University:
Michigan State University
Course:
PHM 430 | Human Pharmacology
Academic year:

2021
Views:

81

Pages:

12
Author:

Mugrauauu

Posterior Pituitary Hormones ADH (Vasopressin) & Oxytocin Nonapeptides (9 a.a) Known as neurohormones Synthesized in the hypothalamus Stored in the posterior pituitary → release ? Role as neurotransmitters (V1R’s in CNS) Role of Oxytocin in man is unknown ◼ ADH (Vasopressin) (arginine vasopressin; argipressin) Physiological and pharmacological actions: - Vasoconstriction & ↑ platelet aggregation (V1a receptors) - ↑ reabsorption of H2O from collecting ducts (V2 receptors) - ↑ synthesis of certain clotting factors (VIII, Von Willebrand) (V2 receptors) - ↑ ACTH release (V1b receptors) - Oxytocin-like activity ◼ Factors/Drugs ↑ ADH release: - Hypovolemia, hyperosmolarity, pain, stress, nausea, fever, hypoxia - Angiotensin II - Certain prostaglandins - Nicotine, cholinergic agonists, β-adrenergics - Tricyclic antidepressants - Insulin, morphine, vincristine… ◼ Factors/Drugs ↓ ADH release: - Hypervolemia - Hypoosmlarity - Alcohol - Atrial natriuretic peptide - Phenytoin - Cortisol - Anticholinergics, α-adrenergics, GABA... ◼ Disorders affecting ADH release: A. Excess production (inappropriate ADH secretion) → Dilutional hyponatremia Causes: - Head trauma, encephalitis - Meningitis, oat cell carcinoma… Rx: - Water restriction (Rx of choice) - Hypertonic saline solution - Fludrocortisone → ↑ Na+ blood level - Loop diuretics (Furosemide) - ? ADH antagonists ◼ ADH antagonists - Conivaptan, a non-peptide V1 & V2 R antagonist given IV - Tolvaptan; Lixivaptan & Satavaptan, a nonpeptide orally effective selective V2R antagonists Clinical uses: - Inappropriate ADH secretion - CHF; liver cirrhosis… ◼ B. Deficiency of ADH → Diabetes insipidus (DI)→ polyuria Causes: - Idiopathic DI - Congenital, Familial DI - Hypothalamic surgery, head trauma, malignancies - Gestational DI, overproduction or decreased clearance of vasopressinase Rx: ADH preparations (HRT) ADH preparations: - Natural human ADH (Pitressin) Given I.M, S.C, has short half-life (15 min) - Lypressin (synthetic, porcine source) Given intranasally, I.V, I.M, has short DOA (4hrs) - Desmopressin (synthetic ADH-like drug=analogue) Given intranasally, S.C Most widely used preparation, has long DOA (12 hrs) ◼ - Felypressin (synthetic ADH-like drug) Has strong vasoconstrictor activity Mainly used in dentistry ◼ Clinical uses to ADH: - DI - Nocturnal enuresis - Hemophilia - Bleeding esophageal varices Side effects to ADH preparations: - Allergy - Pallor - Headache, nausea, abdominal pain in ♀’s (oxytocin-like activity) - Anginal pain (coronary artery vasospasm) - H2O intoxication (massive doses) - Gangrene (rare particularly with desmopressin= has great affinity to V2 receptors) ◼

Posterior Pituitary Hormones

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