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DIURETICS

DIURETICS. Prof. Hanan Hagar Pharmacology Department. Classification of diuretics. Carbonic Anhydrase Inhibitors Loop Diuretics Thiazides Potassium-Sparing Diuretics Osmotic Diuretics. SITES OF ACTION OF DIURETICS. Thiazide diuretics. Mechanism of action:

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DIURETICS

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  1. DIURETICS Prof. Hanan Hagar Pharmacology Department

  2. Classification of diuretics • Carbonic Anhydrase Inhibitors • Loop Diuretics • Thiazides • Potassium-Sparing Diuretics • Osmotic Diuretics

  3. SITES OF ACTION OF DIURETICS

  4. Thiazide diuretics Mechanism of action: • acts via inhibition of Na/Cl co-transporter on the luminal membrane of distal convoluted tubules • Efficacy: Moderate 5% natriuresis • Drugs as: • chlorothiazide-hydrochlorothiazide • Metolazone

  5. Distal convoluted tubules

  6. Mechanism of action of thiazide diuretics

  7. Pharmacokinetics: • Given orally, slow of onset • long duration of action (40 h) • are secreted by active tubular secretory system of the kidney • may interfere with uric acid secretion and cause hyperuricemia

  8. Pharmacological effects: urinary NaCl excretion urinary K excretion (Hypokalemia) urinary magnesium excretion urinary calcium excretion calcium re-absorption hypercalcemia

  9. Thiazide diuretics

  10. Uses: • Treatment of essential hypertension (cheap-well tolerated) • Treatment of mild heart failure (to reduce extracellular volume).

  11. Uses: • Nephrolithiasis due to hypercalciuria(to increase calcium re-absorption and decrease renal calcium stones) • Nephrogenic diabetes insipidus (decrease blood volume and GFR)

  12. Adverse effects: • Fluid and electrolyte imbalance • Hyponatremia • Hypovolemia (volume depletion) • Hypokalemia • Metabolic alkalosis. • Hyperuricaemia (gout) • Hypercalcemia • Hyperglycaemia • Hyperlipidemia

  13. Potassium sparing diuretics Drugs: • Spironolactone. • Triamterene. • Amiloride. • given by oral administration

  14. Mechanism of action • Act in collecting tubules and ducts by inhibiting Na re-absorption and K & H secretion (K-sparing effect) by either: • Inhibition of Na influx through Na channels in the luminal membrane (triamterene – amiloride).

  15. Mechanism of action • Or by antagonizing cytoplasmic aldosterone receptors (mineralocorticoid receptors Spironolactone). • Spironolactone : is a synthetic steroid that acts as a competitive antagonist for aldosterone.

  16. Collected tubules (CT)

  17. Pharmacodynamics: • urinary Na excretion • urinary K excretion hyperkalemia • H secretion (acidosis)

  18. Therapeutic uses: • Drug of choice for patients with hepatic cirrhosis • In mineralocorticoid hypersecretion e.g. Conn’s syndrome

  19. Therapeutic uses: • Secondary hyperaldosteronism: (CHF, hepatic cirrhosis, nephrotic syndrome). • Treatment of hypertension (combined with thiazide or loop diuretics to correct for hypokalemia).

  20. Adverse Effects • Hyperkalaemia. • Metabolic acidosis. • Gynaecomastia • GIT upset and peptic ulcer

  21. Contraindications: • Hyperkalaemia: as in chronic renal failure, K+ supplementation, -blockers or ACE inhibitors. • liver disease (dose adjustment is needed).

  22. Osmotic diuretics Mannitol • Poorly absorbed • Given intravenously. • Not metabolized • Excreted by glomerular filtration without being re-absorbed or secreted within 30-60 min.

  23. Mannitol • Acts in proximal tubules & descending loop of Henle by osmotic effect. • Retains water within the tubules (water diuresis). • Has a secondary effect on reducing sodium re-absorption.

  24. Therapeutic Uses: • Cerebral edema (increased intracranial pressure). • Glaucoma. • Acute renal failure due to shock, trauma, drug toxicities (maintain urine flow- preserve kidney function).

  25. Adverse Effects: • Extracellular water expansion (extracts water from cells) • Dehydration • Hypernatremia • Headache, nausea, vomiting • Adequate water replacement is required.

  26. Therapeutic applications of diuretics Treatment of hypertension: • Thiazide diuretics • used alone or in combination with beta-blockers at low-dose (fewer side effects) • In presence of renal failure, loop diuretic is used. Edema States Thiazide diuretic is used in mild edema with normal renal function • Loop diuretics are used in cases with impaired renal function.

  27. Congestive Heart failure • Thiazides may be used in only mild cases with well-preserved renal function • Loop diuretics are much preferred in severe cases especially when GF is lowered • In life-threatening acute pulmonary edema, furosemide is given IV.

  28. Renal failure • Thiazides are used till GFR ≥ 40-50 ml/min • Loop diuretic are used below given values, with increasing the dose with as GFR goes down. Diabetes inspidus Large volume(>10 L/day) of dilute urine thiazide diuretics reduces urine volume Hepatic cirrhosis with ascites • Spironolactone is of choice.

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