in case of administration ofhormonal contraceptives

Focus on the Fertility Drug Prototype: Clomiphene

• Indications: Treat ovarian failure in patients with normal liver function and normal endogenous estrogens; unlabeled use: treat male sterility

• Actions: Binds to estrogen receptors, decreasing the number of available estrogen receptors, which gives the hypothalamus the false signal to increase FSH and LH secretion, leading to ovarian stimulation

• PO route: Onset 5–8 days; duration 6 weeks

• T½: 5 days, with hepatic metabolism and excretion in the feces

Abortifacients

• UseUse– Evacuate the uterus by stimulating

intense uterine contractions

• TypesTypes– Carboprost (Hemabate)– Dinoprostone (Cervidil, Prepidil Gel,

Prostin E2)– Mifepristone (RU-486, Mifeprex)

Androgens and Their Indications

• Testosterone (Duratest, Testoderm, others) – Hypogonadism; breast cancer

• Danazol (Danocrine)– Block the release of FSH and LH in women

• Fluoxymesterone (Halotestin)– Hypogonadism; breast cancer

• Testolactone (Teslac)– Breast cancers

ANABOLIC STEROIDSPhenobolinum, Retabolil, Methandrostenolonum

PHARMACOLOGICAL EFFECTSPHARMACOLOGICAL EFFECTS- Stimulation of protein synthesis- Depression of phosphor and Ca++ excretion- Increase of bones, muscles and parenchymatous

organs mass- Stimulation of regeneration

ADMINISTRATIONADMINISTRATION- Aplastic anemia (bone marrow suppression)- Osteoporosis, bone fractures- Exhausted diseases- Prolonged treatment with GCS

COMPLICATIONSCOMPLICATIONS Hepatitis, sexual disorders (impotence), edemas,

masculinization, nausea, vomiting