Substance-Induced Hypertension: Mechanisms and Management

  • Douglas L. BloweyEmail author
Reference work entry


In most children elevated blood p ressure measurements are transient and due to situational anxiety. When the blood pressure elevations persist, most children are found not to have an identifiable cause for the hypertension. In the minority of children, hypertension is due to an identifiable cause which may include a variety of medications and illicit substances. Substance-induced hypertension can be associated with unexpected and severe blood pressure elevations and should be considered in such circumstances. Fortunately, the blood pressure typically returns to normal values soon after stopping the offending agent, and usually pharmacologic intervention is not required.


Hypertension Children Substance-induced Stimulants Illicit drugs Club drugs NSAIDs Phenylephrine Pseudoephedrine Anti-VEGF 


  1. DHHS Publication 2016–1232: http://www.cdc/nchs/hus/contents2015.htm#79. Retrieved 25 Oct 2016
  2. 2016 HHS Publication No. SMA16-4984 (2016) Center for Behavioral Health Statistics and Quality: Retrieved 25 Oct 2016
  3. Aljadhey H, Tu W, Hansen R, Blalock S, Brater DC, Murray M (2012) Comparative effects of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure in patients with hypertension. BMC Cardiovasc Disord 12(1):93PubMedPubMedCentralCrossRefGoogle Scholar
  4. Aw T, Haas S, Liew D, Krum H (2005) Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure. Arch Intern Med 165(5):490–496PubMedCrossRefGoogle Scholar
  5. Bayorth M, Zukowska-Grojec Z, Palkovits M, IJ K (1984) Effect of phencyclidine (PCP) on blood pressure and catecholamine levels in discrete brain nuclei. Brain Res 321(2):315–318CrossRefGoogle Scholar
  6. Bender J, Adamson P, Reid J, Xu L, Baruchel S, Shaked Y, … Yamashiro D (2008) Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: a children’s oncology group study. J Clin Oncol 26(3):399–405CrossRefGoogle Scholar
  7. Benesch M, Windelberg M, Sauseng W, Witt V, Fleischhack G, Lacker H, … Urban C (2007) Compassionate use of bevacizumab (Avastin) in children and young adults with refractory or recurrent solid tumors. Ann Oncol 19(4):807–813PubMedCrossRefGoogle Scholar
  8. Benowitz N, Sharp D (1989) Inverse relationship between serum cotinine concentrations and blood pressure in cigarette smokers. Circulation 80(5):1309–1312PubMedCrossRefGoogle Scholar
  9. Bexis S, Docherty J (2006) Effects of MDMA, MDA, MDAE on blood pressure, heart rate, locomotor activity and body temperature in the rat involve alpha-adrenoceptors. BJCP 147(8):926–934Google Scholar
  10. Bey T, Patel A (2007) Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug. Western J Emerg Med 8(1):9–14Google Scholar
  11. Branum A, Rossen L, Schoendorf K (2014) Trends in caffeine intake among US children and adolescents. Pediatrics 133(3):386–393PubMedPubMedCentralCrossRefGoogle Scholar
  12. Clark L (1985) Alcohol-induced hypertension: mechanisms, complications, and clinical implications. J Natl Med Assoc 77(5):385–389PubMedPubMedCentralGoogle Scholar
  13. Cooper A, Egleston C (1997) Accidental ingestion of ecstasy by a toddler: unusual cause for convulsion in a febrile child. J Accid Emerg Med 14(3):183–184PubMedPubMedCentralCrossRefGoogle Scholar
  14. De La Torre R, Farre M, Roset P, Hernandez Lopez C, Ortuno M, Menoyo E, … Cami J (2000) Pharmacology of MDMA in humans. Ann N Y Acad Sci 33(1):225–237Google Scholar
  15. Eisenbert M, Mendelson J, Evans G, Jue J, Jones R, Schiller N (1993) Left ventricular function immediately after intravenous cocaine: a quantitative two-dimensional echocardiographic study. JACC 22(6):1581–1586CrossRefGoogle Scholar
  16. Emergency Department Data (2011) The Drug Abuse Network: Retrieved 25 Oct 2016
  17. Fanari Z, Kennedy K, Lim M, Laddu A, Stolker J (2014) Comparison of in-hospital outcomes for beta-blocker use versus non-beta blocker use in patients presenting with cocaine-associated chest pain. Am J Cardiol 113(11):1802–1806PubMedCrossRefGoogle Scholar
  18. Feinstein J, Feudtner C, Kempe A (2014) Adverse drug event-related emergency department visits associated with complex chronic conditions. Pediatrics 133:e1575–e1585PubMedCrossRefGoogle Scholar
  19. Feudtner C, Dai D (2012) Prevalence of polypharmacy exposure among hospitalized children in the United States. Arch Pediatr Adolesc Med 166(1):9–16PubMedCrossRefGoogle Scholar
  20. Freese T, Miotto K, Reback C (2002) The effects and consequences of selected club drugs. J Subst Abus Treat 23(2):151–156CrossRefGoogle Scholar
  21. Givens M, Wald R, Schafer J, Wians F, Delaney K (2007) Prevalence of cocaine use in ED patients with severe hypertension. Am J Emerg Med 25(6):612–615PubMedCrossRefGoogle Scholar
  22. Gouzoulis E, von Bardeleben U, Rupp A, Kovar K, Hermle L (1993) Neuroendocrine and cardiovascular effects of MDE in healthy volunteers. Neuropsychopharmacology 8(3):187–193PubMedCrossRefGoogle Scholar
  23. Grace F, Sculthorpe N, Baker J, Davies B (2003) Blood pressure and rate pressure product response in males using high-dose anabolic androgenic steroids (AAS). J Sci Med Sport 6(3):307–312PubMedCrossRefGoogle Scholar
  24. Gupta-Malhotra M, Banker A, Shete S, Hashmi S, Tyson J, Barratt M, … Boerwinkle E (2015). Essential hypertension vs. secondary hypertension among children. Am J Hypertens 28(1):73–80PubMedPubMedCentralCrossRefGoogle Scholar
  25. Gururangan S, Chi S, Poussaint T, Onar-Thomas A, Gilbertson R, Vajapeyam S, … Kun L (2012) Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a pediatric brain tumor consortium study. J Clin Oncol 28(18):3069–3075.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Hatton R, Winterstein A, McKelvey R, Shuster J, Hendeles L (2007) Efficacy and safety of oral phenylephrine: systematic review and meta-analysis. Ann Pharmacother 41(3):381–390PubMedCrossRefGoogle Scholar
  27. Hayman S, Leung N, Grande J, Garovic D (2012) VEGF inhibition, hypertension, and renal toxicity. Curr Oncol Rep 14(4):285–294PubMedPubMedCentralCrossRefGoogle Scholar
  28. Health, United States, 2015: With Special Feature on Racial and Ethnic Health Disparities. (n.d.). Center for Disease Control and Prevention: www.cdc/nchs/hus/2015/079.pdf. Retrieved 27 Oct 2016
  29. Husain K, Ansari R, Ferder L (2014) Alcohol-induced hypertension: mechanism and prevention. World J Cardiol 6(5):245–252PubMedPubMedCentralCrossRefGoogle Scholar
  30. Hwang E, Jakacki R, Fisher M, Kilburn L, Horn M, Vezina G, Rood BR, Packer R (2013) Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas. Pediatr Blood Cancer 60(5):776–782PubMedCrossRefGoogle Scholar
  31. Hysek C, Schmid Y, Rickli A, Simmler L, Donzelli M, Grouzmann E, Liechti M (2012) Carvedilol inhibits the cardiostimulant and thermogenic effects of in humans. Br J Pharmacol 166(8):2277–2288PubMedPubMedCentralCrossRefGoogle Scholar
  32. Jee S, He J, Whelton P, Suh I, Klag M (1999) The effect of chronic coffee drinking on blood pressure a meta-analysis of controlled clinical trials. Hypertension 33(2):647–652PubMedCrossRefGoogle Scholar
  33. Johnson A, Nguyen T, Day R (1994) Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med 121(14):289–300PubMedCrossRefGoogle Scholar
  34. Johnson D, Hisel T, Phillips B (2003) Effect of cyclooxygenase-2 inhibitors on blood pressure. Ann Pharmacother 37(3):442–446PubMedCrossRefGoogle Scholar
  35. Karp H, Kaufman N, Anand S (1980) Phencyclidine poisoning in young children. J Pediatr 97(6):1006–1009PubMedCrossRefGoogle Scholar
  36. Kernan W, Viscoli C, Brass L (2000) Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 343(25):1826–1832PubMedCrossRefGoogle Scholar
  37. Kim A, Dombi E, Tepas K, Fox E, Martin S, Wolters P, … Widemann B (2012) Phase 1 trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type 1 and plexiform neurofibromas. Pediatr Blood Cancer 60(3):396–401CrossRefGoogle Scholar
  38. Kontak A, Victor R, Vongpatanasin W (2013) Dexmedetomidine as a novel countermeasure for cocaine-induced central sympathoexcitation in cocaine-addicted humans. Hypertension 61(2):388–394PubMedCrossRefGoogle Scholar
  39. Lange R, Hillis L (2001) Cardiovascular complications of cocaine use. N Engl J Med 345(5):351–358PubMedCrossRefGoogle Scholar
  40. McCord J, Jneid H, Hollander J, de Lemos J, Cercek B, Hsue P, … Newby K (2008) Management of Cocaine-associated chest pain and myocardial infarction. A scientific statement from the American Heart Association and cardiac care committee of the council on clinical cardiology. Circulation 117(14):1897–1907PubMedCrossRefGoogle Scholar
  41. McDaniel C, Miotto K (2011) Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies. J Psychoactive Drugs 33(2):143–149CrossRefGoogle Scholar
  42. Melian A, Burillo-Putze G, Campo C, Padron A, Ramos C (2004) Accidental ecstasy poisoning in a toddler. Pediatr Emerg Care 20(8):534–535PubMedCrossRefGoogle Scholar
  43. Menon D, Wang Z, Fadel P, Arbique D, Leonard D, Li J, … Vongpatanasin W (2007) Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans. J Am Coll Cardiol 50(7):626–633PubMedCrossRefGoogle Scholar
  44. Mir O, Ropert S, Alexandre J, Goldwasser F (2009) Hypertension as a surrogate marker for the activity of anti-VEGF agents. Ann Oncol 20(5):967–970PubMedCrossRefGoogle Scholar
  45. Nehlig A, Daval J-L, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic, and psychostimulant effects. Brain Res Rev 17(2):139–170PubMedCrossRefGoogle Scholar
  46. Noordzij M, Uiterwaal C, Arends L, Kok F, Grobbee D, Geleijnse J (2005) Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens 23:921–928PubMedCrossRefGoogle Scholar
  47. Papathanasiou G, Zerva E, Zacharis I, Papandreou M, Papageorgiou E, Tzima C, … Evangelou A (2016) Association of high blood pressure with body mass index, smoking and physical activity in healthy young adults. Open Cardiovasc Med J 9:5–17PubMedPubMedCentralCrossRefGoogle Scholar
  48. Rakic V, Burke V, Beilin J (1999) Effects of coffee on ambulatory blood pressure in older men and women: a randomized controlled trial. Hypertension 33(3):869–873PubMedCrossRefGoogle Scholar
  49. Reismuller B, Azuzi A, Peyrl A, Heinrich M, Gruber-Olipitz M, Luckner D, … Slavc I (2010) Feasibility and tolerability of bevacizumab in children with primary CNS tumors. Pediatr Blood Cancer 54(5):681–686Google Scholar
  50. Richards J, Garber D, Laurin E, Albertson T, Derlet R, Amsterdam E, … Lange R (2016) Treatment of cocaine cardiovascular toxicity: a systematic review. Clin Toxicol 1–20Google Scholar
  51. Rimm E, Klatsky A, Grobbee D, Stampfer M (1996) Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits? BMJ 312(7033):731–736PubMedPubMedCentralCrossRefGoogle Scholar
  52. Russell A, Schwartz R, Dawling S (1992) Accidental ingestion of ‘ecstasy’ (3,4-methylenedioxymethylamphetamine). Arch Dis Child 67(19):1114–1115CrossRefGoogle Scholar
  53. Salerno S, Jackson J, Berbano E (2005) Effect of oral pseudoephedrine on blood pressure and heart rate. Arch Intern Med 165(5):1686–1694PubMedCrossRefGoogle Scholar
  54. Samuels J, Franco K, Wan F, Sorof J (2006) Effect of stimulants on 24-hour ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial. Pediatr Nephrol 21(1):92–95PubMedCrossRefGoogle Scholar
  55. Savage C (1952) Lysergic acid diethylamide (LSD-25). A clinical-psychological study. Am J Psychiatry 108(12):896–900PubMedCrossRefGoogle Scholar
  56. Schurr J, Gitman B, Belchikov Y (2014) Controversial therapeutics: the B-adrenergic antagonist and cocaine-associated cardiovascular complications dilemma. Pharmacotherapy 34(12):1269–1281PubMedCrossRefGoogle Scholar
  57. Schwartz R, Einhorn A (1986) PCP intoxication in seven young children. Pediatr Emerg Care 2(4):238–241PubMedCrossRefGoogle Scholar
  58. Secemsky E, Lange D, Waters D, Goldschlager N, Hsue P (2011) Hemodynamic and arrhythmogenic effects of cocaine in hypertensive individuals. J Clin Hypertens 13(10):744–749CrossRefGoogle Scholar
  59. Seifert S, Schaechter J, Hershorin E, Lipshultz S (2011) Health effects of energy drinks on children, adolescents, and young adults. Pediatrics 127(3):511–528PubMedPubMedCentralCrossRefGoogle Scholar
  60. Shannon M, Lacouture P, Roa J, Woolf A (1989) Cocaine exposure among children seen at a pediatric hospital. Pediatrics 83(3):337–342PubMedGoogle Scholar
  61. Svatikova A, Covassin N, Somers K, Soucek F, Kara T, Bukartyk J (2015) A randomized trial of cardiovascular responses to energy drink consumption in healthy adults. JAMA 314(19):2079–2080PubMedCrossRefGoogle Scholar
  62. van Rijswijk C, Kneyber M, Plotz F (2006) Accidental ecstasy intoxication in an 8-month old infant. Intensive Care Med 32(4):632–633PubMedCrossRefGoogle Scholar
  63. Vernacchio L, Kelly J, Kaufmann DA (2008) Cough and cold medications use by US children, 1999–2006: results from the Sloane survey. Pediatrics 122:e323–e329PubMedCrossRefGoogle Scholar
  64. Vernacchio L, Kelly J, Kaufman D, Mitchell A (2009) Medication use among children <12 years of age in the United States: results from the slone survey. Pediatrics 124(2):446–454PubMedCrossRefGoogle Scholar
  65. Vollenweider FX, Gamma A, Liechti M, Huber T (1998) Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naive healthy volunteers. Neuropsychopharmacology 19(4):241–251PubMedCrossRefGoogle Scholar
  66. Welch M, Correa G (1980) PCP intoxication in young children and infants. Clin Pediatr 19(8):510–514CrossRefGoogle Scholar
  67. Welch W, Yang W, Taylor-Zapata P, Flynn J (2012) Antihypertensive drug use by children: are the drugs labeled and indicated? J Clin Hypertens 14(6):388–395CrossRefGoogle Scholar
  68. Widemann B, Kim A, Fox E, Baruchel S, Adamson P, Ingle A et al (2012) A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a children’s oncology group phase 1 consortium report. Clin Cancer Res 18(21):6011–6022PubMedPubMedCentralCrossRefGoogle Scholar
  69. Zielmann S, Kazmaier S, Schnull S, Wayland A (1997) S-(+)-Ketamine and circulation. Der Anaesthesist 46(Suppl 1):S43–S46PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Pediatric Nephrology, Children’s Mercy HospitalUniversity of Missouri – Kansas CityKansas CityUSA

Section editors and affiliations

  • Joseph T. Flynn
    • 1
    • 2
  1. 1.Division of NephrologySeattle Children’s HospitalSeattleUSA
  2. 2.Department of PediatricsUniversity of Washington School of MedicineSeattleUSA

Personalised recommendations