Basic Pharmacology
- Mechanism:
- Competitive inhibition of mineralocorticoid receptors
- Blockade of aldosterone-dependent sodium reabsorption
- Increased potassium retention
- Antifibrotic and antihypertrophic effects
- Classification: Potassium-sparing diuretics
- Primary agents: Spironolactone and Eplerenone
Key Indications
- Heart failure
- Primary hyperaldosteronism
- Resistant hypertension
- Edematous conditions
- Congenital adrenal hyperplasia
- Nephrotic syndrome
Spironolactone
Dosing Guidelines
- Initial dose:
- 1-3 mg/kg/day divided BID-QID
- Maximum: 100-200 mg/day based on indication
- Frequency: Daily to four times daily
- Available forms: Oral tablets, suspension
Specific Indications
- Heart Failure:
- Initial: 1-2 mg/kg/day
- Titrate based on response
- Hypertension:
- Start: 1 mg/kg/day
- Maximum: 3.3 mg/kg/day or 100 mg/day
- Edema:
- Initial: 1-3 mg/kg/day
- Adjust based on response
Unique Characteristics
- First-line mineralocorticoid antagonist
- Anti-androgenic properties
- Longer time to steady-state
- Multiple active metabolites
Eplerenone
Dosing Guidelines
- Initial dose:
- 0.5-1 mg/kg/day divided BID
- Maximum: 50-100 mg/day
- Age considerations: Limited data in <4 years
- Available forms: Oral tablets
Clinical Advantages
- More selective aldosterone blockade
- Fewer anti-androgenic effects
- Better tolerated in some patients
- Fewer drug interactions
Specific Uses
- Primary hyperaldosteronism
- Heart failure with preserved EF
- Alternative to spironolactone in:
- Adolescent males
- Patients with endocrine side effects
Clinical Use and Management
Patient Selection
- Consider in:
- Refractory heart failure
- Resistant hypertension
- Secondary hyperaldosteronism
- Protein-losing conditions
Combination Therapy
- With loop diuretics:
- Enhanced natriuresis
- Potassium balance
- Dose adjustment needed
- With ACE inhibitors/ARBs:
- Monitor potassium closely
- Risk of hyperkalemia
Special Populations
- Neonates:
- Limited data
- Close monitoring required
- Adolescents:
- Consider endocrine effects
- Gender-specific considerations
Monitoring and Safety
Laboratory Monitoring
- Baseline:
- Serum potassium
- Renal function
- Serum sodium
- Blood pressure
- Follow-up:
- 3-7 days after initiation
- With dose changes
- Periodic monitoring
Adverse Effects
- Common:
- Hyperkalemia
- Gynecomastia (spironolactone)
- Menstrual irregularities
- GI disturbances
- Serious:
- Acute kidney injury
- Severe hyperkalemia
- Endocrine disruption
Risk Mitigation
- Dietary counseling:
- Potassium intake
- Salt restrictions
- Drug interactions:
- Avoid NSAIDs
- Careful with ACEi/ARBs
- Monitor with digoxin
- Patient education:
- Warning signs
- Compliance importance
- Dietary modifications
Further Reading
