387, thiazide diuretics congestive heart failure

Therapy of congestive heart failure. By lowering peripheral resistance, diuretics aid the heart in ejecting blood (reduction in afterload, pp. 132, 306) cardiac output and exercise tolerance are increased. Due to the increased excretion of fluid, EEV and venous return decrease (reduction in preload, p. 306). Symptoms of venous congestion, such as ankle edema and hepatic enlargement, subside. The drugs principally used are thiazides (possibly combined with K+-sparing diuretics) and loop diuretics. 

Captopril, as well as other ACE inhibitors, is indicated in the treatment of hypertension, congestive heart failure, left ventricular dysfunction after a myocardial infarction, and diabetic nephropathy. In the treatment of essential hypertension, captopril is considered first-choice therapy, either alone or in combination with a thiazide diuretic. Decreases in blood pressure are primarily attributed to decreased total peripheral resistance or afterload. An advantage of combining captopril therapy with a conventional thiazide diuretic is that the thiazide-induced hypokalemia is minimized in the presence of ACE inhibition, since there is a marked decrease in angiotensin Il-induced aldosterone release. 

Triamterene can be used in the treatment of congestive heart failure, cirrhosis, and the edema caused by secondary hyperaldosteronism. It is frequently used in combination with other diuretics except spironolactone. Amiloride, but not triamterene, possesses antihypertensive effects that can add to those of the thiazides. 

Potassium-sparing diuretics include amiloride (Midamor) and triamterene (Dyrenium). They are used in the treatment of cirrhosis and congestive heart failure. They may be used in conjunction with thiazide diuretics to offset the potassium loss associated with those medications. 

Adverse effects Thiazide diuretics induce hypokalemia and hyperuricemia in 70% of patients, and hyperglycemia in 10% of patients. Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias (particularly individuals with left ventricular hypertrophy, ischemic heart disease, or chronic congestive heart failure) and who are concurrently being treated with both thiazide diuretics and digitalis glycosides (see p. 160). Diuretics should be avoided in the treatment of hypertensive diabetics or patients with hyperlipidemia. 

Chlorothiazide [klor oh THYE a zide], the prototype thiazide diuretic, was the first modern diuretic that was active orally and was capable of affecting the severe edema of cirrhosis and congestive heart failure with a minimum of side effects. Its properties are representative of the thiazide group, although newer derivatives such as hydrochlorothiazide or chlorthalidone are now used more commonly. 

Q9 What is the mechanism of action of loop diuretics and why may they be more useful in congestive heart failure than the thiazides ... 

Diuretics are highly efficient drugs for the treatment of edema associated with congestive heart failure. They are also used to increase the volume of urine excreted by the kidneys [9]. For example, duranide, 81, a dichlorinated benzene disulfonamide, is an oral carbonic anhydrase inhibitor. Duranide reduces intraocular pressure by partially suppressing the secretion of aqueous humor [11]. Diuril, 82, has an antihypertensive activity and is issued to control blood pressure [9]. Edecrin, 83, is an unsaturated ketone derivative of an aryloxyacetic acid. Edecrin is used in the treatment of the edema associated with congestive heart failure, renal disease, and cirrhosis of the liver [11]. Amiloride, 84, is also used as an adjunctive treatment with thiazide diuretics in congestive heart failure hypertension. 

Amiloride interferes with sodium reabsorption at the distal tubule, resulting in increased excretion of water and sodium and decreased excretion of potassium. It is indicated in the treatment of congestive heart failure or hypertension (in combination with thiazide or loop diuretics) and diuretic-induced hypokalemia. 

Amiloride is used with thiazide or loop diuretics in hypertension, in congestive heart failure, in digitalis-induced hypokalemia, and in arrhythmias resulting from hypokalemia. Inappropriate use of amiloride may cause hyperkalemia (potassium >5.5 mEq/L), which may be fatal if not corrected, and may be more deleterious in elderly individuals and in patients with diabetes mellitus and renal impairment. The symptoms of hyperkalemia include fatigue, flaccid paralysis of the extremities, paresthesias, bradycardia, ECG abnormalities, and shock. Amiloride is not metabolized but is contraindicated in anuria, acute or chronic renal insufficiency, or in diabetic nephropathy. It should not be used with potassium preparations, and should be used cautiously with ACE inhibitors because these agents cause hyperkalemia. 

THERAPEUTIC USES Thiazide diuretics are used to treat edema associated with heart (congestive heart failure), liver (cirrhosis), and renal (nephrotic syndrome, chronic renal failure, and acute glomerulonephritis) disease. With the possible exceptions of metolazone and indapamide, most thiazide diuretics are ineffective when the GFR is <30-40 mL/min. 

Spironolactone is an antagonist to aldosterone —the latter when elaborated in the body in excessive amounts gives rise to a syndrome called aldosteronism. Spironolactone, a synthetically produced steroid does not have a natural counterpart in the body, is diuretic when mercurial or thiazide diuretics are ineffective it prevents sodium retention and potassium excretion— effects opposite to aldosterone. Hence spironolactone is used in aldosteronism, against edema, in the treatment of congestive heart failure and in other conditions in which an accumulation of water, and water-retaining salt, is to be corrected. 

A. Diuretics Diuretics are often used in congestive heart failure before digitalis and other drugs are considered. Furosemide is a very useful agent for immediate reduction of the pulmonary congestion and severe edema associated with acute congestive heart failure or severe chronic failure. Thiazides such as hydrochlorothiazide are often used in the management of mild... 

It is a quinazoline-derived nonthiazide diuretic. It is found to be more effective in comparison to the thiazide-like diuretics in the treatment of edema in such patients who have a histoiy of compromised renal function. It is extensively indicated for hypertension, edema accompanying congestive heart failure, renal disease including the nephrotic syndrome and other conditions of retarded renal function. 

Triamterene is usually recommended in the treatment of oedema associated with nephrotic syndrome, cirrhosis of liver, and congestive heart failure. It has also been used for the control and management of idiopathic oedema, steroid-induced oedema, oedema caused by hyperaldosteronism and in such oedematus patients who fail to respond to other therapy. It is usually used in conjunction with other diuretics like thiazides. 

It is employed in the treatment of refraetory oedema assoeiated with congestive heart-failure, cirrhosis of the liver or the nephrotic syndrome. It is frequently administered along with diuretics like thiazides and frusemide whereby it adds to their natriuretic but retards thir kaliuretie effects, hence conserving potassium. 

Uses of indapamide inciude the treatment of essentiai hypertension and edema resulting from congestive heart failure. Like metolazone. indapamide is an effective diuretic drug when GFR faiis beiow 40 mL/min. The duration of action is approximately 24 hours, with the normal oral adult dosage starting at 2.5 mg given each morning. The dose may be increased to 5.0 mg/day, but doses beyond this ievei do not appear to provide additional results. Effects on urine content and side effects are similar to effects induced by thiazide diuretics. 

---