What are the alternative drug options for pediatric hypertension when Angiotensin Receptor Blockers (ARBs) and Calcium Channel Blockers (CCBs) are not suitable?

Drug Options for Pediatric Hypertension Beyond ARBs and CCBs

For pediatric hypertension, when ARBs and CCBs are not suitable, the recommended alternative drug options include ACE inhibitors, thiazide diuretics, and beta-blockers, with ACE inhibitors being the preferred choice for most children. 1

First-Line Alternatives

ACE Inhibitors

• ACE inhibitors are recommended as first-line therapy for children with hypertension, especially those under 55 years of age 1
• They are particularly beneficial in children with chronic kidney disease, diabetes mellitus, or proteinuria 1
• Examples include lisinopril, enalapril, and captopril 2, 3
• ACE inhibitors have demonstrated efficacy in pediatric patients with favorable safety profiles 4
• Contraindicated in females of childbearing potential due to teratogenic effects 1

Thiazide-like Diuretics

• Thiazide diuretics are recommended when CCBs are not suitable or in patients with evidence of heart failure 1
• Chlorthalidone (12.5-25.0 mg once daily) or indapamide (1.5 mg modified-release once daily or 2.5 mg once daily) are preferred over conventional thiazides like hydrochlorothiazide 1
• Usually reserved as adjunct therapy in combination with other antihypertensive medications 3

Second-Line Options

Beta-Blockers

• Beta-blockers may be considered in younger patients, particularly those with intolerance to ACE inhibitors and ARBs 1
• Metoprolol has shown efficacy in reducing systolic blood pressure in pediatric patients 5
• Not preferred as initial therapy due to their expanded adverse effect profile compared to other agents 6
• Common side effects include growth impairment, school performance issues, depression, fatigue, bradycardia, hypotension, and sleep disturbances 6
• If beta-blockers are started and a second drug is required, add a CCB rather than a thiazide-like diuretic to reduce the risk of developing diabetes 1

Special Considerations

Combination Therapy

• If blood pressure is not controlled with monotherapy, combination therapy may be necessary 1
• The combination of an ACE inhibitor or ARB with a thiazide-like diuretic is commonly used 1
• Bisoprolol/hydrochlorothiazide combination has shown efficacy in reducing diastolic blood pressure in pediatric patients 5

Medication Selection Based on Comorbidities

• For children with chronic kidney disease: ACE inhibitors or ARBs are strongly recommended as first-line agents 1
• For children with diabetes mellitus or proteinuria: ACE inhibitors or ARBs are preferred 1
• For children with asthma or reactive airway disease: Avoid non-selective beta-blockers due to risk of bronchospasm 6

Treatment Goals and Monitoring

• Goal blood pressure is <90th percentile for age, or <130/80 mm Hg, whichever is lower (based on office/casual BP readings) 1
• For children with chronic kidney disease, the recommended goal is a 24-hour mean arterial pressure <50th percentile 1
• Regular monitoring for side effects is essential, particularly for:
  • Growth in young children on beta-blockers 6
  • Academic performance and cognitive function 6
  • Depression and mood changes, particularly in adolescents on beta-blockers 6
  • Heart rate and blood pressure 6

Pitfalls and Caveats

• ACE inhibitors and ARBs are contraindicated in pregnancy and females of childbearing potential 1
• Beta-blockers can mask hypoglycemic symptoms in diabetic patients 6
• Infants are particularly susceptible to hypoglycemia when on beta-blockers 6
• Non-selective beta-blockers have a higher risk of bronchospasm and increased airway resistance 6
• Start with lower doses and titrate slowly, especially with beta-blockers, to minimize adverse effects 6