Potassium-Sparing Diuretics Spironolactone
Indication
Spironolactone is used in the management of edema associated with congestive heart failure, hepatic cirrhosis, and nephrotic syndrome. It is also used to treat hypertension, hypokalemia, and primary aldosteronism. Spironolactone has also been associated with increased success in the treatment of patients with congestive heart failure who undergo antialdosterone therapy.
Mechanism of Action
Spironolactone is a potassium-sparing diuretic that competes with aldosterone for binding to receptor sites in the distal tubule of the kidneys. It increases the excretion of sodium, chloride, and water and inhibits the excretion of potassium and hydrogen. The effect of aldosterone on arteriolar smooth muscle may also be blocked.
Dosing
Spironolactone is only available for oral/enteral administration.
Neonates:
Diuretic: 1 to 3 mg/kg/day divided every 12 to 24 hours
Children:
Diuretic, hypertension: 1.5 to 3.5 mg/kg/day or 60mg/m2/day in one to four divided doses daily
Adults:
Edema, hypokalemia: 25 to 200 mg/day in one to two divided doses
Hypertension: 25 to 50 mg/day in one to two doses daily
Pharmacokinetics
Spironolactone is well absorbed after oral administration, with bioavailability at approximately 90%. The protein binding of the drug ranges from 91 to 98%, with hepatic metabolism to multiple metabolites, including the active agent, canrenone. The half-life of spironolactone is 78 to 84 minutes and the half-life of canrenone is 13 to 24 hours. The duration of action is 2 to 3 days.
Monitoring parameters: potassium, sodium, renal function
Contraindications: anuria, hyperkalemia, renal failure
Precautions/Adverse Effects
Warning: severe hyperkalemia may result when used with angiotensin-converting enzyme inhibitors, potassium supplements, and NSAIDs; monitor potassium levels and renal function closely.
Use with caution in patients with decreased renal function, hyponatremia, dehydration, or reduced hepatic function.
Adverse reactions associated with spironolactone include hyperkalemia, dehydration, hyponatremia, hyperchloremic metabolic alkalosis, headaches, fever, diarrhea, vomiting, nausea, lethargy, rash, anorexia, gynecomastia (in males), amenorrhea, agranulocytosis, and decreased renal function.
Poisoning Information
Symptoms of spironolactone overdose include lethargy, fatigue, drowsiness, dizziness, confusion, nausea, and vomiting. Dehydration, electrolyte imbalance, and severe hyperkalemia may occur with large doses. Treatment of the hyperkalemia is with I.V. glucose and insulin, and possibly sodium bicarbonate.
Drug-Drug Interactions
Hyperkalemia may occur when spironolactone is used with angiotensin-converting enzyme inhibitors, NSAIDs, potassium supplements, or other potassium-sparing diuretics. Spironolactone use may decrease clearance of digoxin; may cause a decreased response to norepinephrine; and may decrease the effects of oral anticoagulants.
This post has been viewed 914 times.
Comments are closed.
