The Journal of Pediatrics
Volume 149, Issue 6 , Pages 746-754 , December 2006

Pharmacologic treatment of hypertension in children and adolescents

  • Joseph T. Flynn, MD, MS

      Affiliations

    • Division of Pediatric Nephrology, Children’s Hospital at Montefiore and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York
    • Dr Flynn is a paid consultant to AstraZeneca, Novartis, PDL BioPharma, and Pfizer.
    • Corresponding Author InformationReprint requests: Joseph T. Flynn, MD, MS, Division of Pediatric Nephrology, Montefiore Medical Center, 111 East 210th St, Bronx, NY 10467.
  • ,
  • Stephen R. Daniels, MD, PhD

      Affiliations

    • Department of Pediatrics, University of Colorado School of Medicine and The Children’s Hospital of Denver, Denver, Colorado

Received 26 April 2006 ,Revised 7 July 2006 ,Accepted 30 August 2006.

References 

  1. Gruskin AB, Dabbagh S, Fleischmann LE, Atiyeh BA. Application since 1980 of antihypertensive agents to treat pediatric disease. J Hum Hypertens. 1994;8:381–388
  2. Flynn JT. Pediatric use of antihypertensive medications: much more to learn. Curr Ther Res Clin Exp. 2001;62:314–328
  3. Public Law 105-115: Food and Drug Administration Modernization Act of 1997. Adopted November 21, 1997. Available at: http://www.fda.gov/oc/fdama/default.htm. Last accessed July 4, 2006.
  4. Wells TG. Trials of antihypertensive therapies in children. Blood Press Monit. 1999;4:189–192
  5. Shirkey H. Therapeutic orphans. J Pediatr. 1968;72:119–120
  6. Schreiner MS. Safety and effectiveness data: will children gain access?. Am Heartt J. 1998;136:4–5
  7. Physicians’ Desk Reference. 54th ed. Montvale, NJ: Medical Economics Company; 2000;
  8. Blumer JL. Off-label drug use in children. Pediatrics. 1999;104:598–602
  9. Nahata MC. Lack of pediatric drug formulations. Pediatrics. 1999;104:607–609
  10. Nahata MC, Morosco RS, Hipple TF. Stability of amlodipine besylate in two liquid dosage forms. J Am Pharm Assoc. 1999;39:375–377
  11. Thompson KC, Zhao Z, Mazakas JM, Beasley CA, Reed RA, Moser CL. Characterization of an extemporaneous liquid formulation of lisinopril. Am J Health Syst Pharm. 2003;60:69–74
  12. Flynn JT. Successes and shortcomings of the FDA Modernization Act. Am J Hypertens. 2003;16:889–891
  13. Public Law 107-109: Best Pharmaceuticals for Children Act. Adopted January 4, 2002. Available at: http://www.fda.gov/cder/pediatric/#bpca. Last accessed July 4, 2006.
  14. US Food and Drug Administration. Center for Drug Evaluation and Research. Approved active moieties for which FDA has issued a written request for pediatric studies under Section 3 of the Best Pharmaceuticals for Children Act. Available at: http://www.fda.gov/cder/pediatric/offpatwrlist.htm. Last accessed July 4, 2006.
  15. Public Law No: 108-155: Pediatric Research Equity Act of 2003. Adopted January 7, 2003. Available at: http://www.fda.gov/cder/pediatric/#prea. Last accessed July 4, 2006.
  16. Steinbrook R. Testing medications in children. N Engl J Med. 2002;347:1462–1470
  17. Roberts R, Rodriguez W, Murphy D, Crescenzi T. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. J Am Med Assoc. 2003;290:905–911
  18. US Food and Drug Administration. Center for Drug Evaluation and Research. Pediatric exclusivity labeling changes. Available at: http://www.fda.gov/cder/pediatric/labelchange.htm. last accessed July 4, 2006.
  19. Sakarcan A, Tenney F, Wilson JT, Stewart JJ, Adcock KG, Wells TG, et al. The pharmacokinetics of irbesartan in hypertensive children and adolescents. J Clin Pharmacol. 2001;41:742–749
  20. Sorof JM, Cargo P, Graepel J, Humphrey D, King E, Rolf C, et al. Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial. Pediatr Nephrol. 2002;17:345–350
  21. Wells T, Frame V, Soffer B, Shaw W, Zhang Z, Herrera P, et al. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension. J Clin Pharmacol. 2002;42:870–880
  22. Trachtman H, Frank R, Mahan JD, Portman R, Restaino I, Matoo TK, et al. Clinical trial of extended-release felodipine in pediatric essential hypertension. Pediatr Nephrol. 2003;18:548–553
  23. Blumer JL, Daniels SR, Dreyer WJ, Batisky D, Walson PD, Roman D, et al. Pharmacokinetics of quinapril in children: assessment during substitution for chronic angiotensin-converting enzyme inhibitor treatment. J Clin Pharmacol. 2003;43:128–132
  24. Soffer B, Zhang Z, Miller K, Vogt BA, Shahinfar S. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension. Am J Hypertens. 2003;16:795–800
  25. Li JS, Berezny K, Kilaru R, Hazan L, Portman R, Hogg R, et al. Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children?. Hypertension. 2004;44:289–293
  26. Flynn JT, Newburger JW, Daniels SR, Sanders SP, Portman RJ, Hogg RJ. A randomized, placebo-controlled trial of amlodipine in children with hypertension. J Pediatr. 2004;145:353–359
  27. Falkner B, Sugg J, Sorof J, Kilbaner M. Efficacy and safety of a long-acting beta blocker, extended release metoprolol succinate, in hypertensive children [abstract]. Am J Hypertens. 2005;18(5Part2):8A
  28. Shahinfar S, Cano F, Soffer BA, Ahmed T, Santoro EP, Zhang Z, et al. A double-blind, dose–response study of losartan in hypertensive children. Am J Hypertens. 2005;18:183–190
  29. US Food and Drug Administration. Summaries of medical and clinical pharmacology reviews of pediatric studies. Available at: http://www.fda.gov/cder/pediatric/Summaryreview.htm. Last accessed July 4, 2006.
  30. Wilson JT. An update on the therapeutic orphan. Pediatrics. 1999;104;:585–590
  31. Ellis D, Moritz ML, Vats A, Janosky JE. Antihypertensive and renoprotective efficacy and safety of losartan (A long-term study in children with renal disorders). Am J Hypertens. 2004;17:928–935
  32. Sorof JM, Urbina EM, Cunningham RJ, Hogg RJ, Moxey-Mims M, Eissa MA, et al. Screening for eligibility in the study of antihypertensive medication in children: experience from the Ziac Pediatric Hypertension Study. Am J Hypertens. 2001;14:783–787
  33. Falkner B, Lowenthal DT, Affrime MB. The pharmacodynamic effectiveness of metoprolol in adolescent hypertension. Pediatr Pharmacol. 1982;2:49–55
  34. Flynn JT, Pasko DA. Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension. Pediatr Nephrol. 2000;15:302–316
  35. Parker ML, Robinson RF, Nahata MC. Amlodipine therapy in pediatric patients with hypertension. J Am Pharm Assoc. 2002;42:114–117
  36. Sinaiko AR. Treatment of hypertension in children. Pediatr Nephrol. 1994;8:603–609
  37. 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. Bethesda, Md: National Institutes of Health, NIH publication; 2005;05:5267
  38. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA. 2004;291:2847–2850
  39. Stevens VJ, Obarzanek E, Cook NR, Lee IM, Appel LJ, Smith West D, et al. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann Intern Med. 2001;134:1–11
  40. Appel L, Brands M, Daniels SR, Karanja N, Elmer P, Sacks F. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47:296–308
  41. Strong WB, Malina RM, Blimkie CJR, Daniels SR, Dishman RK, Gutin B, et al. Evidence based physical activity for school-age youth. J Pediatr. 2005;146:732–737
  42. Ribeiro MM, Silva AG, Santos NS, Guazzelle I, Matos LN, Trombetta IC, et al. Diet and exercise training restore blood pressure and vasodilatory responses during physiological maneuvers in obese children. Circulation. 2005;111:1915–1923
  43. Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, et al. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation. 2005;111:1999–2012
  44. Lawes CM, Vander Hoorn S, Law MR, Elliott P, MacMahon S, Rodgers A. Blood pressure and the global burden of disease 2000 (Part II: estimates of attributable burden). J Hypertens. 2006;24:423–430
  45. Hsu CY, McCulloch CE, Darbinian J, Go AS, Iribarren C. Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease. Arch Intern Med. 2005;165:923–928
  46. Ellis EN. Diabetes mellitus and the kidney in adolescents. Adolesc Med Clin. 2005;16:173–184
  47. Shatat IF, Flynn JT. Hypertension in children with chronic kidney disease. Adv Chronic Kidney Dis. 2005;12:378–384
  48. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981–2997
  49. Laragh JH. Abstract, closing summary, and table of contents for Laragh’s 25 lessons in pathophysiology and 12 clinical pearls for treating hypertension. Am J Hypertens. 2001;14:1173–1177
  50. Flynn JT, Alderman MH. Characteristics of children with primary hypertension seen at a referral center. Pediatr Nephrol. 2005;20:961–966
  51. Kavey RE, Cotton JL, Blackman MS. Atenolol therapy for exercise-induced hypertension after aortic coarctation repair. Am J Cardiol. 1990;66:1233–1236
  52. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–2572
  53. After the diagnosis: adherence and persistence with hypertension therapy. Am J Manag Care. 2005;11(13 Suppl):S395–S399
  54. Task Force on Blood Pressure Control in Children. Report of the second Task Force on Blood Pressure Control in Children—1987 (National Heart, Lung, and Blood Institute, Bethesda, Maryland). Pediatrics. 1987;79:1
  55. Wells T, Stowe C. An approach to the use of antihypertensive drugs in children and adolescents. Curr Ther Res Clin Exp. 2001;62:329
  56. Woroniecki RP, Flynn JT. How are hypertensive children evaluated and managed? (A survey of North American pediatric nephrologists). Pediatr Nephrol. 2005;20:791–797
  57. Halme L, Vesalainen R, Kaaja M, Kantola I. Self-monitoring of blood pressure promotes achievement of blood pressure target in primary health care. Am J Hypertens. 2005;18:1415–1420
  58. Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354:2443–2451

PII: S0022-3476(06)00837-7

doi: 10.1016/j.jpeds.2006.08.074

The Journal of Pediatrics
Volume 149, Issue 6 , Pages 746-754 , December 2006