Spironolactone (Aldactone) is structurally similar to aldosterone and competitively inhibits its action in the distal tubule (exchange of potassium for sodium); excessive secretion of aldosterone contributes to fluid retention in hepatic cirrhosis, nephrotic syndrome and congestive cardiac failure (see specific use in chapter 24), in which conditions as well as in primary hypersecretion (Conn's syndrome) spironolactone is most useful. Spironolactone is also useful in the treatment of resistant hypertension, where increased aldosterone sensitivity is increasingly recognised as a contributory factor.
Spironolactone is extensively metabolised and the t\ is 8h. The most significant product, can-renone, is available as a drug in its own right, potassium canrenoate. The prolonged diuretic effect of spironolactone is explained by 17 h t1^ of can-renone. Spironolactone is relatively ineffective when used alone but may usefully be combined with a drug that reduces sodium reabsorption proximally in the tubule, e.g. a loop diuretic. Spironolactone (and amiloride and triamterene, see below) also reduces the potassium loss that occurs with loop diuretics, but use in combination with another potassium-sparing diuretic leads to hyperkalaemia. Dangerous potassium retention may also develop if spironolactone is given to patients with impaired renal function. It is given orally in one or more doses totalling 100-200 mg. Maximum diuresis is delayed for up to 4 days. If after 5 days response is inadequate, dose may be increased to 300-400 mg/d. 0.5-1 mg/kg are required in treating hypertension.
The oestrogenic side effects of spironolactone are the major limitation to its long-term use. They are dose-dependent, but in the RALES trial3 (see Chapter 24) even 25 mg/d caused breast tenderness or enlargement in 10% of men. Women may also report breast discomfort or menstrual irregularities including amenorrhoea. Minor gastrointestinal upset also occurs. These effects are reversible on stopping the drug. Possible human metabolites are carcinogenic in rodents; it seems unlikely after many years of clinical experience that the drug is carcinogenic in humans. In the UK, spironolactone is no longer licenced for use in essential hypertension, but retains its licence for other indications.
Amiloride exerts an inhibitory action on sodium channels under the influence of aldosterone in the distal tubule. Its action is therefore complementary to that of the thiazides and, used with them, it augments sodium loss and but limits potassium loss. One such combination, co-amilozide, (Moduretic) (amiloride 2.5-5 mg plus hydrochlorothiazide 2550 mg), is used for hypertension or oedema. The maximum effect of amiloride occurs about 6 h after an oral dose with a duration of action >24h (t1/, 21 h). The oral dose is 5-20 mg daily.
3 New England Journal of Medicine 1999 341: 709.
Triamterene (Dytac) is a potassium-sparing diuretic which has an action and use similar to that of amiloride. The diuretic effect extends over 10 h. Gastrointestinal upsets occur. Reversible, nonoliguric renal failure may occur when triamterene is used with indomethacin (and presumably other NSAIDs).
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...