Diuretics

classification, mechanism of action, complication and uses of diuretics. Diagramatic representation of the mechanism of various ions reabsorption in nephron

1. DIURETICS Revathi Boyina MLR INSTITUTE OF PHARMACY, HYDERABAD

2. Eminence of diuretics Diuretics are the most prescribed drugs. Effective in management of hypertension and cardiovascular diseases. Lesser price raised the use of diuretics since a decade.

3. Diuretics and classification Drugs which cause diuresis that is a net loss of sodium(Na⁺) and water in urine. Diuretics can be classified in two different ways. 1. Based upon the efficacy 2. Based on the site of action

4. Physiology of urine formation and drugs acting on different sites of nephron Classification based on site of action

5. Classification based on the efficacy: 1. High efficacy diuretics / High ceiling diuretics /Loop diuretics (Inhibitors of Na⁺-K⁺-2Cl⁻ co-transport) : (Sulphamoyl derivatives) Furosemide, Torsemide, bumetanide. 2. Medium efficacy diuretics / Thiazide diuretics (Inhibitors of Na⁺-Cl⁻ symport) Benzothiadiazides (thiazides): Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Clopamide. Thiazide like diuretics: Chlorthalidone, Metolazone, Xipamide 3. Weak / adjunctive diuretics Carbonic anhydrase inhibitors : Acetazolamide. Potassium sparing diuretics: i ) Aldosterone antagonist : Spironolactone. ii) Inhibitors of renal epithelial sodium channel: Triamterene, Amiloride. c) Osmotic diuretics: Mannitol, Isosorbide, Glycerol

6. High ceiling ( loop) diuretics (Inhibitors of Na⁺-K⁺-2Cl⁻ co-transport) Furosemide -prototype drug- natriuretic effect and loss of k ⁺ Increase in Ca 2+ excretion as well as increase in Mg 2+ excretion- raises blood uric acid level Absorbed orally -high plasma protein binding-60% bioavailability. Uses

7. THIAZIDE DIURETICS (Inhibitors of Na⁺-Cl⁻ symport) Chlorothiazide - urine rich in chloride ions- alkalosis Increased amount of Na ⁺ in distal nephron, exchanges with K ⁺ and finally increased K ⁺ excretion in urine parallel with natriuretic effect. Reduces blood volume- g.f.r reduce Absorbed orally- high lipid soluble. Used in diabetes insipidus.

8. Complication of high ceiling and thiazide diuretics Hypokalaemia -prevented and by potassium supplements and potassium sparing diuretics. Hyponatreamia Magnesium depletion Hypocalcemia -high ceiling diuretics Hyperuricaemia-long term use Allergic manifestation-rashes, photosensitivity GIT disturbances -Nausea, Vomiting and Diarrhoea. CNS Disturbances -Headache, giddiness, weakness Hearing loss

9. Interactions Thiazides and high ceiling diuretics potentiate antihypertensives Hypokalemia enhances digitalis toxicity , potentiate neuromuscular blocking agents High ceiling diuretics and aminoglycoside antibiotics are both additive ototoxic and nephrotoxicity Cotrimoxazole with diuretics thrombocytopenia Indomethacin and other NSAIDs action of diuretics- inhibition of Prostaglandin synthesis-intrarenal haemodynamic changes-affect salt output Probenecid inhibits both the diuretic at tubular level. Serum lithium levels rise with diuretics.

10. Carbonic anhydrase inhibitors Acetazolamide Decreases the availability of H⁺ to exchange with Na⁺ through Na⁺-H⁺ antiporter in proximal tubule cells and inhibition of HCO ⁻₃ reabsorption. Extrarenal effects -decreases intraocular tension due decreased formation aqueous humour(rich in HCO ⁻₃ )- Glaucoma Raises CO₂ level in the brain lowers pH level in brain- Epilepsy Reduced CSF formation- lowering of CSF and brain pH- Acute mountain sickness. Adverse effects: Acidosis, Drowsiness, Hypersensitivity reactions.

11. POTASSIUM SPARING DIURETICS Spironolactone –aldosterone antagonist- Inhibition of Na ⁺ reabsorption in collecting duct. Used to counteract the K ⁺ loss due to thiazide and high ceiling diuretics in hypertension and CHF. Triamterene and Amiloride - Inhibitors of renal epithelial Na⁺ channel in collecting tubule-decreases the K⁺ excretion Amiloride - potent than triamterene Side effects of spironolactone

12. OSMOTIC DIURETICS Mannitol - Nonelectrolyte of low molecular weight- given in large quantities raises osmolarity of plasma and tubular fluid. Used in increased intraocular and intra cranial tension – Glaucoma , head injury and stroke given i.v as 10-20% solution Isosorbide and glycerol – orally active osmotic diuretics

13. Reference KD. Tripathi Lippincott's Rand and Dale

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