DIURETICS - CARDIOVASCULAR DRUGS ( PART 7/7) LIPINCOTT AND KADZUNG REVIEW CHAPTES

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 Thiazide Diuretics

Sulphonamide derivative..related in structure to Carbonic Anhydrase….partly depend on renal PG synthesis

Act on DISTAL CONVULATED TUBULE….called Ceiling Diuretics b/c increase in dose above normal dose not increase Diuretic response

Diuretic thiazide potassium sparing and alodsterone antagonist

MOA=Act on distal tubules...inhibit Na+/CI- Cotransporter…decrease Reabsorption of Na+….increased Excretion of Na+ & CI-..Loss of K+..Loss of Mg++..decreased excretion of Ca++…reduced peripheral Vascular Resistance

T.E=used in Hypertension, HF (decrease extracellular volume), Hypercalciuria,Diabetes Insipidus……

excreted thhroughorganic acid secretary sys of kidney

S.E=Hypokalemia, Hyonatremia, HyperUricemia (by decreasing excretion of uricacid from organic acid secretary sys), Volume depletion, Hypercalcemia, Hyperglycemia,Hyperlipidemia, Hypersensitivity

Loop Diuretics

Act on ASCENDING LOOP OF HENLE….high Efficacy…Ethacrynic acid has Steeper

Dose Response Curve….Bumetanide more potent

MOA=inhbit Na+/K+/2CI-Cotransport in ascending loop of henle…reasabsorption of these ions decreases…20-30% reabsorption of NaCI..increase excretion of Ca++…decreased Renal Peripheral Vascular Resistance…increased renal blood flow…increase PG synthesis

T.E=DOC in Acute Pulmonary Edema of HF…used in Hypercalcemia & Hyperkalemia

S.E= ototoxicity, Hyperuricemia, Acute Hypovolemia, Hypokalemia, Hypomagnesemia,

Potassium-Sparing Diuretics

Act on Collecting Tubules‟…

Spiranolactone & Eplerenoone= Aldosterone Antagonist…Spiranolactone antagonize Aldosterone at intracellular receptor sites…..Spiranolactone-receptor complex inactive... prevent Translocation...cannot bind to DNA…fail to produce protein in response to Aldosterone…prevent Na+ reabsorption...K+ & H+ retention

T.E=Diuretic, in Sec. HyperAldosteronism, HF ….Patient with Addisson disease no diuretic effect bcz no circulating level of Aldosterone

S.E=peptic ulcer, gynecomastia, menstrual irregularities, lethargy,

Triamtrene & Amiloride= block Na+/K+ exchange...Na+ excretion…K+ retention

S.E= leg cramp, increased blood urea nitrogen, uric acid & K+ retention

Carbonic Anhydrase Inhibitors

Act on Proximal Tubule

Acetzolamide= inhibit Crbonic Anhydrase…Carbonic Anhydrase convert CO2 +H2O=H2CO3….Ionize into H+ & HCO3-1…inhibit exchange of Na+ with H+…HCO3- excretion…PH,Na+, K+ excretion….

T.E= treatment of Glaucoma, mountain sickness

S.E= Metabolic acidosis, renal stone, paresthesia,

Osmotic Diuretics

Mannitol & Urea=carry water with them .used in patients with increased intracranial pressure, Acute renal failure, Shock, drug toxicity, trauma……

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