Brands, Medical Use, Clinical Data
Drug Category
- Aldosterone Antagonists
- Diuretics
Dosage Forms
- Oral tablets (25 mg, 50 mg, or 100 mg)
Brands / Synonyms
Abbolactone; Acelat; Aldace; Aldactazide; Aldactide; Aldactone; Aldactone A; Alderon; Aldopur; Almatol; Altex; Aquareduct; Deverol; Diatensec; Dira; Duraspiron; Espironolactona [INN-Spanish]; Euteberol; Lacalmin; Lacdene; Laractone; Melarcon; Nefurofan; Osiren; Osyrol; Sagisal; Sincomen; SNL; Spiresis; Spiretic; Spiridon; Spiro-Tablinen; Spiroctan; Spiroctanie; Spiroderm; Spirolactone; Spirolakton; Spirolang; Spirolone; Spirone; Spironocompren; Spironolactone; Spironolactone A; Spironolactone and Hydrochlorothiazide; Spironolactone [BAN:INN:JAN]; Spironolactonum [INN-Latin]; Spironolattone [DCIT]; Sprioderm; Supra-puren; Suracton; Uractone; Urusonin; Verospiron; Verospirone; Verospirone Opianin; Xenalon
Indications
Used primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome.
Pharmacology
Spironolactone is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. 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 transgendered people. 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.
Mechanism of Action
Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule.
Absorption
Fairly rapidly absorbed from the gastrointestinal tract. Food increases the bioavailability of unmetabolized spironolactone by almost 100%.
Toxicity
The oral LD50 of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits. Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.
Biotrnasformation / Drug Metabolism
Rapidly and extensively metabolized. The metabolic pathway of spironolactone is complex and can be divided into two main routes: those in which the sulfur moiety is retained and those in which the sulfur moiety is removed by dethioacetylation. Spironolactone is transformed to a reactive metabolite that can inactivate adrenal and testicular cytochrome P450 enzymes. It also has anti-androgenic activity.
Contraindications
Aldactone is contraindicated for patients with anuria, acute renal insufficiency, significant impairment of renal
excretory function, or hyperkalemia.
Drug Interactions
ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has
been associated with severe hyperkalemia.
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.
Pressor amines (eg, norepinephrine): Spironolactone reduces the vascular responsiveness to
norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general
anesthesia while they are being treated with Aldactone.
Skeletal muscle relaxants, nondepolarizing (eg, tubocurarine): Possible increased responsiveness to
the muscle relaxant may result.
Lithium: Lithium generally should not be given with diuretics. Diuretic agents reduce the renal
clearance of lithium and add a high risk of lithium toxicity.
Nonsteroidal anti-inflammatory drugs (NSAIDs): In some patients, the administration of an NSAID can
reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing and thiazide diuretics.
Combination of NSAIDs, eg, indomethacin, with potassium-sparing diuretics has been associated with severe
hyperkalemia. Therefore, when Aldactone and NSAIDs are used concomitantly, the patient should be observed closely to
determine if the desired effect of the diuretic is obtained.
Digoxin: Spironolactone has been shown to increase the half-life of digoxin. This may result in
increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the maintenance and
digitalization doses when spironolactone is administered, and the patient should be carefully monitored to avoid
over- or underdigitalization.
Drug/Laboratory Test Interactions
Several reports of possible interference with digoxin radioimmunoassays by spironolactone, or its metabolites,
have appeared in the literature. Neither the extent nor the potential clinical significance of its interference
(which may be assay-specific) has been fully established.
|
