Immediate drug treatment is typically started (along with lifestyle changes) for children with
Symptomatic hypertension at any stage or level
Stage 1 hypertension with any evidence of end-organ dysfunction or damage
Stage 2 hypertension even with an obvious, modifiable risk factor (eg, obesity), which should be addressed while blood pressure (BP) is being controlled
Any stage of hypertension if they have chronic kidney disease, diabetes, or cardiac disease
In children with high normal or borderline hypertension or stage 1 hypertension without symptoms or end-organ dysfunction, lifestyle changes are initiated, and if these do not sufficiently lower BP within about 6 months, drug treatment will be necessary (1).
Generally, drug treatment should begin with a single drug at the low end of its dosing range and increased every 1 to 4 weeks until BP is controlled, the upper end of the dosing range is approached, or adverse effects develop that affect the use of the drug. At that point, if the BP goal has not been attained, a second drug can be added and titrated as with the initial drug. Classes of oral drugs used to treat hypertension include
Adrenergic modifiers (beta- and alpha-antagonist, alpha-2-agonist, beta-blocker)
Oral therapy for persistent hypertension in children should generally begin with an ACE inhibitor or a CCB. (ARBs are equally effective and do not cause a cough, but there are more data in children on the use of ACE inhibitors.) Both classes of drugs can be given as a single daily dose and seem to be equally effective. ACE inhibitors should be used in patients with chronic kidney disease or diabetes because these drugs may also protect the kidneys. CCBs should be used in menstruating girls if there is risk of pregnancy because ACE inhibitors and ARBs have significant effects on a fetus. CCBs also have no significant effect on blood chemistries. Thiazide diuretics have been used as initial treatment, but salt intake in adolescents is usually so high that they are rarely effective.
If initial therapy with a single drug does not achieve the target BP, a second drug should be added. If the first drug is an ACE inhibitor or ARB, thiazide diuretics have proved to work well as second drugs, but a CCB could be added instead. If the first drug is a CCB, then an ACE inhibitor or an ARB usually works as a second drug, but if there is a risk of pregnancy, they need to be avoided, and a thiazide diuretic or other drug can be tried instead. If a thiazide diuretic is used, chlorthalidone is the ideal one to use because it can be given once a day. Except in special conditions, vasodilators and alpha- and beta-blockers are 3rd-line drugs, which if needed should be used after consultation with a specialist.
Many antihypertensives can be obtained or prepared as oral suspensions for children who cannot take pills or capsules and when nonstandard doses are needed.
Загальне посилання
1. Flynn JT, Kaelber DC, Baker-Smith CM, et al: Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140(3):e20171904, 2017. doi: 10.1542/peds.2017-1904
Адренергічні модифікатори
Adrenergic modifiers include central alpha-2-agonists, postsynaptic alpha-1-blockers, and peripheral-acting nonselective adrenergic 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 no longer widely used. Clonidine can be applied transdermally once a week as a patch; thus, it may be useful for nonadherent patients.
Postsynaptic alpha-1-blockers (eg, prazosin, terazosin, doxazosin) are no longer used for primary treatment of hypertension because evidence suggests no reduction in mortality.
Пероральні адренергічні засоби для лікування гіпертонії у дітей
Drug (Class) | Dose | Some Adverse Effects | Comments |
|---|---|---|---|
Atenolol (beta-blocker) | Initial dose: 0.5–1 mg/kg once a day (or 0.25–0.5 mg/kg twice a day) up to maximum daily dose 2 mg/kg (not to exceed 100 mg) | May cause bradycardia or AV block, or fatigue/lethargy, dizziness, or wheezing | Contraindications include pulmonary edema and cardiogenic shock. Use with caution in patients with diabetes and asthma. Atenolol should not be abruptly stopped. |
Clonidine (alpha-2-agonist) | For children < 12 years of age: Initial dose 2.5–5 mcg/kg twice a day (or 1.7–3.3 mcg/kg 3 times a day), maximum total daily dose 0.9 mg For children ≥ 12 years of age: Initial dose 0.1 mg twice a day, can be increased in increments of 0.05 twice a day at weekly intervals, up to maximum dose 1.2 mg twice a day For children stabilized on an oral dose, may switch to a transdermal patch delivering the same total daily dose; change every 5 to 7 days | Drowsiness, fatigue, dizziness | Clonidine should not be abruptly stopped. |
Labetalol (mixed alpha- and beta-blocker) | Initial dose: 0.5–1.5 mg/kg twice a day up to 100 mg twice a day, maximum dose 6 mg/kg (not to exceed 600 mg) twice a day | Orthostatic hypotension, edema, bradycardia, heart failure, bronchospasm | Contraindications include pulmonary edema, cardiogenic shock, or heart block. Use with caution in patients with asthma or hepatic disease. |
Інгібітори ангіотензинперетворюючого ферменту (АПФ)
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 drugs reduce BP in many hypertensive patients, regardless of plasma renin activity. Because these drugs provide renal protection, they are the drugs of choice for patients with diabetes and for hypertensive children with many types of kidney disorders.
A dry, irritating cough is the most common adverse effect (much less common in children than in older patients), but angioedema is the most serious and, if it affects the oropharynx, can be fatal. Angioedema is most common among blacks and smokers. 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 renal disorders causing renal dysfunction, serum creatinine and potassium levels should be checked within 2 to 4 weeks of starting therapy. If the levels are increased, then they 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.
Пероральні інгібітори АПФ при гіпертонії у дітей
Drug | Dose | Some Adverse Effects | Comments |
|---|---|---|---|
Captopril | For neonates: Initial dose 0.01–0.05 mg/kg once a day to a maximum of 0.5 mg/kg 4 times a day For younger children: Initial dose 0.2–0.5 mg/kg 2 to 4 times a day, or for older children 6.25–12.5 mg 2 to 4 times a day (maximum daily dose 6 mg/kg) For adolescents: 12.5–25 mg 2 to 4 times a day (maximum daily dose 150 mg) | Common adverse effects: Cough, headache, dizziness Severe adverse effects: Fetal toxicity, hyperkalemia, acute kidney injury, angioedema | Contraindications include pregnancy and history of angioedema. Dosage adjustments are needed for children who have renal dysfunction. Compliance with captopril may be improved with maximum dosing 3 times a day instead of 4. |
Enalapril | For infants and children: Initial dose 0.08 mg/kg once a day (maximum daily dose 0.6 mg/kg or 5 mg) For adolescents: Initial dose 2.5–5 mg once a day (maximum daily dose 40 mg) | ||
Lisinopril | For children < 6 years of age: Limited data For children ≥ 6 years of age: Initial dose 0.07 mg/kg once a day with a maximum initial daily dose of 5 mg (titrated to a maximum daily dose of 40 mg once a day) | ||
ACE = angiotensin-converting enzyme. | |||
Блокатори рецепторів ангіотензину II (БРА)
ARBs (see table Oral 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 they 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.
Пероральні блокатори рецепторів ангіотензину II (БРА) для лікування гіпертонії у дітей
Drug | Dose | Some Adverse Effects | Comments |
|---|---|---|---|
Candesartan | For children 1–5 years of age: Initial dose 0.2 mg/kg once a day (up to a maximum dose of 0.4 mg/kg once a day or 0.2 mg/kg twice a day) For children ≥ 6 years who weigh < 50 kg: Initial dose 4 mg once a day up to a maximum dose 16 mg once a day (or 8 mg twice a day) For children ≥ 6 years who weigh ≥ 50 kg: Initial dose 8 mg once a day up to a maximum dose of 32 mg once a day (or 16 mg twice a day) | Common adverse effects: Headache, dizziness Severe adverse effects: Fetal toxicity, hyperkalemia, acute kidney injury | Contraindications include pregnancy and angioedema. The blood pressure–lowering ability of ARBs is equal to that of angiotensin-converting enzyme inhibitors (which are usually used first because there is more clinical experience). ARBs do not cause cough, and angioedema is less frequent. ARBs are usually given once a day, but twice daily dosing at a lower dose may be considered when an adverse effect, such as dizziness resulting from hypotension, occurs after a single larger daily dose. |
Losartan | For children ≥ 6 years of age: Initial dose 0.7 mg/kg once a day up to 50 mg once a day. Titrate up to a maximum daily dose of 1.4 mg/kg not to exceed 100 mg (alternatively 0.7 mg/kg or 50 mg twice a day) | ||
Valsartan | For children ≥ 6 years of age: Initial dose 1.3 mg/kg once a day (maximum initial dose 40 mg once a day); maximum daily dose 2.7 mg/kg not to exceed 160 mg once a day |
Блокатори кальцієвих каналів (БКК)
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 drugs have minimal direct effects on the heart.
Пероральні блокатори кальцієвих каналів (БКК) для лікування гіпертензії у дітей
Drug* | Dose | Some Adverse Effects | Comments |
|---|---|---|---|
Amlodipine | For children 1–5 years of age: Initial dose 0.1 mg/kg once a day, up to a maximum dose 0.6 mg/kg (not to exceed 5 mg) once a day For children ≥ 6 years of age: Initial dose 2.5 mg once a day, up to a maximum dose 10 mg once a day | Common adverse effects: Flushing, dizziness, peripheral edema Severe adverse effects: Angioedema | Contraindications include hypersensitivity to CCBs. |
Isradipine | Extended-release tablet: Initial dose 2.5 mg once a day, up to maximum dose 10 mg once a day | ||
Nifedipine, extended-release† | Initial dose: 0.25–0.5 mg/kg once a day up to maximum dose 3 mg/kg (not to exceed 120 mg) once a day (or 1.5 mg/kg or 60 mg twice a day) | ||
* All of these drugs are dihydropyridines, which have mainly vascular effects and minimal cardiac effects. | |||
† Nifedipine immediate-release tablet is no longer recommended because of the potential for rapid blood pressure drop. | |||
Тіазидні діуретики
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 hypertensive children, 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.
Пероральні тіазидні діуретики при гіпертонії у дітей
Drug | Dose | Some Adverse Effects | Comments |
|---|---|---|---|
Chlorthalidone | Initial dose: 0.3 mg/kg once a day, up to a maximum dose 2 mg/kg or 50 mg once a day | Common adverse effects: Dizziness, hypokalemia, increased blood glucose, alkalosis Severe adverse effects: Cardiac dysrhythmias, cholestatic jaundice, pancreatitis | Contraindications include end stage renal disease and anuria. Because chlorthalidone has a longer duration of action, it may be best for chronic hypertension where a single daily dose may help with adherence. Chlorothiazide and hydrochlorothiazide should typically be given twice a day because of their shorter duration of action. |
Chlorothiazide | For children < 2 years of age: Initial dose 10 mg/kg once a day or 5 mg/kg twice a day (maximum initial dose 20 mg/kg) up to a maximum dose of 375 mg once a day (or 175 mg twice a day) For children 2–12 years of age: Initial dose 10 mg/kg once a day or 5 mg/kg twice a day, up to a maximum daily dose 20 mg/kg (not to exceed 1000 mg) once a day (or 10 mg/kg or 500 mg twice a day) | ||
Hydrochlorothiazide | For children ≥ 6 months of age: Initial dose 1 mg/kg once a day or 0.5 mg twice a day, up to a maximum daily dose of 2 mg/kg (not to exceed 37.5 mg) once a day (or 1 mg/kg or 18 mg twice a day) |
Судинорозширювальні засоби
Direct vasodilators, including minoxidil and hydralazine (see table Oral 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.
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 drug is stopped.
Пероральні судинорозширювальні засоби для лікування гіпертонії у дітей
Drug | Dose | Some Adverse Effects | Comments |
|---|---|---|---|
Hydralazine | In infants and children: Initial dose 0.375–0.5 mg/kg twice a day or 0.187–0.25 mg/kg 4 times a day up to maximum daily total dose in infants 5 mg/kg and in children maximum daily total dose 7.5 mg/kg (not to exceed 200 mg) | Headache, dizziness, and reflex tachycardia | Use with caution in severe renal and cardiac disease. Dosage adjustments are needed for children who have renal dysfunction. |
Minoxidil | For children < 12 years of age: Initial dose 0.1–0.2 mg/kg (not to exceed 5 mg) once a day increased as needed up to 0.33 mg/kg 3 times a day, maximum daily total dose 50 mg For children ≥ 12 years of age: Initial dose 5 mg once a day, increased as needed up to 20 mg twice a day (or 12.5 mg 3 times a day), effective range 10–40 mg/day | Common adverse effects: Dizziness, hypertrichosis, reflex tachycardia, fluid retention Severe adverse effects: Heart failure, pulmonary edema, Stevens-Johnson syndrome | Contraindicated in acute myocardial infarction or pheochromocytoma. This drug causes significant reflex tachycardia and fluid retention, so may need to be used with a beta-blocker and diuretic. Dosage adjustments are needed for children who have renal dysfunction. |
