Reviewed by Dorothy Cooper
Dose and Administration
- 1-3 mg/kg/dose daily PO.
- Used in combination with other diuretics in the
treatment of congestive heart failure and BPD (situations of increased
Contraindications and Precautions
- Known hypersensitivity to spironolactone
- Significant impairment of renal function, especially anuria
- Caution in neonates with severe liver dysfunction
- Caution in neonates receiving potassium supplements
- Should not be used concurrently with other potassium sparing agents.
Spironolactone is a specific
pharmacological antagonist of aldosterone. Acts primarily through competitive
binding of receptors at the aldosterone dependent sodium-potassium exchange site
in the distal convoluted renal tubule. Causes increased urinary excretion of
sodium and water while potassium is retained. Also has an effect on tubular
transported calcium, resulting in increased urinary calcium excretion.
Spironolactone has moderate anti-androgenic activity in humans.
Well absorbed from the
gastrointestinal tract (bioavailability >90%). Very high protein binding (98%)
to human plasma protein. Rapidly and completely metabolised to a large number of
metabolites. The major active metabolite is canrenone which has a slow
clearance. The activity of canrenone is 10-33 % that of spironolactone.
Elimination of canrenone and other metabolites is primarily in the urine (50%)
but they also appear in bile (5-33%).
The onset of action of
spironolactone is usually observed 2-3 days after commencement of therapy. The
effects of aldosterone involve the synthesis of protein or peptide subsequent to
its combination with its receptor. The activity of the protein or peptide
persist for 2-3 days. With long-term use of spironolactone the elimination
half-life is 13-24 hours. The duration of effect persists for 2-3 days following
discontinuation of therapy.
Possible Adverse Effects
- Gastrointestinal disturbances (nausea, vomiting, diarrhoea).
- Lethargy, irritability.
- Paraesthesia, weakness, flaccid paralysis and tetany.
- Dose dependent androgenic effects (females), gynaecomastia (males).
- Monitor urea and electrolytes frequently. Anticipate
hyperkalaemia, hypocalaemia, hyponatraemia, transient elevation of urea.
- Reversible hyperchloraemic metabolic acidosis, usually in
association with hyperkalaemia, has been reported in patients with severe liver
dysfunction, even in the presence of normal renal function.
- Spironolactone has been shown to increase the elimination
half-life of digoxin. May result in increased serum
digoxin levels and
subsequent digoxin toxicity.
- 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 has been fully established.