Diuretics PDF

Diuretics Diuretics are ion transport inhibitors that decrease the reabsorption of sodium at various sites in the nephron.  Diuretic drugs reduce the reabsorption of sodium in renal tubules and thus increase the excretion of water in the urine  furosemide (Lasix) is a loop diu...

Diuretics Diuretics are ion transport inhibitors that decrease the reabsorption of sodium at various sites in the nephron.  Diuretic drugs reduce the reabsorption of sodium in renal tubules and thus increase the excretion of water in the urine  furosemide (Lasix) is a loop diuretic - acting in the ascending loop of Henle  hydrochlorothiazide (HCTZ) is a thiazide diuretic - it acts in the distal convoluted tubule.  triamterene (Dyrenium) is a potassium sparing diuretic - it acts on the late distal tubule and collecting duct Loop Diuretics Drugs in this class:  Furosemide (Lasix) prototype  Ethacrynic (Edecrin)  Bumetanide (Bumex)  Torsemide (Demadex) Mechanism of Action  Loop diuretics act in the ascending limb of the Loop of Henle to inhibit sodium and chloride reabsorption. They bind to and inhibit a transporter protein. They are the most powerful of the diuretics because the ascending limb accounts for most of the sodium filtering. They are sometimes referred to as “high ceiling” diuretics. Other diuretic classes are compared to the loop diuretics in their ability to produce a diuresis.  Loop diuretics also have an indirect vasodilator action secondary to the release of prostaglandin E2 by inhibiting the enzyme prostaglandin dehydrogenase. This action leads to a decreased in preload and helps relieve pulmonary edema when the drug is given intravenously. The prostaglandin E2 also acts directly on the ascending limb to inhibit chloride transport resulting in improved hemodynamics even before significant diuresis has occurred. Adverse Effects: Most adverse effects and contraindications to the use of loop diuretics are related to fluid and electrolyte imbalance. When the loop diuretics cause increases in sodium excretion, potassium, hydrogen, calcium and magnesium ions follow. The common adverse effects are related to a decrease in these ions. Hypokalemia: potassium is lost along with the water so you should monitor potassium levels and supplement with potassium chloride if the patient is hypokalemic. Additional risk if patient is taking digoxin as hypokalemia potentiates digoxin toxicity. Hypomagnesemia Metabolic alkalosis Hypocalcemia Hypovolemia and hypotension due to volume contraction and loss of electrolytes Ototoxicity if given rapid IVP due to alteration in electrolytes in the inner ear Hyperuricemia Allergic reaction: furosemide, bumetanide and torsemide all have a structure similar to the sulfonamide antibiotics and you can see cross-reactivity in patients that are allergic to the sulfonamides. This cross-reactivity is uncommon but you should use caution, especially in patients who have had serious allergic reactions to sulfa antibiotics. Clinical Use of Loop Diuretics  Used in the management of edema related to heart failure, renal disease, and hepatic cirrhosis  Very effective in treating pulmonary edema as loop diuretics can increase pulmonary lymphatic drainage  Effective in treating moderate to severe CHF  Oral absorption may be decreased by 40% in acute CHF  Extent of diuresis is the same with IV and oral, although the onset of diuresis is more rapid with IV administration. Thiazide and Thiazide-like Diuretics Drugs in this class:  Chlorothiazide (Diuril)  Chlorthalidone (Hygroton)  Hydrochlorothiazide (HCTZ)  Indapamide (Lozol)  Metolazone (Zaroxolyn) Mechanism of Action: Thiazide diuretics inhibit the sodium and chloride transporter at the distal convoluted tubule in the nephron. This decreases the reabsorption of sodium at the distal tubule, thus increasing sodium and water excretion into the urine. The thiazides produce less diuresis because by the time the filtrates have reached the distal tubules, 90% of the sodium originally filtered at the glomerulus has already been reabsorbed. Adverse Effects:  hypokalemia  hypomagnesemia  hypercalcemia  hyperglycemia  hyperuricemia  hyperlipidemia Clinical Use of Thiazide Diuretics:  Diuretic of choice in treatment of primary hypertension important to know  Usually only effective in mild CHF  Not effective in patients with eGFR < 30-40 ml/min except metolazone, which may be effective at large doses in renal impairment. If eGFR is less than 40ml/min use furosemide instead also important to know  Use with caution in patients with severe renal and liver impairment, and in patients with a history of hypersensitivity to other sulfonamide derivatives. Potassium Sparing Diuretics Drugs in this class:  Amiloride (Midamor)  Spironolactone (Aldactone)  Triamterene (Dyrenium) Mechanism of action:  Spironolactone blocks the action of aldosterone, and endogenous mineralcorticoid. Aldosterone causes a decrease in sodium excretion and an increase in potassium and hydrogen excretion. Spironolactone antagonizes these effects.  Triamterene and amiloride block sodium channels in the late distal tubule and collecting duct of the nephron. By blocking this channel, there is decreased intracellular sodium concentrations that leads to decreased sodium/potassium ATPase activity and there is less sodium reabsorption and less potassium excretion.  Both types of potassium sparing diuretics are weak diuretics and are used clinically more for their potassium-sparing properties and used in conjunction with another diuretic. Adverse Effects:  Hyperkalemia - especially in conjunction with potassium supplementation or with ACE inhibitors  Gynecomastia, impotence - seen with high dose spironolactone due to the blocking of steroid receptor sites Clinical Use of Potassium Sparing Diuretics  All are weak diuretics when used as diuretic monotherapy  Their ability to protect against potassium loss makes them beneficial as adjunct therapy with other diuretics  It has long been known that patients with CHF have increased levels of aldosterone. ACE inhibitors reduce the levels of Angiotensin II and decrease aldosterone levels as well, but, it is also known that there is a phenomenon called "aldosterone escape" where aldosterone levels increase again even if ACE inhibitor therapy is continued. Studies have shown that adding a small dose of spironolactone to the drug regimen of patients with heart failure will decrease morbidity and mortality. Selective Aldosterone Receptor Antagonists Drugs in this class:  Eplerenone (Inspra) Mechanism of action  Aldosterone inhibitor  Binds to the mineralocorticoid receptor in both epithelial (e.g. kidney) and nonepithelial (e.g. heart blood vessels, brain) tissues and blocks the binding of aldosterone at the receptors.  Similar activity as spironolactone in heart failure, but more selective for the aldosterone receptor, so fewer side effects Adverse Effects  hyperkalemia Clinical Use  Eplerenone improves survival of stable patients with left ventricular systolic dysfunction and clinical evidence of heart failure following an acute MI  Drug interactions include drugs that inhibit CYP 3A4 enzyme including several antibiotics (e.g erythromycin) and antifungal (e.g ketoconazole) and antiviral drugs (e.g. saquinavir).  Grapefruit juice increases absorption of eplerenone.  2005 ACC/AHA CHF guidelines recommend adding spironolactone or eplerenone to the drug regimen of patients with moderate-severe symptoms of heart failure with careful monitoring of renal function and serum potassium. Serum creatinine should be