Clinical pharmacology of converting enzyme inhibitors, calcium channel blockers and diuretics

The predominant trend in pediatric antihypertensive management is towards increasing reliance on angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers because of their general effectiveness, low incidence of adverse reactions and potential specific benefit in patients with renal disease. The common aetiological relationship between renal disease and elevated BP also is the reason that diuretic therapy continues to be included in many treatment regimens. A number of ACE inhibitors are available for clinical use, although only captopril has been subjected to any meaningful degree of investigation in children. Initial doses of captopril are 0.5 mg/kg in children > 6 months of age and 0.01-0.1 mg/kg in neonates, because of an apparent increased antihypertensive effect and duration of action in this age group. Side-effects are few and the major adverse effect is a reduction in glomerular filtration in patients with bilateral renal artery stenosis. The calcium channel blockers reduce cytosolic calcium concentration and are particularly effective in patients with volume dependent forms of hypertension. The pharmacokinetic properties of these drugs are similar with drug clearance by hepatic metabolism. In particular, nifedipine has a rapid onset of action and is widely used to treat hypertensive emergencies. Although it has been used sublingually, the effectiveness of the drug is due to absorption from the gastrointestinal tract. Few side-effects from these drugs have been reported in children. Heart rate and cardiac output increase but return to pretreatment levels within a few weeks. As is the case with the ACE inhibitors, calcium channel blockers appear to have a positive effect on renal function.