ANTI - DIURETICS
ANTI DIURETIC HORMONE (ADH /AVP / VASOPRESSIN) Synthesized by hypothalamus & released by the posterior pituitary Potent vasopressor
Route of administration : subcutaneous, intramuscular, intranasal Receptors - V1 & V2
V1 receptors have been sub - classified into
V1a (vascular/g.i / hepatic) V1b (pituitary) V2 receptors - collecting duct cells,blood vessels V2 - increases water permeability of the collecting duct V2 - release of blood coagulation factors & secretion of vWf and fac VIII
Mechanism of Action
Mechanism of Action
Mechanism of Action
Vasopressin analogs
Desmopressin (DDAVP) – V2 selective subcutaneous , intranasal Lypressin - intranasal spray – V2 selective Terlipressin
Therapeutic Uses
Desmopressin is the drug of choice for the treatment of central diabetes insipidus (if no response/side effects – Lypressin) Bleeding disorders - von Willebrand's disease (vWD) Primary nocturnal enuresis
Post - lumbar puncture headache
V1 receptor - mediated therapeutic applications
Postoperative ileus / abdominal distension Bleeding esophageal varices – Terlipressin Portal hypertension Acute hemorrhagic gastritis
Drugs that enhance the antidiuretic Effects of vasopressin include
Carbamazepine
Chlorpropamide
Vincristine
Cyclophosphamide
NSAIDs
(Drug induced SIADH)
Inhibitors of vasopressin action include
Lithium Demeclocycline (drug induced nephrogenic DI) Ethanol Lithium appears to reduce V2 receptor mediated stimulation of adenylcyclase
Alternate drugs for the treatment of central diabetes insipidus chlorpropamide, carbamazepine, clofibrate Amiloride is the drug of choice for Li+ induced nephrogenic DI Demeclocycline is the preferred drug in SIADH
Thiazide diuretics are often used to treat nephrogenic DI !
Mechanism of Action ↓d extracellular fluid volume ↓ Activation of compensatory mechanisms ↓ ↑d reabsorption of NaCl in the PCT ↓ reduction of volume delivered to the DCT ↓ less free water can be formed ↓ polyuria is diminished
The selective disruption of the urinary dilution mechanism makes thiazide diuretics effective in disorders characterized by an inappropriately dilute urine
Natriuretic action of thiazides has an important role and that depletion of extracellular fluid volume is essential for Antidiuresis
Adverse Effects Nausea, belching, cramps, urge to defecate Cardiac complications – arrhythmias & decreased cardiac output Peripheral vasoconstriction & gangrene Allergic reactions
Contraindicated in Vascular diseases esp. disease of the coronary arteries