Diuretics spironolactone

Amiloride (Midamor) is used in the treatment of CHF and hypertension and is often used with a thiazide diuretic. Spironolactone and triamterene are also used in tiie treatment of hypertension and edema caused by CHF, cirrhosis, and the nephrotic syndrome Amiloride, spironolactone, and triamterene are also available with hydrochlorothiazide, a thiazide diuretic that enhances tiie antihypertensive and diuretic effects of the drug combination while still conserving potassium. 

Hypertension therapy suggests wide use of diuretics, including thiazide diuretics, drugs related to them, such as metolazone (21.3.20) and indapamide (21.3.26), furosemide (21.4.11), loop diuretics, as well as potassium sparing diuretics—spironolactone (21.5.8), triamterene (21.5.13), and amyloride (21.5.18). 

Diuretics and their mechanisms of action will be discussed in detail in Chapter 21. Loop diuretics, such as furosemide (Lasix), block the Na" -K" -2CLsymporter in the ascending limb of the loop of Henle.The resultant effect is delivery of more Na" to the distal tubule and enhanced urinary loss of Na" and water. Unfortunately, the resultant increase in urinary excretion of and K+ can lead to arrhythmias. The potential for arrhythmias is exacerbated by the loss of Mg++ and Ca++ and an underlying vulnerability of the myocardium in CHF. However, loop diuretics are still part of the mainstay of therapy for CHF despite these potential problems and the absence of well-controlled multicenter clinical trials. The rationale for their use is so compelling that placebo-controlled studies appear unethical. Moreover, furosemide was accepted as the standard of care in all of the clinical trials that form the basis for recommended therapy for CHF. The use of the potassiumsparing diuretic spironolactone has been shown to improve survival and is discussed below. 

Renal plasma flow and glomerular filtration rate are usually unaffected, but free water clearance may increase. Because most sodium is reabsorbed in the proximal renal tubules, spironolactone is relatively ineffective when administered alone. Concomitant administration of a diuretic which blocks re-absorption of sodium proximal to the distal portion of the nephron (such as a thiazide or loop diuretic) is required for maximum diuretic effects. When administered with other diuretics, spironolactone produces an additive or synergistic diuretic response and decreases potassium excretion caused by the other diuretic [65],... 

In some cases, the simple modification of a drug structure can essentially modify the biological activity profile, whilst preserving some part of the original activity. Drospirenone (see Chapter 11-17), an orally active progestin contraceptive with antimineralcorticoid properties, is an example of an analogue-based drug discovery process that started from the diuretic spironolactone. 

DIGITOXIN DIURETICS -SPIRONOLACTONE Conflicting results from volunteer studies some showed t (up to one-third) in the half-life of digitoxin, others a 1 (up to one-fifth) Uncertain at present Watch for either digitoxin toxicity or a poor response, particularly for the first month after starting spironolactone... 

OESTROGENS 1. ANTICANCER AND IMMUNOMODULATING DRUGS - cidosporin, tacrolimus 2. CALCIUM CHANNEL BLOCKERS-nicardipine, nisoldipine, verapamil 3. DIURETICS-spironolactone Risk of gynaecomastia Inhibition of 2-hydroxylation or 17-oxidation of oestradiol in the liver, causing T oestradiol pool in the body Watch for gynaecomastia and warn patients... 

Clinically important, potentially hazardous interactions with ACE inhibitors, potassium-sparing diuretics, spironolactone, triamterene... 

There is a theoretical risk of hyperkalaemia with preparations containing potassium citrate. Such preparations should be avoided in patients taking potassium-sparing diuretics, spironolactone and angiotensin-converting enzyme inhibitors, and in patients with heart or kidney disease. 

Possibly ACE inhibitors or ARBs, diuretics, spironolactone Possibly ACE inhibitors or ARBs, spironolactone... 

Like other diuretics, spironolactone should be initiated at a low dose and increased to treat symptoms. Spironolactone may be initiated at doses of 12.5 to 25 mg/day. Spironolactone shonld be avoided in severe renal failnre. Hyperkalemia and gynecomastia are the most common side effects. Eplerenone is a viable alternative to... 

Medications Many medications can have an effect upon the formation of estrogens or activity of androgens in the body. The diuretic spironolactone is a good example as it has an anti-androgenic... 

As with other K+-sparing diuretics, spironolactone often is coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. Such combinations result in increased mobilization of edema fluid while causing lesser perturbations of K+ homeostasis. Spironolactone is particularly useful in the treatment of primary hyperaldosteronism (adrenal adenomas or bilateral adrenal hyperplasia) and of refractory edema associated with secondary aldosteronism (cardiac failure, hepatic cirrhosis, nephrotic syndrome, and severe ascites). Spironolactone is considered the diuretic of choice in patients with hepatic cirrhosis. Added to standard therapy, spironolactone substantially reduces morbidity and mortality and ventricular arrhythmias in patients with heart failure. 

Sulfonamide diuretics Hydrochlorodiiazide Chlorthalidone Loop diuretics Furosemide Ediacrynic acid Potassium-sparing diuretics Spironolactone (Aldactone) Triamterene Amiloride Uricosuric diuretics Tienihc acid... 

Pitassium-sparing diuretics work in eitlier of two ways. Triamterene (Dyrenium) and amiloride (Midamor) depress tlie reabsoqition of sodium in tlie kidney tubules, tlierefore increasing sodium and water excretion. Botli dni additionally depress tlie excretion of potassium and tlierefore are called potassium-sparing (or jxjtassium-saving) diuretics. Spironolactone (Aldactone), also a potassium-sparing diuretic, ant onizes the action of aldosterone Aldosterone, a hormone produced by the adrenal cortex, enhance tlie reabsoqition of sodium in tlie distal convoluted tubules of tlie kidney. Wlien tliis activity of aldosterone is blocked, sodium (but not potassium) and water are excreted. 

Potassium-sparing diuretics Spironolactone, amiloride Triamterene fi... 

Hypotension is more common in patients with heart failure who are receiving large doses of diuretics. In a study in 124 patients with severe heart failure, all receiving furosemide (mean dose 170 mg daily range 80 to 500 mg daily) and 90 also receiving the potassium-sparing diuretic spironolactone, the addition of captopril caused transient symptomatic hypotension in 44% of subjects. The captopril dose had to be reduced, and in 8 patients it was later discontinued. In addition, four patients developed symptomatic hypotension after 1 to 2 months of treatment, and captopril was also discontinued in these patients. ... 

The loop diuretics, bumetanide, furosemide and torasemide, the potassium-sparing diuretic spironolactone, and the thiazides chlortalidone and chlorothiazide, have all been shown either not to interact or to cause only a small reduction in the effects of the coumarin anticoagulants of minimal or no clinical importance. The lack of reports of clinically relevant interactions su ests that, in general, diuretics do not interact with anticoagulants. The possible exception is etacrynic acid, which on rare occasions has caused a marked increase in the effects of warfarin. 

On the other hand, the retention factor of the most retained diuretic, spironolactone, at a relatively large concentration of SDS (0.15 M), was too high (retention factor, k = 29). An organic modifier was required for lower retention. Methanol scarcely varied the retention of the diuretics and urine matrix. In contrast, 1-pentanol excessively reduced the retention and some diuretics were overlapped by the background of urine. 1-Propanol was found to be most appropriate because of its intermediate behavior. However,... 

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