Spironolactone (Aldactone) -  Uses, Mechanism, Side Effects, Dosage, Overdose

Spironolactone which is marketed under the brand names Aldactone, Novo-Spiroton, Aldactazide, Spiractin, Spirotone, Verospiron or Berlactone is a diuretic and is used as an antiandrogen.
It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics, used primarily to treat heart failure, ascites in patients with liver disease, low-renin hypertension, hypokalemia, secondary hyperaldosteronism (such as occurs with hepatic cirrhosis), and Conn's syndrome (primary hyperaldosteronism). On its own, spironolactone is only a weak diuretic because its effects target the distal nephron (collecting tubule), where urine volume can only be slightly modified; but it can be combined with other diuretics to increase efficacy.
It is commonly used to treat symptoms of polycystic ovary syndrome (PCOS) such as excess facial hair and acne. It can also cause gynecomastia in males and should never be given with potassium supplementation for fear of the development of hyperkalemia.

Mechanism Of Action - How Spironolactone Acts

Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptors in the distal convoluted tubule cells (it actually works on aldosterone receptors in the collecting duct). This decreases the reabsorption of sodium and water, while decreasing the secretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop, and, so, the effect diminishes slowly.
This is because steroid pathways alter gene transcription, and it will take several days for the gene products to change (in this case the ENaC and ROMK channels will be decreased). Spironolactone has anti-androgen activity by binding to the androgen receptor and preventing it from interacting with dihydrotestosterone.

Mortality And Morbidity Benefit In Severe Heart Failure Treatment

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.
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 fewer symptoms of CHF and were hospitalized less frequently.

Availability And Packaging

It is supplied in the form of Generic Aldactone Tablets in 25mg and 100mg tablets for oral administration.
It is also available under other trade names.

Spironolactone Side 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. Because it also affects androgen receptors and other steroid receptors, 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. Spironolactone has been shown to be immunosuppressive in the treatment of sarcoidosis.

Spironolactone Dosage

Spironolactone dosing varies from patient to patient. Please follow your doctors advice.
The recommended starting spironolactone dose for severe heart failure treatment is 25 mg once daily whereas for high blood pressure treatment it is 50 mg daily.

Other Potential Benefits Of Spironolactone

It has been suggested that spironolactone can reduce the risk of Alzheimer's disease. In one study, researchers observed a reduction in the risk of Alzheimer's specifically associated with potassium-sparing diuretics. Unpublished findings from other studies, including the Gothenberg Study have suggested that higher potassium levels may be associated with a lower risk of dementia.



Considerable portions of the text here is from http://en.wikipedia.org/wiki/Spironolactone and is reproduced here under the Creative Commons Attribution-ShareAlike License