20100225-kbk-controlsystem-Drugs affecting Endocrine Functions.ppt
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Drugs affectingEndocrine Functions
Dep. Farmakologi dan Terapeutik,
Fakultas Kedokteran
Universitas Sumatera Utara
Februari 2010, KBK, FK USU, Medan
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Endocrine System
Endocrine system includes the pituitary,thyroid, parathyroids, pancreas, adrenals, andreproductive organs
Endocrine system secretes hormones directlyinto the bloodstream to function in growth,development, and maintenance of bodyfunctions
Abnormal production of hormones can belife-threatening
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Pituitary Dysfunction
Pituitary can malfunction due to injury,
surgery, tumors, or damage from radiation
Undersecretion or oversecretion
Hypofunction: Hypopituitarism What will occur when there is a complete absence
of pituitary function?
Anterior pituitary hyperfunction most commonly involves ACTH or GH Posterior pituitary hypofunction
Most commonly deficient secretion of ADH
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Drugs Affecting the Pituitary Gland
Anterior Pituitary Gland
1. Conditions treated are those of abnormal
growth, specifically:
* Dwarfism
* Acromegaly
* Gigantism
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Posterior Pituitary Drugs
Two posterior hormones are oxytocin and
antidiuretic hormone (ADH).
Antidiuretic analogues are used to treat diabetes insipidus, nocturnal
enuresis (bedwetting).
can cause vasoconstriction and increased BP.
Other names: Vasopressin (pitressin), desmopressin (stimate),
lypressin (diapid)
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Syndrome of Inappropriate ADH
Secretion
Excess secretion of ADH even with subnormal
serum osmolality
Can not excrete a dilute urine
Retain fluids and develop dilutional hyponatremia
Usually nonendocrine cause
Typical interventions: treat underlying cause and
restrict fluids
May use diuretics (furosemide) is severe Na
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Drugs Affecting the Parathyroid &
Thyroid Glands Parathyroid glands regulate calcium levels.
Hyperparathyroidism, results from a tumor and
treatment is surgical removal of all or part of theglands.
Thyroid gland produces thyroid hormones.
Play a role in regulating growth, maturation,and metabolism. Hyperthyroidism
Hypothyroidism
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Parathyroid Glands
Secrete parathormone in response to lowered serumcalcium levels
Symptoms of parathormone deficiency can includeincreased muscular irritability and psychiatric
disorders Manifestations: Tetany
Latent: numbness, tingling, cramps in extremities, stiff hands and feet
Overt: bronchospasm, laryngeal spasm, carpopedal spasm, dysphagia,seizures, photophobia, cardiac dysrhythmias
Dx: Positive Chvosteksand Trousseaus sign Acute hypoparathyroidismIV parathormone
Chronicdiet high in calcium and low in phosphorus
Oral Ca gluconate, aluminum carbonate, vitamin D
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Acute Hypercalcemic Crisis
Extreme serum calcium elevation
Increased serum calcium levels can be lifethreatening
> 15 mg/dL neurologic, cardiovascular, andrenal symptoms that can be life threatening
Treatment: Rehydration
Diuretics Phosphate treatment
Emergency treatment to lower calcium
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Thyroid Dysfunction
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Hypothyroidism
Treatment is aimed at thyroid hormone
replacement.
Prototype drug: levothyroxine (Synthroid)
No significant side effects in therapeutic
doses.
Overdose could lead to thyrotoxicosis or
thyroid storm.
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Goiter
Not common in developed countries.
AKA Hashimotos disease
Chronic autoimmune disease Treatment is aimed at supplementing the
inadequate iodine.
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Hyperthyroidism
Typically a result of tumors
Most common cause is Graves Disease
Treatment is typically surgical removal of allor part of the gland.
Radioactive iodine may be given
Propylthiouracil(PTU), may be given alone orin conjunction with radiation
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Antithyroid Hormones
Inhibits the synthesis of thyroid hormones by
decreasing iodine use; does not inactivate or
inhibit T3 or T4
Commonly used to treat hyperthyroidism
May increase the effect of anticoagulants
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Drugs Affecting the Adrenal Cortex
Adrenal cortex secretes 3 classes of hormones:
1. Glucocorticoids
2. Mineralocorticoids3. Androgens
Two diseases associated with the adrenal cortex:1. Cushings Disease
2. Addisons disease
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Cushings Disease
Treatment is typically surgical.
Pharmacologic intervention with a
antihypertensives:1. Spironolactone (Aldactone)
2. ACE inhibitorsCaptopril (Capoten)
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Drugs Affecting the Pancreas
Insulin Preparations
Three Sources:
1. Beef
2. Pork
3. Human
Differprimarily in their onsetand duration
of action and incidence of allergic reaction.
Preparations may be short acting,intermediate acting or long acting.
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Oral Hypoglycemic Agents
Used to stimulate insulin secretion from
the pancreas is patients with NIDDM.
Four Pharmacologic classes:1. Sulfonylureas
2. Biguanides
3. Alpha-glucosidase inhibitors
4. Thiazolidinediones
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Hyperglycemic Agents
Two agents:
1. Glucagon
2. Diazoxide (proglycem) Increase blood glucose levels.
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Glucagon
Given IM when IV live is unobtainable
Converts glycogen stores into glucose
Side effects: N/V, allergic reactions (rare)
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Diazoxide
Inhibits insulin release
Typically used for patient with
hyperinsulin secretion from pancreatictumors
Not indicated for treating diabetes-
induced hypoglycemia
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D50 (Dextrose 50%)
Sugar solution given intravenouslyfor acutehypoglycemia.
Primary side effect is local tissue necrosis if infiltrationoccurs
Action Rapidly increases serum glucose levels
Provides short-term osmotic diuresis
Indication Coma of unknown origin
Hypoglycemia
Status Epilepticus
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DEXTROSE 50%
Contraindications Intracranial hemorrhage
Delirium tremens
Use with caution in acute alcoholism - ineffective without
thiamine; may make thiamine deficiency more severe
Severe pain (paradoxical excitement may occur)
Know or suspected CVA unless hypoglycemia is
documented
Adverse reaction Extravasation leads to tissue necrosis
Incompatible Reactions Sodium bicarbonate
Coumadin
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GLUCOSE
Actions
A quickly absorbed form of glucose to increase
blood glucose levels
Indications Hypoglycemia
Conscious patients
Contraindications
Decreased level of consciousness Nausea/vomiting
Precautions
Assure that the airway is patent
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Glucagon
Insulin antagonist used in the management ofsevere hypoglycemia Increases blood glucose levels by increasing the
breakdown of glycogen to glucose and inhibitsglycogen synthesis
Mechanism of Action: binds on Glucagon receptors(GPCR type) on
hepatocytes increased cAMP PK A glycogen phosphorylase release of glucose from
glycogen Metabolic effects:
catabolic hormone - increased glycogenolysis andgluconeogenesis result in increased plasma glucose
levels
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GLUCAGON
Actions Protein secreted by the alpha cells of the pancreas (islets
of Langerhans)
Causes a breakdown of stored glycogen to glucose
(glycogenesis); increases circulating blood glucose Unknown mechanism of stabilizing cardiac rhythm in beta-blocker overdose
Positive inotropic and chronotropic
Decreases GI motility and secretions, pancreatic
secretions, and blood pressure Incompatible/Reactions
Incompatible in solution with most other substances
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GLUCAGON
Indications Hypoglycemia
Beta-blocker overdose
Contraindications
Hyperglycemia Known hypersensitivity
Adverse Reactions Hypersensitivity (protein-based drug)
Nausea/vomiting Precautions
Caution with administration to patients with a history ofcardiovascular or renal disease
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Proglycem
Hyperglycemic agent that may be used in the
treatment of hypoglycemia associated with
hyperinsulinism or other causes
Inhibits pancreatic-insulin release
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THIAMINE
Actions Required for carbohydrate metabolism
Deficiency leads to anemia, polyneuritis,
Wernickes encephalopathy, cardiomyopathy
Administration may reverse symptoms ofdeficiency, but effects are dependent upon
duration of illness and severity of disease
Indications
Coma of unknown origin, especially if alcohol may
be involved
Delirium tremens
Other thiamine deficiency syndromes
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THIAMINE
Contraindications Known hypersensitivity
Adverse Reactions Rare
Incompatible/Reactions Alkaline solutions
Barbiturates
Bicarbonate Cephalosporins
Other antibiotics
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INSULINActions Protein secreted by beta cells of the Islets of
Langerhans Responsible for promoting the uptake of glucose by
the cells (muscle, cardiac, CNS, and all other tissue)
Necessary for carbohydrate, fat and proteinmetabolism
Converts glycogen to fat Allows glucose storage in the liver
Promotes fat and protein synthesis whileantagonizing fat breakdown Produces intracellular shift of potassium and
magnesium to reduce elevated serum levels of thoseelectrolytes
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INSULIN
Indications Rarely used in the field - blood glucose levels are necessary
before administering in an emergency situation
In-hospital use: diabetic ketoacidosis or other
hyperglycemic state Hyperkalemia
Contraindications / Adverse Reactions Hypoglycemia
Hypokalemia Incompatible/Reactions
Incompatible in solution with all other drugs
Antagonizes actions of epinephrine, steroids, estrogens,
thyroid hormones, diazoxide, dilantin
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Insulin receptors
Insulin receptors are cell surface
receptors with protein kinase activity
They are responsible for bothphysiological and pharmacological
action of insulin and its analogues
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INSULIN
Notes Usually refrigerated
Oral hypoglycemics, such as Orinase,
Diabinese and Dymelor, are not substitutesfor insulin, they stimulate the release of
insulin from a sluggish pancreas
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Adrenal Gland Dysfunction:
Pheochromocytoma
Tumor of the adrenal gland
Usually benign
Peak incidence between 40 and 50
Symptoms triad: headache, diaphoresis andpalpitations
Hypertension and cardiac disturbances common
Acute, unpredictible onset with gradual resolution ofsymptoms
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Adrenal Insufficiency
Adrenal cortex function
is inadequate to meet
the needs for cortical
hormones Primary: Addisons
Secondary
What is the most
common cause of Acute
Adrenal Insufficiency?
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Adrenal Crisis
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Adrenal Crisis
Medical Management
Immediate
Reverse shock
Restore blood circulation
Antibiotics if infection
Identify cause Supplement glucocorticoids during
stressful procedures or significant illness
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Cushings Syndrome
Excessive adrenocortical
activity
Most often due to
corticosteroid use Overnight
dexamethasone
suppression test
Indicators: Na+
glucose K+
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Cushings Syndrome
Medical Management
Pituitary tumor
Surgical removal
radiation
Adrenalectomy
Adrenal enzyme inhibitors
Metyrapone, glutethimide, ketoconzole
attempt to reduce or taper corticosteroid
dose
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Primary Aldosteronism
Profound K+ and H+
ions, pH and HCO3
Near normal or Na
Universal sign: HTN Dx:
Measurement of aldosterone
excretion rate after salt
loading Renin-aldosterone
stimulation test and bilateral
adrenal venous sampling
Symptoms:
Muscle weakness
Cramping
Fatigue Nonacid urine
Polyuria
serum osmolality
Polydypsia
Arterial HTN
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Primary Aldosteroninsm
Medical Management
Surgical removal
Spironalactone for persisitent HTN
Monitor for fluctuations in adrenal hormones
Corticosteroids, fluids, agents to maintain BP and
prevent complications
Maintain normal serum glucose
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Common endocrine complications
type 2 (NIDDM) diabetes,
hypertension,
dyslipidaemia, and cardiovascular diseases including AMI, AP,
PVD & stroke.
Why are these now considered
complications of endocrine disorders?
b l d f
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Metabolic dysfunction
drug-induced hyperprolactinemia
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