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DIURETICS

DIURETICS. Prepared by Dr Rasol . M. Hasan. Background. Primary effect of diuretics is to increase solute excretion, mainly as NaCl Certain disease states may cause blood volume to increase outside of narrowly defined limits Hypertension Congestive heart failure Liver cirrhosis

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DIURETICS

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  1. DIURETICS Prepared by Dr Rasol . M. Hasan

  2. Background • Primary effect of diuretics is to increase solute excretion, mainly as NaCl • Certain disease states may cause blood volume to increase outside of narrowly defined limits • Hypertension • Congestive heart failure • Liver cirrhosis • Nephrotic syndrome • Renal failure • Dietary Na restriction often not enough to maintain ECF and to prevent edema  diuretics needed

  3. REVIEW OF KIDNEY STRUCTURE

  4. Principal parts of the kidney

  5. NEPHRON SITES OF ACTION OF DIURETICS

  6. The counter-current system

  7. TYPES OF DRUGS*Drugs that modify salt excretion1)Carbonic anhydrase inhibitors2)Loop diuretics3)Thiazide diuretics.4)K+ sparing diuretics.5)Osmotic diuretics.*Drugs that modify water excretion1)ADH agonists2)ADH antagonists.3)Osmotic diuretic.

  8. SITE OF DRUG ACTIONS CARBONIC ANHYDRASE INHIBITORS(work in proximal tubule) LOOP DIURETICS (ascending limb of loop) THIAZIDE DIURETICS (distal convolutedtubule) POTASSIUM-SPARING DIURETICS (collecting tubule) OSMOTIC (proximal tubule, descending loop of Henle, collecting duct)

  9. NEPHRON SITES OF ACTION OF DIURETICS

  10. Sites of diuretics • Proximal.c.tubule= 60-70% • Ascending loop Henle= 20-30% • Distal c. tubule = 5-8% • Cortical collecting ducts = 2-5%

  11. TYPES AND NAMES OF DIURETICS

  12. GENERAL BACKGROUND OF DIURETICS • Pattern of excretion of electrolytes (how much of which type) depends on class of diuretic agent • Maximal response is limited by site of action • Effect of two or more diuretics from different classes is additive or synergistic if there sites or mechanisms of action are different

  13. CARBONIC ANYDRASE INHIBITORS • Block carbonic-anhydrase in the cytoplam and brush borders. • C.anhyd.Inh plays an imp. role in the secretion of CSF and aqueous humor. • Major renal effect is BICARBONATE DIURESIS. • Useful for treating glaucoma and metabolic alkalosis. • CNS--acidosisHyperventilation->Protect against High altitude Sickness.

  14. LOOP DIURETICS • Generally cause greater diuresis than thiazides; used when they are insuffficient • Inhibit co-transport of Na+,K+ and Cl- AND excrete Ca+,and Mg+. • Short Acting (4 hours) • Efficacy of these durgs decreases with NSAIDS.and (e.g. probenecid).

  15. THIAZIDE DIURETICS • Active by Oral Route. • Inhibit NaCl transport in early segments of DCT. • Magnitude of effect is lower because work on distal convoluted tubule (only recieves 5-8% of filtrate) • Cause decreased Ca excretion  hypercalcemia  reduce osteoporosis

  16. POTASSIUM-SPARING DIURETICS • Have most downstream site of action (collecting tubule) • Reduce K loss by inhibiting Na/K exchange • Not a strong diuretic because action is furthest downstream • Often used in combination with thiazide diuretics to restrict K loss.

  17. OSMOTIC DIURETICS • No interaction with transport systems • All activity depends on osmotic pressure exerted in lumen • Blocks water reabsorption in proximal tubule, descending loop, collecting duct • Results in large water loss, smaller electrolyte loss  can result in hypernatremia,and hyperkalemia.

  18. ADH AGONISTS & ANTAGONISTS • AGONISTS facilitates reabsorption from the collecting tubules. • Reduces urine volume and increase its concentration • ANTAGONISTS oppose the action of ADH. • Can cause significant water retention & dangerous hyponatremia.

  19. THERAPEUTIC USES: CARBONIC ANHYDRASE INHIBITORS • Cystinuria (increase alkalinity of tubular urine) • Glaucoma (decrease ocular pressure) • Acute mountain sickness • Metabolic alkalosis LOOP DIURETICS • Hypertension, in patients with impaired renal function • Congestive heart failure (moderate to severe) • Acute pulmonary edema • Chronic or acute renal failure • Nephrotic syndrome • Hyperkalemia • Chemical intoxication (to increase urine flow)

  20. THIAZIDE DIURETICS • Hypertension • Congestive heart failure (mild) • Renal calculi • Nephrogenic diabetes insipidus • Chronic renal failure (as an adjunct to loop diuretic) • Osteoporosis

  21. POTASSIUM-SPARING DIURETICS • Chronic liver failure with ascites • Congestive heart failure, when hypokalemia is a problem OSMOTIC AGENTS • Reduce pre-surgical or post-trauma intracranial pressure • Prompt removal of renal toxins • Reduces intraocular pressure in Acute Glaucoma. ADH AGONISTS..Pituitary Diabetes Insipidus ANTAGONISTS…SIADH

  22. ADVERSE EFFECTS

  23. Thanks for your attention

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