Medications for Hypertension in Children

Adrenergic modifiers include central alpha-2-agonists, postsynaptic alpha-1-blockers, and beta-blockers (see table Oral Adrenergic Agents for Hypertension in Children).

Alpha-2-agonists (eg, clonidine) stimulate alpha-2-adrenergic receptors in the brain stem and reduce sympathetic nervous activity, lowering BP. Because they have a central action, they are more likely than other antihypertensives to cause drowsiness, lethargy, and depression; they are not widely used. Alpha-2-agonists (eg, clonidine) stimulate alpha-2-adrenergic receptors in the brain stem and reduce sympathetic nervous activity, lowering BP. Because they have a central action, they are more likely than other antihypertensives to cause drowsiness, lethargy, and depression; they are not widely used.Clonidine can be applied transdermally once a week as a patch; thus, it may be useful for patients who have difficulty adhering to therapy.

Postsynaptic alpha-1-blockers (eg, prazosin, terazosin, doxazosin) are not used for primary treatment of hypertension because evidence suggests no reduction in mortality. Postsynaptic alpha-1-blockers (eg, prazosin, terazosin, doxazosin) are not used for primary treatment of hypertension because evidence suggests no reduction in mortality.

ACE inhibitors (see table Oral ACE Inhibitors for Hypertension in Children) reduce BP by interfering with the conversion of angiotensin I to angiotensin II and by inhibiting the degradation of bradykinin, thereby decreasing peripheral vascular resistance without causing reflex tachycardia. These medications reduce BP in many patients with hypertension, regardless of plasma renin activity. Because these medications provide renal protection, they are the drugs of choice for patients with diabetes and for children with hypertension and many types of kidney disorders.

A dry, irritating cough is the most common adverse effect (much less common in children than in adults), but angioedema is the most serious and, if it affects the oropharynx, can be fatal. Angioedema is most common among Black patients and patients who smoke. ACE inhibitors may increase serum potassium and creatinine levels, especially in patients with chronic kidney disease and those taking potassium-sparing diuretics, potassium supplements, or nonsteroidal anti-inflammatory drugs (NSAIDs). ACE inhibitors are contraindicated during pregnancy and should be used with caution in adolescent females who are at risk of pregnancy. In patients with kidney disorders causing kidney dysfunction, serum creatinine and potassium levels should be checked within 2 to 4 weeks of starting therapy. If the levels are increased, then levels should be monitored at least every 3 to 6 months (more frequently if the increases are significant). ACE inhibitors can cause acute kidney injury in patients who have hypovolemia, severe heart failure, severe bilateral renal artery stenosis, or severe stenosis in the artery to a solitary kidney.

Thiazide-type diuretics enhance the antihypertensive activity of ACE inhibitors more than that of other classes of antihypertensives. Spironolactone and eplerenone also appear to enhance the effect of ACE inhibitors.Thiazide-type diuretics enhance the antihypertensive activity of ACE inhibitors more than that of other classes of antihypertensives. Spironolactone and eplerenone also appear to enhance the effect of ACE inhibitors.

ARBs (see table Oral Angiotensin II Receptor Blockers (ARBs) for Hypertension in ChildrenOral Angiotensin II Receptor Blockers (ARBs) for Hypertension in Children) block angiotensin II receptors and therefore interfere with the renin-angiotensin system as do ACE inhibitors. ARBs and ACE inhibitors are equally effective as antihypertensives. ARBs may provide added benefits via tissue ACE receptor blockade. The 2 classes have the same beneficial effects in patients with left ventricular failure or with nephropathy due to diabetes and other types of kidney diseases. An ARB should not be used together with an ACE inhibitor. ARBs may be safely started in children and adolescents with reduced renal function, but creatinine and potassium levels need to be checked in 1 to 4 weeks If the levels are increased, then levels should be monitored at least every 3 to 6 months (more frequently if the increases are significant).

Incidence of adverse events is low; angioedema occurs but much less frequently than with ACE inhibitors. Precautions for use of ARBs in patients with renovascular hypertension, hypovolemia, and severe heart failure are the same as those for ACE inhibitors (see table Oral ACE Inhibitors for Hypertension in Children). ARBs are contraindicated during pregnancy and in adolescents who may become pregnant.

CCBs (see table Oral Calcium Channel Blockers (CCBs) for Hypertension in Children) are peripheral vasodilators and reduce BP by decreasing total peripheral vascular resistance (TPR); they sometimes cause reflexive tachycardia, but these medications have minimal direct effects on the heart.

In addition to other antihypertensive effects, thiazide diuretics (see table Oral Thiazide Diuretics for Hypertension in Children) cause a small amount of vasodilation as long as intravascular volume is normal. All thiazides are equally effective in equivalent doses.

Thiazide diuretics cause potassium loss, so serum potassium should be followed until the level stabilizes. Unless serum potassium is normalized, potassium channels in the arterial walls close and the resulting vasoconstriction makes achieving the blood pressure goal difficult. Patients with potassium levels < 3.5 mEq/L (< 3.5 mmol/L) are given potassium supplements or are instructed about dietary changes that can increase potassium intake. Hypokalemia is less of a problem in children with hypertension, in whom thiazides are usually combined with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), which tend to raise potassium levels.

In most patients with diabetes, thiazide-type diuretics do not affect control of diabetes. Uncommonly, diuretics precipitate or worsen type 2 diabetes in patients with metabolic syndrome.

Direct vasodilators, including minoxidil and hydralazine (see table Direct vasodilators, including minoxidil and hydralazine (see tableOral Direct Vasodilators for Hypertension in Children), work directly on blood vessels, independently of the autonomic nervous system. Minoxidil is more potent than hydralazine but has more adverse effects, including sodium and water retention and hypertrichosis. Minoxidil should be reserved for severe, refractory hypertension.but has more adverse effects, including sodium and water retention and hypertrichosis. Minoxidil should be reserved for severe, refractory hypertension.

Hydralazine is used during pregnancy (eg, for preeclampsia) and as an adjunct antihypertensive. Long-term, high-dose (> 300 mg/day) Hydralazine is used during pregnancy (eg, for preeclampsia) and as an adjunct antihypertensive. Long-term, high-dose (> 300 mg/day)hydralazine has been associated with a drug-induced lupus syndrome, which resolves when the medication is stopped.