Spironolactone
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Spironolactone
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| Systematic (IUPAC) name | |
| 7α-acetylthio-3-oxo-17α-pregn-4-ene-21,17-carbolactone | |
| Identifiers | |
| CAS number | |
| ATC code | C03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C24H32O4S |
| Mol. mass | 416.574 g/mol |
| SMILES | search in , |
| Synonyms | Aldactone Spirotone Spirolactone |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | Hepatic |
| Half life | 10 minutes |
| Excretion | Urine, Bile |
| Therapeutic considerations | |
| Pregnancy cat. |
C (USA); B3 (Aus) |
| Legal status |
PoM |
| Routes | PO only |
Spironolactone (marketed as Aldactone®, Novo-Spiroton®, Spiractin®, Spirotone®, or Berlactone®) is a synthetic steroid which is commonly used as a diuretic or as an antiandrogen.
It is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics, used primarily to treat ascites in patients with liver disease, low-renin hypertension, hypokalemia, and Conn's syndrome. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. About one person in one hundred with hypertension has elevated levels of aldosterone; in these persons the antihypertensive effect of spironolactone may exceed that of complex combined regimens of other antihypertensives. Due to its anti-androgen effect, it can also be used to treat hirsutism, and is a common component in hormone therapy for male-to-female Transsexual and transgendered people. It is also used for treating hair loss and acne in women.
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[edit] Mechanism of action
Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells. This increases the secretion of water and sodium, while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly. Spironolactone has anti-androgen activity by binding to the androgen receptor and thus preventing it to interact with dihydrotestosterone.[1]
[edit] Pharmacokinetics
Spironolactone is fairly rapidly absorbed from the gastrointestinal tract. It is also rapidly metabolised and bound in plasma proteins. Many of its metabolites are also active and one of them, canrenone as potassium canrenoate, is used parenterally when rapid effect is needed. Spironolactone's half-life is 85 minutes, but canrenone's half-life is 10 to 35 hours, depending on the dose. The main elimination route is in the urine and some also in the bile.
[edit] Mortality and morbidity benefit in severe CHF
Spironolactone was shown to have a significant mortality and morbidity benefit in the Randomized Aldactone Evaluation Study (RALES), which studied people with severe congestive heart failure (New York Heart Association functional class III or IV).[2] Patients in the study arm of the trial (those receiving spironolactone) had a relative risk of death (when compared to the placebo group) equal to 0.70 or a 30% relative risk reduction. Patients in the study arm also had significantly less symptoms of CHF and were hospitalized less frequently.
[edit] Adverse effects and interactions
Spironolactone is associated with an increased risk of bleeding from the stomach and duodenum, but a causal relationship between the two has not been established.[3] Since it also affects steroid receptors elsewhere in the body, it can cause gynecomastia, menstrual irregularities and testicular atrophy. Other side effects include ataxia, erectile dysfunction, drowsiness and rashes. A carcinogenic effect has been demonstrated in rats.[4]
People using this drug should avoid salt substitutes containing potassium.[5]
[edit] See also
[edit] References
- ^ Berardesca, E; Gabba P, Ucci G, Borroni G, Rabbiosi G. (1988). "Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris.". Int J Tissue React. 10 (2): 115-119. PMID 2972662. Retrieved on 2007-03-15.
- ^ Pitt B, Zannad F, Remme W, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999). "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.". N Engl J Med 341 (10): 709-17. PMID 10471456.
- ^ Verhamme KMC, Mosis G, Dieleman JP, et al. (2006). "Spironolactone and risk of upper gastrointestinal events: population based case-control study". Brit Med J 333 (7563): 330–3. DOI:10.1136/bmj.38883.479549.2F.
- ^ Aldactone Monograph: Warnings, Precautions. rxlist.com. Retrieved on 2007-03-15.
- ^ Advisory Statement (pdf). Klinge Chemicals / LoSalt. Retrieved on 2007-03-15.
[edit] External links
| Antihypertensives (C02) and diuretics (C03) | |
|---|---|
| Antiadrenergic agents (including alpha) | Clonidine, Doxazosin, Guanethidine, Guanfacine, Lofexidine,Mecamylamine, Methyldopa, Moxonidine, Prazosin, Rescinnamine, Reserpine |
| Vasodilators | Diazoxide, Hydralazine, Minoxidil, Nitroprusside, Phentolamine |
| Other antihypertensives | Bosentan, Ketanserin |
| Low ceiling diuretics | Bendroflumethiazide, Chlorothiazide, Chlortalidone, Hydrochlorothiazide, Indapamide, Quinethazone, Mersalyl, Metolazone, Theobromine, Cicletanine |
| High ceiling diuretics | Bumetanide, Furosemide, Torasemide |
| Potassium-sparing diuretics | Amiloride, Eplerenone, Spironolactone, Triamterene |
