Pediatric Hypertension Medication
- Author: Edwin Rodriguez-Cruz, MD; Chief Editor: P Syamasundar Rao, MD more...
Drugs currently used to treat hypertensive emergencies include nicardipine, labetalol, and sodium nitroprusside.
Many antihypertensive drugs are available for the treatment of chronic hypertension. The choice of drug is usually based on the mode of action and the potential for adverse effects. From a pharmacologic point of view, antihypertensive drugs may be classified in the following categories:
Diuretics, which block sodium reabsorption at various levels of the renal tubules
Adrenergic blockers, which act by competitively inhibiting the catecholamines
Direct vasodilators, which act by means of various mechanisms
Angiotensin-converting enzyme (ACE) inhibitors, which block the conversion of angiotensin I to angiotensin II
Angiotensin II receptor blockers (ARBs), which interfere with the binding of angiotensin II to angiotensin I receptors
Calcium-channel blockers, which block the entry of calcium into the cells, producing vasodilation
Angiotensin-Converting Enzyme (ACE) Inhibitors
ACE inhibitors prevent conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and lower aldosterone secretion. They are effective and well-tolerated drugs with no adverse effects on plasma lipid levels or glucose tolerance. They prevent the progression of diabetic nephropathy and other forms of glomerulopathies but appear to be less effective in black patients than in white patients.
Patients with high plasma renin activity may have an excessive hypotensive response to ACE inhibitors. Patients with bilateral renal vascular disease or with single kidneys, whose renal perfusion is maintained by high levels of angiotensin II, may develop irreversible acute renal failure when treated with ACE inhibitors.
ACE inhibitors are contraindicated in pregnancy. Cough and angioedema are less common with newer members of this class than with captopril. Serum potassium and serum creatinine concentrations should be monitored for the development of hyperkalemia and azotemia. Examples of agents from this class include captopril, lisinopril, and enalapril.
Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
Rapidly absorbed, but bioavailability is significantly reduced with food intake. It achieves a peak concentration in an hour and has a short half-life. The drug is cleared by the kidney. Impaired renal function requires reduction of dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.
Can be started at low dose and titrated upward as needed and as patient tolerates.
Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It helps control blood pressure (BP) and proteinuria. It decreases the pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance.
Enalapril has a favorable clinical effect when administered over a long period. It helps prevent potassium loss in distal tubules. The body conserves potassium; thus, less oral potassium supplementation is needed.
Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Benazepril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
When pediatric patients are unable to swallow tablets or the calculated dose does not correspond with tablet strength, an extemporaneous suspension can be compounded. Combine 300 mg (15 tablets of 20-mg strength) in 75 mL of Ora-Plus suspending vehicle, and shake well for at least 2 minutes. Let the tabs sit and dissolve for at least 1 hour, then shake again for 1 minute. Add 75 mL of Ora-Sweet. The final concentration is 2 mg/mL, with a total volume of 150 mL. The expiration time is 30 days with refrigeration.
Fosinopril is a competitive ACE inhibitor. It prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.
Quinapril is a competitive ACE inhibitor. It reduces angiotensin II levels, decreasing aldosterone secretion.
Beta-blockers are especially useful in the concurrent treatment of hypertension and migraine. Dosing is limited by the bradycardia adverse effect. Drugs of this class should not be prescribed to athletes, because their athletic performance may be compromised. This class should not be used in patients with insulin-dependent diabetes, because these drugs blunt the normal warning symptoms of hypoglycemia.
Noncardioselective agents (ie, agents that elicit beta1 and beta2 blockade, eg, propranolol) are contraindicated in asthma and heart failure, due to their ability to cause bradycardia and bronchospastic actions. Selective beta1 -adrenergic blockers include atenolol and metoprolol. Labetalol elicits a mixed alpha and beta blockade. Another agent from this class is propranolol.
Atenolol is used to treat hypertension. It selectively blocks beta1-receptors, with little or no effect on beta2 types. Beta-adrenergic blocking agents affect blood pressure via multiple mechanisms.
Actions include a negative chronotropic effect that decreases heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the central nervous system (CNS), and suppression of renin release from the kidneys. Atenolol is used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure.
Beta-adrenergic blockers reduce the inotropic state of the left ventricle, decrease diastolic dysfunction, and increase left ventricular compliance, thereby reducing the pressure gradient across the left ventricular outflow tract. Atenolol decreases the heart rate, thus reducing myocardial oxygen consumption and reducing myocardial ischemia potential. During intravenous (IV) administration, carefully monitor BP, heart rate, and electrocardiography (ECG).
Labetalol blocks beta1-adrenergic, alpha-adrenergic, and beta2-adrenergic receptor sites, decreasing blood pressure.
Metoprolol is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG.
Propranolol has membrane-stabilizing activity and decreases the automaticity of contractions. It is not suitable for emergency treatment of hypertension. Do not give it IV in hypertensive emergencies.
This combination of a beta-blocker and a diuretic includes a selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions.
Thiazide diuretics inhibit the reabsorption of sodium in the distal tubules, increasing the excretion of sodium, water, and potassium and hydrogen ions. They have been effective in treating hypertension of various etiologies. Besides diminishing sodium reabsorption, they also appear to diminish the sensitivity of blood vessels to circulating vasopressor substances. In all patients treated with diuretics, electrolyte levels should be monitored. Examples of thiazide diuretics are hydrochlorothiazide and chlorthalidone.
Hydrochlorothiazide inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as of potassium and hydrogen ions.
Chlorthalidone inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as of potassium and hydrogen ions.
Loop diuretics inhibit the reabsorption of sodium chloride in the thick ascending limb of the loop of Henle. They can be used to treat hypertension in patients with renal insufficiency; they are less effective than thiazide diuretics in patients who are hypertensive with normal renal function. Examples of loop diuretics are furosemide and bumetanide.
Furosemide is a loop diuretic that increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule. It increases renal blood flow without increasing the filtration rate. The onset of action is generally within 1 hour. Furosemide increases potassium, sodium, calcium, and magnesium excretion.
The dose must be individualized to the patient. Depending on the response, administer furosemide at increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until the desired diuresis occurs. When treating infants, titrate with 1 mg/kg/dose increments until a satisfactory effect is achieved.
Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) and in treating hypertension; their diuretic action causes decreased blood volume.
Bumetanide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in the ascending loop of Henle. These effects increase the urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs after administration, renal vascular resistance decreases, and renal blood flow is enhanced. In terms of effect, 1 mg of bumetanide is equivalent to approximately 40 mg of furosemide.
Potassium-sparing diuretics are used alone or in combination with other diuretics to prevent or correct hypokalemia. However, these drugs can cause hyperkalemia, particularly when given to patients with renal insufficiency or administered in combination with ACE inhibitors and ARBs. Examples of potassium-sparing diuretics are spironolactone and amiloride.
Spironolactone is used for management of hypertension. It may block the effects of aldosterone on arteriolar smooth muscle.
Amiloride is a potassium-conserving (antikaliuretic) pyrazine-carbonyl-guanidine that is chemically unrelated to other known antikaliuretic or diuretic agents. It possesses weak (compared with thiazide diuretics) natriuretic, diuretic, and antihypertensive activity. In some clinical studies, its activity increased the effects of thiazide diuretics. Amiloride is not an aldosterone antagonist, and its effects are observed even in the absence of aldosterone.
Amiloride exerts its potassium-sparing effect through inhibition of sodium reabsorption at the distal convoluted tubule, the cortical collecting tubule, and the collecting duct. This decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion.
Amiloride usually begins to act within 2 hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6 and 10 hours and lasts about 24 hours. Peak plasma levels are obtained in 3-4 hours, and plasma half-life ranges from 6 to 9 hours.
Amiloride is not metabolized by the liver and is excreted unchanged by the kidneys. About 50% of a dose of amiloride is excreted in urine and 40% in stool within 72 hours. The drug has little effect on glomerular filtration rate (GFR) or renal blood flow. Because the liver does not metabolize amiloride, drug accumulation is not anticipated in patients with hepatic dysfunction; however, accumulation can occur if hepatorenal syndrome develops.
Amiloride should rarely be used alone. When used as single agents, potassium-sparing diuretics, including amiloride, result in an increased risk of hyperkalemia (approximately 10% with amiloride). This agent should be used alone only when persistent hypokalemia has been documented and only with careful titration of the dose and close monitoring of serum electrolytes.
Calcium-channel blockers affect BP by decreasing vascular peripheral resistance. With short-acting calcium-channel blockers, the cardiac response to this action is variable, resulting in tachycardia. Long-acting preparations may cause a decrease in the heart rate.
Calcium-channel blockers are classified by their structure, and they have different degrees of selectivity in their effects on vascular smooth muscle. The dihydropyridines do not exert electrophysiologic effects and are commonly used to manage hypertension. Facial flushing may occur. Examples of calcium-channel blockers are include amlodipine and isradipine.
Amlodipine is generally regarded as a dihydropyridine, although experimental evidence suggests that it also may bind to nondihydropyridine binding sites. It is appropriate for the prophylaxis of variant angina and has antianginal and antihypertensive effects. Amlodipine blocks the postexcitation release of calcium ions into cardiac and vascular smooth muscle, thereby inhibiting the action of adenosine triphosphatase (ATPase) on myofibril contraction.
The overall effect is reduced intracellular calcium levels in cardiac and smooth-muscle cells of the coronary and peripheral vasculature, resulting in dilatation of coronary and peripheral arteries. Amlodipine also increases myocardial oxygen delivery in patients with vasospastic angina, and it may potentiate ACE inhibitor effects.
During depolarization, amlodipine inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. It benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. It has a substantially longer half-life than nifedipine and diltiazem and is administered once daily.
Felodipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. It benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. It can be used during pregnancy if clinically indicated.
Calcium-channel blockers potentiate ACE inhibitor effects. Renal protection is not proven, but these agents reduce morbidity and mortality rates in congestive heart failure. Calcium-channel blockers are indicated in patients with diastolic dysfunction. They are effective as monotherapy in black patients and elderly patients.
Isradipine is a dihydropyridine calcium-channel blocker. It inhibits calcium from entering select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization. This causes relaxation of coronary vascular smooth muscle, which results in coronary vasodilation. Vasodilation reduces systemic resistance and blood pressure, with a small increase in resting heart rate. Isradipine also has negative inotropic effects.
Extended-release nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery. Sublingual administration is generally safe, despite theoretical concerns.
Angiotensin II Receptor Blockers (ARBs)
ARBs lower BP by blocking the final receptor (ie, angiotensin II) in the renin-angiotensin axis. Like ACE inhibitors, they are contraindicated in pregnancy. Serum electrolyte and creatinine levels should be monitored. Examples of ARBs are irbesartan and losartan.
Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at the tissue receptor site. It may induce a more complete inhibition of renin-angiotensin system than ACE inhibitors do, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema.
Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of renin-angiotensin system than ACE inhibitors do, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. It is suitable for patients unable to tolerate ACE inhibitors.
Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to angiotensin I receptors in vascular smooth muscle. Its action is independent of the pathways for angiotensin II synthesis.
Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from angiotensin I receptors and may lower blood pressure by antagonizing angiotensin I-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.
Valsartan may induce a more complete inhibition of renin-angiotensin system than ACE inhibitors do, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. It is suitable for patients unable to tolerate ACE inhibitors.
Alpha2 Agonists, Central-Acting
Central alpha-agonists lower BP by stimulating alpha2 -adrenergic receptors in the brainstem and activate inhibitory neurons, causing decreased vasomotor tone and heart rate. This class of drugs may cause dry mouth or sedation. Caution is warranted in patients with cerebrovascular disease, coronary insufficiency, sinus-node dysfunction, or renal impairment. A transdermal patch is available.
Sudden discontinuance of central alpha-agonists may lead to severe rebound hypertension. These drugs have been used in the past for the treatment of children with attention deficit hyperactivity disorder (ADHD) and still may be used successfully in patients with ADHD who also have hypertension. An example of a central alpha-agonist is clonidine.
Clonidine is a central alpha-adrenergic agonist that stimulates alpha2-adrenoreceptors in the brainstem and activates inhibitory neurons, causing decreases in vasomotor tone and heart rate.
These drugs act directly on the smooth muscle in the peripheral vasculature to cause vasodilation. Tachycardia and fluid retention are common side effects. Prolonged use of minoxidil can cause hypertrichosis. Hydralazine can cause a lupuslike syndrome in certain populations of slow acetylators. Examples of direct vasodilators are minoxidil and hydralazine.
Minoxidil relaxes arteriolar smooth muscle, causing vasodilation, which, in turn, may reduce blood pressure.
Hydralazine decreases systemic resistance through direct vasodilation of arterioles. It is used to treat hypertensive emergencies. The use of a vasodilator will reduce systemic vascular resistance, which, in turn, may allow forward flow, improving cardiac output.
Peripheral alpha-antagonists inhibit postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and decreasing total peripheral resistance and BP. These drugs often cause marked hypotension after the first dose. High doses are likely to cause postural hypotension. Of the peripheral alpha-antagonists, doxazosin and terazosin are selective for alpha1 -receptors. Prazosin is nonselective and inhibits both alpha1 - and alpha2 -receptors.
Doxazosin, a quinazoline compound, is a selective alpha1-adrenergic antagonist. It inhibits postsynaptic alpha-adrenergic receptors, causing vasodilation of veins and arterioles and decreases total peripheral resistance and BP.
Prazosin treats prostatic hypertrophy. It improves urine flow rates through relaxation of smooth muscle, accomplished by blocking alpha1-adrenoceptors in the bladder neck and prostate. When increasing the dose, administer the first dose of each increment at bedtime to reduce syncopal episodes. Although doses higher than 20 mg/day usually do not increase efficacy, some patients may benefit from doses as high as 40 mg/day.
Terazosin decreases arterial tone by allowing peripheral postsynaptic blockade. It has minimal alpha2 effect.
[Guideline] Task Force. Report of the Second Task Force on Blood Pressure Control in Children--1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics. 1987 Jan. 79(1):1-25. [Medline].
[Guideline] Task Force. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control. Pediatrics. 1996 Oct. 98(4 Pt 1):649-58. [Medline].
[Guideline] NHLBI. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004 Aug. 114(2 Suppl 4th Report):555-76. [Medline]. [Full Text].
Gruskin AB. Factors affecting blood pressure. Drukker A, Gruskin AB, eds. Pediatric Nephrology: Pediatric and Adolescent Medicine. 3rd ed. Basel, Switzerland: Karger; 1995. 1097.
Gavrilovici C, Boiculese LV, Brumariu O, Dimitriu AG. [Etiology and blood pressure patterns in secondary hypertension in children]. Rev Med Chir Soc Med Nat Iasi. 2007 Jan-Mar. 111(1):70-81. [Medline].
Kapur G, Ahmed M, Pan C, Mitsnefes M, Chiang M, Mattoo TK. Secondary hypertension in overweight and stage 1 hypertensive children: a Midwest Pediatric Nephrology Consortium report. J Clin Hypertens (Greenwich). 2010 Jan. 12(1):34-9. [Medline].
Sun SS, Grave GD, Siervogel RM, Pickoff AA, Arslanian SS, Daniels SR. Systolic blood pressure in childhood predicts hypertension and metabolic syndrome later in life. Pediatrics. 2007 Feb. 119 (2):237-46. [Medline].
Banker A, Gupta-Malhotra M, Syamasundar Rao P. Childhood hypertension: a review. J Hypertens. Dec 2013. 2(4):128. [Full Text].
Dhuper S, Buddhe S, Patel S. Managing Cardiovascular Risk in Overweight Children and Adolescents. Paediatr Drugs. 2013 Apr 12. [Medline].
Hanevold C, Waller J, Daniels S, Portman R, Sorof J. The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children: a collaborative study of the International Pediatric Hypertension Association. Pediatrics. 2004 Feb. 113(2):328-33. [Medline].
Leung LC, Sung RY, So HK, et al. Prevalence and risk factors for hypertension in Hong Kong Chinese adolescents: waist circumference predicts hypertension, exercise decreases risk. Arch Dis Child. 2011 Sep. 96(9):804-9. [Medline].
Rao PS, Seib PM. Coarctation of the Aorta. Medscape Drugs & Diseases from WebMD. Available at http://emedicine.medscape.com/article/895502-overview. Updated Sep 25, 2014; Accessed: July 17, 2015.
[Guideline] University of Michigan Health System. Essential hypertension. Ann Arbor (MI): University of Michigan Health System; 2009 Feb. [Full Text].
Meyers RS, Siu A. Pharmacotherapy Review of Chronic Pediatric Hypertension. Clin Ther. 2011 Oct 7. [Medline].
Schaefer F, Litwin M, Zachwieja J, Zurowska A, Turi S, Grosso A, et al. Efficacy and safety of valsartan compared to enalapril in hypertensive children: a 12-week, randomized, double-blind, parallel-group study. J Hypertens. 2011 Oct 21. [Medline].
Sezer SS, Narin N, Ozyurt A, et al. Cardiovascular changes in children with coarctation of the aorta treated by endovascular stenting. J Hum Hypertens. 2014 Jun. 28(6):372-7. [Medline].
Forbes TJ, Kim DW, Du W, et al, for the CCISC Investigators. Comparison of surgical, stent, and balloon angioplasty treatment of native coarctation of the aorta: an observational study by the CCISC (Congenital Cardiovascular Interventional Study Consortium). J Am Coll Cardiol. 2011 Dec 13. 58 (25):2664-74. [Medline].
Aeberli I, Spinas GA, Lehmann R, l'Allemand D, Molinari L, Zimmermann MB. Diet determines features of the metabolic syndrome in 6- to 14-year-old children. Int J Vitam Nutr Res. 2009 Jan. 79(1):14-23. [Medline].
Gonzalez-Juanatey JR, Paz FL, Eiras S, Teijeira-Fernandez E. [Adipokines as novel cardiovascular disease markers. Pathological and clinical considerations]. Rev Esp Cardiol. 2009 Jun. 62 Suppl 2:9-16. [Medline].
Kshatriya S, Reams GP, Spear RM, Freeman RH, Dietz JR, Villarreal D. Obesity hypertension: the emerging role of leptin in renal and cardiovascular dyshomeostasis. Curr Opin Nephrol Hypertens. 2009 Oct 21. [Medline].
Nakamura Y, Ueshima H, Okuda N, et al. Relation of serum leptin to blood pressure of Japanese in Japan and Japanese-Americans in Hawaii. Hypertension. 2009 Dec. 54(6):1416-22. [Medline].
Moledina S, Pandya B, Bartsota M, Mortensen KH, McMillan M, Quyam S, et al. Prognostic Significance of Cardiac Magnetic Resonance Imaging in Children with Pulmonary Hypertension. Circ Cardiovasc Imaging. 2013 Apr 9. [Medline].
Maxey DM, Ivy DD, Ogawa MT, Feinstein JA. Food and Drug Administration (FDA) Postmarket Reported Side Effects and Adverse Events Associated with Pulmonary Hypertension Therapy in Pediatric Patients. Pediatr Cardiol. 2013 Mar 27. [Medline].
|Age, y||95th BP Percentile for Girls, mm Hg||95th BP Percentile for Boys, mm Hg|
|50th Height Percentile||75th Height Percentile||50th Height Percentile||75th Height Percentile|
|1-6 y||7-12 y|
|Thrombosis of renal artery or vein
Congenital renal anomalies
Coarctation of aorta
|Renal artery stenosis
Renal parenchymal disease
Coarctation of aorta
|Renal parenchymal disease
Renal parenchymal disease