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Diuretics

Diuretics. Why do we want to know about diuretics?. What do kidneys do? What can go wrong? Interventions that can be used how do they work? Effects, side effects. Functions of the kidney?. Excretion of waste products regulation of salt and electrolyte content

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Diuretics

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  1. Diuretics

  2. Why do we want to know about diuretics? • What do kidneys do? • What can go wrong? • Interventions that can be used • how do they work? • Effects, side effects

  3. Functions of the kidney? • Excretion of waste products • regulation of salt and electrolyte content • and volume of extra -cellular fluid • acid -base balance

  4. How? • Several hundred litres of plasma filtered/day • filtrate - very little protein/protein bound substances • 99% of sodium is reabsorbed, some substances secreted • 1.5 litres voided as urine • Diuretics increase salt and water excretion

  5. Why diuretics? • important group of drugs employed for their effects on the kidney to enhance salt and water excretion (only when needed) • when used: heart failure, other causes of salt and water retention (renal failure, liver failure), hypertension

  6. Variety of compounds with diuretic activity • Xanthines - theophylline, caffeine • osmotic diuretics - urea • carbonic-anhydrase inhibitors • thiazides • loop diuretics • aldosterone antagonists • potassium sparing diuretics

  7. How do they work? • Direct effect on cells of the nephron.. • where most of the active and selective solute reabsorption occurs • ascending loop of Henle • early distal tubule • collecting tubules and ducts • OR • modifying the content of the filtrate by their presence

  8. Loop diuretics (Rang and Dale p361-363) • Frusemide, bumetanide, piretanide • act on thick segment of ascending loop • inhibit NaCl transport OUT of tubule by inhibiting Na+/K+/2Cl- carrier (co-transporter) in luminal membrane ( acting on chloride binding site) • Reduces the hypertonic interstitial area in the medull, so reducing water re-absorption • increases Na+ solute concentration in the distal tubule which is exchanged for K+ andH+ (hypokalemia and alkalosis) • Can increase the excreted sodium from 1% to 15% of filtrate • Also reduce peripheral vascular resistance

  9. Loop diuretics • Kinetics • oral and IV preparations • bound to plasma protein, secreted into tubule • metabolised by the liver ( P450) • act within 1 hour • half life about 90 minutes; longer in renal failure • duration - 3-6 hours (Lasts Six Hours – Lasix)

  10. Loop diuretics • Effects • pass urine – in large amounts! • Side effects • electrolyte depletion • Hypovolemia • other reactions rare • Main Use • Heart failure – particularly acute left ventricular failure • Hepatic cirrhosis • Nephrotic syndrome • Renal failure

  11. thiazide diuretics • bendrofluazide, hydrochlorothiazide, indapamide • act on distal convoluted tubule • bind to chloride site of Na+/Cl co–transport system and inhibit action • decrease active Na resorption • decrease water resorption • changes in Ca, magnesium and uric acid

  12. thiazide diuretcis • kinetics • rapidly absorbed orally • secreted into the tubule • maximal effect 4- 6 hours, duration 8-12 hours

  13. thiazide diuretics • effects • increase urine output • side effects • electrolyte disturbances • increased cholesterol • impotence • hypersensitivity reactions (rare) • Main uses • hypertension • mild heart failure

  14. aldosterone antagonists • spirololactone • inhibits action of aldosterone (intracellular receptor binding anatagonism), increases sodium and decreases potassium secretion • kinetics • well absorbed orally, active metabolite half life of 16 hours • effects • limited diuresis • Main uses – heart failure and cirrhosis • side effects • Hyperkalemia, estrogen like effects

  15. other potassium sparing diuretics • Triamterene, amiloride • act on collecting ducts • inhibit Na resorption, decrease potassium excretion • effects • limited diuresis • side effects • electrolyte disturbances

  16. clinical choices • Uses: • cardiac failure • hypertension • fluid overload • NOT for everyone with oedema (eg from venous insufficiency) • acute versus chronic • evidence of benefit

  17. references • Rang & Dale, 5th edition • Cardiovascular Therapeutic Guidelines • Australian Medicines Handbook

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