Angiotensin Receptor Blockers
Introduction
- Alternative to ACE inhibitors with better tolerability profile
- Common agents: Losartan, Valsartan, Candesartan, Irbesartan
- Fewer side effects compared to ACE inhibitors
- FDA-approved options for pediatric hypertension
Mechanism of Action
ARBs work through selective blockade of the renin-angiotensin system:
- Selective blockade of AT1 receptors
- Direct inhibition of angiotensin II effects
- No effect on bradykinin metabolism
- Compensatory increase in plasma renin activity
Physiologic Effects
- Selective vasodilation of resistance vessels
- Reduction in aldosterone secretion
- Decreased sodium reabsorption
- Anti-inflammatory and anti-fibrotic effects
- Improved endothelial function
- Regression of vascular and cardiac hypertrophy
Clinical Indications
Primary Indications
- Primary and secondary hypertension
- Heart failure (especially with ACE inhibitor intolerance)
- Proteinuric kidney diseases
- Marfan syndrome
- Post-cardiac transplantation
Specific Clinical Scenarios
- ACE inhibitor-induced cough
- History of angioedema with ACE inhibitors
- Chronic kidney disease with proteinuria
- Diabetic nephropathy
- Fontan circulation
Advantages Over ACE Inhibitors
- No increase in bradykinin levels
- Lower incidence of cough
- Reduced risk of angioedema
- Better tolerability profile
- More complete blockade of AT1 receptor effects
Dosing Guidelines
Losartan
- Initial: 0.7 mg/kg/day (up to 50 mg daily)
- Frequency: Once or twice daily
- Maximum: 1.4 mg/kg/day up to 100 mg daily
- Age restriction: ≥6 years for hypertension
Valsartan
- Initial: 1.3 mg/kg/day (up to 40 mg daily)
- Frequency: Once daily
- Maximum: 2.7 mg/kg/day up to 160 mg daily
- Age restriction: ≥6 years for hypertension
Candesartan
- Initial: 0.02 mg/kg/day (up to 4 mg daily)
- Frequency: Once daily
- Maximum: 0.4 mg/kg/day up to 32 mg daily
- Note: Approved for heart failure in adults
Special Dosing Considerations
- Start at lower doses in volume-depleted patients
- Adjust dose based on renal function
- Consider twice-daily dosing in proteinuric conditions
- May need higher doses for proteinuria reduction
Monitoring & Safety
Required Monitoring
- Baseline: Blood pressure, serum creatinine, potassium, CBC
- Follow-up: Blood pressure at 2-4 weeks
- Regular monitoring: Creatinine, potassium every 3-6 months
- Growth and development in chronic therapy
- Urine protein/creatinine ratio in proteinuric conditions
Adverse Effects
- Hypotension (especially first-dose)
- Hyperkalemia
- Acute kidney injury
- Dizziness and headache
- Rarely: Angioedema
Contraindications
- Pregnancy (teratogenic)
- Bilateral renal artery stenosis
- Severe hepatic impairment
- Hyperkalemia
- Volume depletion
Clinical Pearls
- Monitor liver function with concurrent medications
- Consider drug interactions with NSAIDs
- Watch for hyperkalemia with potassium supplements
- May need temporary discontinuation during acute illness
- Monitor closely in patients with renal impairment
Drug Interactions
- NSAIDs: Increased risk of renal dysfunction
- Potassium supplements: Risk of hyperkalemia
- Lithium: Increased lithium levels
- Diuretics: Enhanced hypotensive effect
