DIURETICS

¢Drugs causing net loss of Na+  and water in urine.

¢Causes increase in urine volume due to increased osmotic pressure in lumen of renal tubule.

¢Causes concomitant decrease in extra-cellular volume (blood volume)

¢Carbonic anhydrase inhibitors

¢Loop diuretics

¢Osmotic diuretics

¢Potassium-sparing diuretics

¢Thiazide and thiazide-like diuretics

¢Acetazolamide

¢Methazolamide

¢Dichlorphenamide

¢The enzyme carbonic anhydrase helps to make H+ ions available for exchange with sodium and water in the proximal tubules

¢MOA:

—block the action of carbonic anhydrase,

—thus preventing the exchange of H+ ions with sodium and water

—reduces H+ ion concentration in renal tubules

¢Result:

—increased excretion of  bicarbonate, sodium, water, & K+

—Resorption of water is decreased and urine volume is increased

¢Clinical uses:

¢Adjunct used with miotics in the long-term management of glaucoma.

¢Edema

¢Epilepsy

¢High-altitude sickness

¢Metabolic alkalosis but can cause hyperchloremic metabolic acidosis from HCO3- depletion.

¢Acetazolamide is used in the management of edema secondary to heart failure when other diuretics are not effective.

¢CAIs are less potent diuretics than loop diuretics or thiazides—the metabolic acidosis they induce reduces their diuretic effect in 2-4 days

 Adverse Effects:

¢Metabolic acidosis

¢Anorexia

¢Hematuria 

¢Melena

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¢Hypokalemia

¢Drowsiness

¢Paresthesia

¢Urticaria

¢Generally cause greater diuresis than thiazides; used when they are insufficient.

¢Can enhance Ca2+ and Mg2+ excretion

¢Enter tubular lumen via proximal tubular secretion.

¢Drugs that block this secretion (e.g. probenecid) reduces efficacy

¢Bumetanide

¢Ethacrynic acid

¢Furosemide

¢Ascending loop contains Na+ - K+ - 2Cl- cotransporter from lumen to ascending limb cells

¢Loop diuretic blocks cotransporter à Na+, K+, and Cl- remain in lumen, excreted along with water.

¢Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance

¢Potent diuresis and subsequent loss of fluid

¢Decreased fluid volume causes:

—Reduced BP

—Reduced pulmonary vascular resistance

—Reduced systemic vascular resistance

—Reduced central venous pressure

—Reduced left ventricular end-diastolic pressure

¢Potassium and sodium depletion

¢Clinical uses:

¢Edema associated with heart failure or hepatic
or renal disease

¢Control of hypertension

¢Increase renal excretion of calcium in patients with hypercalcemia

Ototoxicity

CNS: Dizziness, headache, tinnitus, blurred vision

Metabolic:Hypokalemia, Hyponatrimia

Dehydration

GI: Nausea, vomiting, diarrhea