Spironolactone side effects

Spironolactone antagonizes the effects of aldosterone by binding at the aldosterone receptor in the cytosol of the late distal tubules and renal collecting ducts. Side effects of spironolactone are gynecomastia, decreased Hbido, and impotency. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

Doses should be titrated at intervals no more frequent than every 2 to 3 days. Because spironolactone is used for its antialdosterone effects, much higher doses (up to 400 mg/day) are used than those used when treating hypertension. If intolerable side effects such as gynecomastia occur with spironolactone, other potassium-sparing diuretics may be used, but clinical trials have not shown equivalent efficacy.22... 

Spironolactone is poorly absorbed after oral administration and has a delayed onset of action it may take several days until a peak effect is produced. It has a somewhat slower onset of action than triamterene and amiloride (discussed later), but its natriuretic effect is modestly more pronounced, especially during long-term therapy. Spironolactone is rapidly and extensively metabolized, largely to the active metabohte canrenone. Canrenone and potassium canrenoate, its K+ salt, are available for clinical use in some countries outside the United States. Canrenone has a half-life of approximately 10 to 35 hours. The metabolites of spironolactone are excreted in both the urine and feces. New selective aldosterone receptor antagonists (SARA), such as eplerenone, have been developed but have not yet been introduced into clinical practice. Eplerenone and canrenone exhibit fewer steroidlike side effects (gynecomastia, hirsutism). 

Yemisci A, Gorgulu A, Piskin S. Effects and side-effects of spironolactone therapy in women with acne. J Eur Acad Dermatol Venereol 2005 19(2) 163-6. 

Spironothiazid is a diureteic and an ALDOSTERONE antagonist. This means that it suppresses the water retaining actions of the hormone ALDOSTERONE while lowering water retention by lowering electrolytes (potassium, sodium, and calcium). The advantage of the combination is that the potassium absorption effect by the spironolactone can be mediated by the hydrochlorthiazide. Because of this, some of the potassium loss side effects can be avoided. This is probably a safer choice than LASIX though any diuretic use should be medically monitored. Thiazides also lead to a lower loss of calcium. 

Potassium-sparing diuretics, such as amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium), impair the ability of the kidneys to filter potassium from the body. This can result in a condition called hyperkalemia, or excessive potassium, a potentially dangerous situation (see Harmful side effects section). Anyone taking potassium-sparing diuretics should avoid excessive dietary intake of foods high in the mineral. Bananas, tomatoes, sweet potatoes, and oranges are some of the foods that are rich in potassium. 

In animal tests, the biological profile of spirorenone achieved the proposed goal, with the compound displaying five-fold higher anti-aldosterone activity compared to spironolactone, but with far fewer hormonal side effects. This outcome was deemed highly successful, especially as since 1957 - the year in which spiro-... 

The aim is to remove the fluid gradually with a maximum weight loss of 0.5 kg/day in the absence of peripheral oedema, or 1.0 kg/day if peripheral oedema is present. Too rapid a diuresis will result in intravascular fluid loss rather than the peripheral oedema. The diuretic should be stopped if the serum sodium falls below 120 mmol/L or if there is a rising serum creatinine. Urinary electrolytes should be monitored to ensure that the spironolactone therapy is effective. The aim is to reverse the sodium/potassium ratio in the urine so that more sodium than potassium is excreted. Most frequent side-effects of spironolactone are those related to its anti-androgenic activity, such as decreased libido, impotence and gynaecomastia in men and menstrual irregularities in women. Other side-effects include hyperkalaemia, uraemia, hyponatraemia and nausea. 

Should these measures prove inadequate, either because of insufficient compliance on the part of the patient or because of the advanced stage of the disease, spironolactone (50 mg every second day) is recommended. This dose is considered effective and sufficient (due to its longer half-life). As a rule, there are no side effects. 

Step 1 (7.) lactulose (2-3 stools/day) and (2.) spironolactone (50 mg per day or every second day). This dosage is practically free of side effects - even during longterm administration, (s. pp 278, 306, 858)... 

Figure 18-14 Aldosterone enhances (he passage of tla from the luminal fluid into tubular cells and the passag o intracellular K into the luminal fluid at site 4 Progesteiir inhibits these actions of aldosterone but has undesirable 10--monal side effeas Spironolactone and canrenone also competitively inhibit (he actions of aldosterone at site 4 and are asset ated with a lower frequency of hormonal side effects.

In the past,. spironolactone has not enjoyed widespread UK for several well-documented reasons.First, its maximal effectiveness is usually not observed for 3 to S seeks. Second, its residual hormonal side effects have pro-J ja d unacceptable rates of gynecomastia in males and men-iimal irregularities in females, especially when doses exceeded 50 to 100 mg/day. These hormonal side effects can tv largely avoided by giving spironolactone in doses of 12.5 m25 mg/day. 

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... 

Spironolactone is available as 25-mg, 50-mg, and 100-mg tablets. The usual starting dose is 25 to 50 mg daily, and can be titrated to a maximum dose of 400 mg/day. The potassium-retaining effects generally take about 48 hours to occur. Important side effects... 

Interactions between Li and diuretics (especially spironolactone and amiloride) and nonsteroidal anti-inflammatory agents have been discussed above (see Absorption, Distribution, and Excretion and Toxic Reactions and Side Effects). Relative to thiazides and other diuretics that deplete Naf... 

Spironolactone (aldactone) ("see Chapter 28) is an aldosterone antagonist that also is a weakAR antagonist and a weak inhibitor of testosterone synthesis, apparently inhibiting CYP17. When used to treat fluid retention or hypertension in men, gynecomastia is a common side effect. 

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