Heart failure, chronic diuretics

Congestive heart failure/chronic renal failure - The usual initial dose is 10 or 20 mg once daily oral or IV. If the diuretic response is inadequate, titrate the dose upward by approximately doubling until the desired diuretic response is... 

The drugs most commonly used in chronic heart failure are diuretics, ACE inhibitors, angiotensin receptor antagonists, and U-blockers (Table 13-1). In acute failure, diuretics and vasodilators play important roles. 

Medications can increase the risk of hyperkalemia in patients with CKD, including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, used for the treatment of proteinuria and hypertension. Potassium-sparing diuretics, used for the treatment of edema and chronic heart failure, can also exacerbate the development of hyperkalemia, and should be used with caution in patients with stage 3 CKD or higher. 

Nephron adaptation to chronic diuretic therapy NSAID use Heart failure... 

Cardiovascular effects May cause fluid retention and peripheral edema. Use caution in compromised cardiac function, hypertension, in patients on chronic diuretic therapy, or other conditions predisposing to fluid retention. Agents may be associated with significant deterioration of circulatory hemodynamics in severe heart failure and hyponatremia. 

The chronic use of some diuretics may require the oral administration of potassium supplements or potassiumsparing diuretics that reduce urinary K+ excretion. This is true especially for patients with congestive heart failure and cirrhosis, who are particularly sensitive to K+ loss. The presence or absence of clinical symptoms of hypokalemia is quite closely related to serum K+ concentrations, and even small changes in extracellular K+ can have marked effects. Most patients begin to show symptoms when serum K+ levels fall below 2.5 mEq/L (from a normal value of approximately 5 mEq/L). 

In patients with left ventricular dysfunction but no edema, an ACE inhibitor should be used first. Several large studies have showed clearly that ACE inhibitors are superior to both placebo and to vasodilators and must be considered, along with diuretics, as first-line therapy for chronic heart failure. However, ACE inhibitors cannot replace digoxin in patients already receiving the drug because patients withdrawn from the cardiac glycoside deteriorate while on ACE inhibitor therapy. 

Furosemide Loop diuretic Decreases NaCI and KCI reabsorption in thick ascending limb of the loop of Henle in the nephron (see Chapter 15) Increased excretion of salt and water reduces cardiac preload and afterload reduces pulmonary and peripheral edema Acute and chronic heart failure severe hypertension edematous conditions Oral and IV duration 2-4 h Toxicity Hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, sulfonamide allergy... 

Researchers John Baer, Karl Beyer (1914—1996), James Sprague (1916- ), and Frederick Novello formulate the drug chlorothiazide, the first of the thiazide diuretics. This groundbreaking discovery marked a new era in medicine as the first safe and effective long-term treatment for chronic hypertension and heart failure. 

In the past, prescription of a diuretic plus digitalis was almost automatic in every case of chronic heart failure, and other drugs were rarely considered. At present, diuretics are still considered as first-line therapy, but digitalis is usually reserved for patients who do not respond adequately to diuretics, ACE inhibitors, and B-blockers (Table 13-1). 

Examples of specific drugs used in the treatment of chronic heart failure include digitalis glycosides (e.g., digoxin, positive inotropic agent), diuretics (hydrochlortiazide and furosemide), and vasodilators (nitrates such as nitroglycerin, ACE inhibitors, such as captopril, and hydralazine). 

Chronic heart failure is typically managed by reduction in physical activity, low dietary intake of sodium (less than 1500 mg sodium per day), and treatment with vasodilators, diuretics and inotropic agents. Drugs that may precipitate or exacerbate CHF—nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, (3-blockers, calcium channel-blockers and some antiarrhythmic drugs—should be avoided if possible. Patients with CHF complain of dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and dependent edema. 

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. 

Like p-blockers, ACE inhibitors are most effective in hypertensive patients who are white and young. However, when used in combination with a diuretic, the effectiveness of ACE inhibitors is similar in white and black hypertensive patients. Unlike p-blockers, ACE inhibitors are effective in the management of patients with chronic congestive heart failure (see p. 156). ACE inhibitors are now a standard in the care of a patient following a myocardial infarction. Therapy is started 24 hours after the end of the infarction. 

Beta-adrenoceptor blockers. The realisation that the coiuse of chronic heart failure can be adversely affected by activation of the renin-angiotensin-aldosterone and sympathetic nervous systems led to exploration of possible benefit from P-adrenoceptors in a condition where, paradoxically, such drugs can have an adverse effect. Clinical trials have, indeed, shown that bisoprolol, carvedilol or metoprolol lower mortality and decrease hospitalisation when added to diuretics, digoxin and an ACE inhibitor (see below). 

Furosemide is a widely used loop diuretic indicated for the treatment of different pathological conditions such as congestive heart failure, hepatic cirrhosis, and chronic renal failure. It has a narrow absorption window and mainly absorbed from the stomach and the upper part of the small intestine. Following administration of furosemide, the natriuretic effect rapidly disperses and is concealed before the next administration. This problematic aspect in furosemide therapy is mostly attributed to the natural homeostatic compensatory mechanisms. Lately, it has been demonstrated that the diuretic and natriuretic effects of furosemide can be significantly improved, following a continuous input (intravenous infusion) compared to immediate release DFs. Beside the narrow absorption window, this pharmacodynamic feature of the drug provides another rationale for the development of a GRDF for furosemide. 

Felodipine is a dihydropyridine derivative with diuretic properties (1). Its diuretic properties are not unique but are shared by other dihydropyridines. Its vasodilator-related adverse effects include flushing, headache, and tachycardia (2,3). Reduced arterial oxygen saturation has been seen in patients given intravenous felodipine for pulmonary hypertension (4,5). Along with amlodipine, but unlike other calcium channel blockers, felodipine may be safer in severe chronic heart failure accompanied by angina or hypertension. 

When it is used in cardiac failure, furosemide acts in two ways besides its diuretic effect it produces an immediate fall in left ventricular filhng pressure, which is independent of and precedes diuresis. If furosemide is given intravenously in stable chronic heart failure (which it normally is not), this can be an unwanted effect, causing deterioration (SEDA-11, 199), particularly in patients with pure right ventricular failure. 

Grinstead WC, Francis MJ, Marks GF, Tawa CB, Zoghbi WA, Young JB. Discontinuation of chronic diuretic therapy in stable congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy. Am J Cardiol 1994 73(12) 881-6. 

A series of 11 spontaneously reported cases in which renal impairment was associated with the use of nimesulide has been described (17). The adverse events were represented by acute renal insufficiency n — 2), acute deterioration of chronic renal insufficiency n — 3), fluid retention n = 4), and oliguria and macro hematuria n = 1 each). The patients had a median age of 57 (range 17-81) years and six had some predisposing condition (chronic renal insufficiency, heart failure, diabetes, use of diuretics) to NSAID-induced functional renal impairment. Apart from one patient, nimesulide was taken for a very short time (less than 8 days). A favorable outcome ensued after withdrawal of therapy in aU patients. The acute deterioration of renal function described in these patients pointed to hemodynamically mediated renal impairment in all cases, with the exception of one man in whom interstitial nephritis was suspected. 

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