Diuretics

Diuretics

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  DIURETICS Revathi Boyina MLR INSTITUTEOF PHARMACY, HYDERABAD
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  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.
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  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
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  Physiology of urineformation and drugs acting on different sites of nephron Classification based on site of action
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  CLASSIFICATION BASED ONTHE 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) a) Benzothiadiazides (thiazides): Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Clopamide. b) Thiazide like diuretics: Chlorthalidone, Metolazone, Xipamide 3. Weak / adjunctive diuretics a) Carbonic anhydrase inhibitors: Acetazolamide. b) Potassium sparing diuretics: i) Aldosterone antagonist : Spironolactone. ii) Inhibitors of renal epithelial sodium channel: Triamterene, Amiloride. c) Osmotic diuretics: Mannitol, Isosorbide, Glycerol
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  HIGH CEILING (LOOP) DIURETICS (Inhibitors of Na⁺-K⁺-2Cl⁻ co-transport) • Furosemide-prototype drug- natriuretic effect and loss of k⁺ • Increase in Ca2+ excretion as well as increase in Mg2+ excretion- raises blood uric acid level • Absorbed orally -high plasma protein binding-60% bioavailability. • Uses
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  THIAZIDE DIURETICS (Inhibitors ofNa⁺-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.
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  COMPLICATION OF HIGHCEILING 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
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  INTERACTIONS • Thiazides andhigh 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.
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  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.
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  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
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  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
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  REFERENCE • KD. Tripathi •Lippincott's • Rand and Dale