The calcium channel blockers (CCBs) are a diverse group of antihypertensive medications with variable pharmacokinetics and clinical effects. Although CCBs have been widely applied to the treatment of hypertensive children, data regarding the pharmacokinetics, efficacy and safety of these agents in children are extremely limited. In this review we briefly summarize the mechanism of action of CCBs and then summarize pertinent pharmacokinetic information on each of the CCBs commonly used in children, including amlodipine, diltiazem, felodipine, isradipine, intravenous nicardipine, nifedipine and verapamil. Clinically important drug interactions and adverse effects are discussed, as well as the potential role of CCBs in renal protection. Available pediatric efficacy and safety data are summarized, and recommendations made regarding the rational use of CCBs in the management of pediatric hypertension.

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Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension

A randomized, placebo-controlled trial of amlodipine in children with hypertension

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07±0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%–50% every 5–7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29±0.11 mg/kg per day for those <13 years, 0.16±0.11 mg/kg per day for those ≥13 years, 0.23±0.14 mg/kg per day for essential, hypertension and 0.24±0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.

Efficacy of amlodipine in pediatric patients with hypertension

Treatment of hypertensive children with amlodipine

Improved recognition of the relationship between childhood and adult blood pressures and identification of end-organ damage in children, adolescents, and young adults with hypertension has led to increased focus by pediatricians and general practitioners on the detection, evaluation, and treatment of hypertension. Notably, detection, evaluation, and treatment of pediatric hypertension has increased significantly since the first Task Force Report on High Blood Pressure in Children and Adolescents in 1977 with advances in both nonpharmacologic and pharmacologic treatments. Angiotensin-converting enzyme inhibitors (e.g. captopril, enalapril, lisinopril, ramipril) and calcium channel antagonists (e.g. nifedipine, amlodipine, felodipine, isradipine) are the most commonly prescribed antihypertensive medications in children due to their low adverse-effect profiles. Diuretics (e.g. thiazide diuretics, loop diuretics, and potassium-sparing diuretics) are usually reserved as adjunct therapy. Newer agents, such as angiotensin receptor antagonists (e.g. irbesartan), are currently being studied in children and adolescents. These agents may be an option in children with chronic cough secondary to angiotensin-converting enzyme inhibitors. β-Adrenoreceptor antagonists (e.g. propranolol, atenolol, metoprolol, and labetalol), α-adrenoreceptor antagonists, α-adrenoreceptor agonists, direct vasodilators, peripheral adrenoreceptor neuron agonists, and combination products are less commonly used in pediatric patients because of adverse events but may be an option in children unresponsive to calcium channel blockers, angiotensin converting-enzyme inhibitors, or angiotensin receptor blockers.

Pharmacologic treatment of chronic pediatric hypertension.

The calcium antagonist amlodipine may have the potential for expanded use in children owing to its physiochemistry and pharmacokinetic profile that facilitates once-daily dosing in a liquid formulation. Its safety and efficacy have not been previously evaluated in children. A retrospective analysis of 15 pediatric bone marrow transplant patients who had amlodipine incorporated into their antihypertensive drug regimen reveals significantly lower blood pressure as compared with baseline therapy (123.5+/-2.1 mmHg and 117.2+/-2.2 mmHg, systolic blood pressure before and during amlodipine, P<0.05; 81.5+/-1.8 mmHg and 75.5+/-2.6 mmHg, diastolic blood pressure before and during amlodipine, P<0.05). Amlodipine provided improved blood pressure control in this cohort and may provide a valuable pharmacologic alternative for treatment of pediatric hypertension.

J. W. Rogan

Papers

Efficacy of Amlodipine in Pediatric Bone Marrow Transplant Patients