Chapter 51 Diuretic Agents Classes of Diuretics Thiazide

Chapter 51 Diuretic Agents

Classes of Diuretics • Thiazide and thiazide-like diuretics • Loop diuretics • Carbonic anhydrase inhibitors • Potassium-sparing diuretics • Osmotic diuretics

Function of Diuretic Agents • Increase the amount of urine produced by the kidneys • Increase sodium excretion

Indications for Diuretic Use • Edema associated with congestive heart failure • Acute pulmonary edema • Liver disease (including cirrhosis) • Renal disease • Hypertension • Conditions that cause hyperkalemia

Causes of Edema and Ascites in Patients With Liver Failure • Reduced plasma protein production – Results in less oncotic pull in the vascular system and fluid loss at the capillary level • Obstructed blood flow through the portal system – Caused by increased pressure from congested hepatic vessels

Thiazide and Thiazide-Like Diuretics • Hydrochlorothiazide (Hydro. DIURIL) • Chlorothiazide (Diuril) • Bendroflumethiazide (Naturetin) • Benzthiazide (Exna) • Hydroflumethiazide (Diucardin) • Methyclothiazide (Aquatensen) • Polythiazide (Renese) • Trichlormethiazide (Diurese)

Sites of Action of Diuretics in the Nephron

Indications for Thiazide and Thiazide-Like Diuretics • Treatment of edema associated with CHF, liver, or renal disease • Monotherapy or adjuncts for the treatment of hypertension

Focus on the Prototype Thiazide Diuretic: Hydrochlorothiazide • Indications: Adjunctive therapy for edema associated with CHG, cirrhosis, corticosteroid and estrogen therapy, and renal dysfunction; treatment of hypertension • Actions: Inhibits reabsorption of sodium and chloride in distal renal tubules, increasing the excretion of sodium, chloride, and water by the kidneys • Oral route: Onset 2 h; peak 4– 6 h; duration 6– 12 h • T½: 5. 6– 14 h; metabolized in the liver and excreted in urine

Loop Diuretics Currently Available • Furosemide (Lasix) – Most commonly used; less powerful than new drugs; larger margin of safety for home use • Bumetanide (Bumex) and torsemide (Demadex) – New drugs; more powerful than Lasix • Ethacrynic acid (Edecrin) – First loop diuretic introduced, used less frequently in the clinical setting

Indications for Loop Diuretics • Acute CHF • Acute pulmonary edema • Edema associated with CHF • Edema associated with renal or liver disease • Hypertension

Focus on the Loop Diuretic Prototype: Furosemide • Indications: Treatment of edema associated with CHF, acute pulmonary edema, hypertension • Actions: Inhibits reabsorption of sodium and chloride from the proximal and distal renal tubules and the loop of Henle, leading to a sodium-rich diuresis • Oral route: Onset 60 min; peak 60– 120 min; duration 6 – 8 h • IV, IM route: Onset 5 min; peak 30 min; duration 2 h • T½: 120 min; metabolized in the liver and excreted in urine

Focus on the Carbonic Anhydrase Inhibitors Prototype: Acetazolamide (Diamox) • Indications: Treatment of glaucoma; edema caused by CHF, drug-induced edema; centrencephalic epilepsy; prophylaxis and treatment of acute altitude sickness • Actions: Inhibits carbonic anhydrase, which decreases aqueous humor formation in the eye; intraocular pressure and hydrogen secretion by the renal tubules • Routes: Oral, SR, IV • T½: 5– 6 hr; excreted unchanged in urine

Potassium-Sparing Diuretics • Types – Amiloride (Midamor) – Spironolactone (Aldactone) – Triamterene (Dyrenium) • Uses – Patients at high risk for hypokalemia associated with diuretic use

Osmotic Diuretics • Types – Glycerin (Osmoglyn), Isosorbide (Ismotic), Mannitol (Osmitrol), and Urea (Ureaphil) • Action – Pull water into the renal tubule without sodium loss • Indications – Increased cranial pressure or acute renal failure due to shock, drug overdose, or trauma