Spironolactone is a steroid that is chemically related to the mineralocorticoid aldosterone. It is hence an aldosterone antagonist.
It acts from the interstitial side of the tubular cell, where it binds with the receptor and inhibits the formation of Aldosterone-induced proteins in a competitive manner.
It is metabolized in the liver and kidneys and excreted in the urine.
Mechanism of action.
· An aldosterone antagonist that competitively binds to receptors at the aldosterone-dependent Na-K exchange site in the distal tubules.
· This results in increased excretion of Na+, Cl-, and water and retention of K+ and H+ in the body.
· It has no effect on Na+ and K+ transport in the absence of Aldosterone, while under normal conditions increases Na+ and decreases K+ secretion.
· Also increases testosterone clearance and estradiol production by blocking the conversion of potent androgens to weaker ones in the peripheral tissues.
Clinical uses.
- To counteract K+ loss due to thiazide and loop diuretics.
- Edema: in cirrhotic and nephrotic edema where aldosterone levels are high.
- Hypertension: Used as adjuvant to thiazide to prevent hypokalaemia.
- Congestive heart failure: As an additional drug to conventional therapy in moderate to severe CHF.
Drug interaction.
- When administered together with K+ supplements— hyperkalemia can occur.
- Aspirin blocks spironolactone action by inhibiting the tubular secretion of its active metabolite canrenone.
- More pronounced hyperkalemia can occur in patients receiving ACE inhibitors/ARBs.
- Spironolactone increases plasma digoxin concentration.
Adverse effects.
- Drowsiness, ataxia, mental confusion, epigastric distress, and loose motions.
- Hyperkalaemia and acidosis.
- Gastric bleeding.
- Inability to achieve and maintain an erection.
- Thrombocytopenia, urticaria, and fever.
- Electrolyte disturbances.
- Reduced libido.
Contraindication.
- Patients with liver cirrhosis.
- Peptic ulcers.
- Addison’s disease
- Hypersensitivity to the drug.
Dosage.
- 25–50 mg BD–QID; max 400 mg/day
- ALDACTONE 25, 50, 100 mg tablets.
- ALDACTIDE: Spironolactone 25 mg + hydroflumethiazide 25mg tablet LACILACTONE,
- SPIROMIDE: Spironolactone 50 mg+ furosemide 20 mg tablet .
- TORLACTONE Spironolactone 50 mg + torasemide 10 mg tablet.
