Treatment of Hypertension in Pediatrics

1. Treatment of Hypertension in Pediatrics Kelsey R. Green, Pharm.D. Pediatric Clinical Pharmacist LSU-HSC in Shreveport, LA

2. Objectives • Define hypertension in children • Identify when blood pressure should be taken • Practice determining BP percentile and interpreting how to use this information to best treat the patient • Discuss treatment options used in pediatrics to treat hypertension

3. Definitions2 • Hypertension: average SBP and/or DBP >95th percentile for gender, age, and height on > 3 occasions • Prehypertension: average SBP or DBP >90th percentile but <the 95th percentile • Adolescents with BP levels >120/80 mm Hg should be considered prehypertensive

4. Measurement of Blood Pressure2 • Children >3 years old should have their BP measured when seen in a medical setting • Preferred method: Auscultation • Requires a cuff that is appropriate for the child’s arm • Right arm preferred

5. Blood Pressure Cuff2 • Equipment needed to measure BP in children (3-adolescents): • Child cuffs of different sizes • Standard adult cuff • Large adult cuff • Thigh cuff

6. Measurement of BP in children < 3 years old2 • History of prematurity, VLBW, or other neonatal complications • Congenital heart disease • Recurrent UTI, hematuria, or proteinuria • Known renal disease or urologic malformations • Family history of congenital renal disease • Solid-organ transplant • Malignancy or bone marrow transplant • Treatment with drugs known to raise BP • Systemic illnesses associated with hypertension • Evidence of elevated ICP (intracranial pressure)

7. Using the Blood Pressure Tables2 • Use the standard height charts to determine the height percentile. • Measure and record the child’s SBP and DBP. • Use the correct gender table for SBP and DBP. • Find the child’s age on the left side of the table. Follow the age row across the table to the intersection of the line for the height percentile. • Find the 50th, 90th, 95th, and 99th percentiles for SBP in the left columns and for DBP in the right columns.

8. Let’s Practice • AMF is a 5 yo female weighing 25 kg in the 75th percentile of height. Her BP is taken when she goes to the Dr. for a routine visit. Her BP is 114/73. • What is her BP percentile? • What do we do with this information?

9. What does this percentile mean?2

10. Classification of Hypertension & Therapy Recommendations2

11. Management Algorithm2

12. Diagnostic Work-Up6

13. Possible Etiologies Causing Hypertension2 • Chronic Renal Failure • Cushing Syndrome • Turner Syndrome • Hyperthyroidism • Systemic Lupus • Coarctation of the aorta • Wilms tumor

14. Treatment Strategies • Therapeutic lifestyle changes • Drug therapy

15. Lifestyle changes • Weight reduction • Regular physical activity • Restriction of sedentary activity • Dietary modification • Family-based intervention

16. Indications for Antihypertensive Drug Therapy2 • Symptomatic hypertension • Secondary hypertension • Hypertensive target-organ damage • Diabetes (types 1 and 2) • Persistent hypertension despite nonpharmacologic measures

17. Step-wise Approach to Therapy2 • Start with a small dose of a single anti-hypertensive drug • Increase dose of single anti-hypertensive drug (to max dose if tolerated) • Add a small dose of a second drug • Increase dose of second anti-hypertensive medication

18. Antihypertensive Medication • Angiotensin Converting Enzyme-Inhibitors • Angiotensin Receptor Blockers • Calcium Channel Blockers • Diuretics • Beta-Blockers • Central alpha-agonists • Peripheral alpha-antagonist • Vasodilators

19. Drug Options for Initial Therapy1

20. ACE-I1-3, 5 • Angiotensin Converting Enzyme Inhibitors • Benazepril*, Captopril, Enalapril*, Fosinopril*, Lisinopril*, Quinapril • Mechanism of Action: prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion

21. ACE-I www.medscape.com

22. ACE-I • Patient’s Characteristics: • High plasma renin activity • Renal insufficiency (unilateral renovascular hypertension, renal parenchymal disease, renal proteinuria) • Congestive heart failure • Diabetes • Hyperlipidemia

23. ACE-I • Comments: • Contraindicated in pregnancy • Monitor serum potassium and SCr • Cough and angioedema • May require a dosing adjustment in renal impairment • Fosinopril in children >50 kg • Good data on compounding Captopril into a suspension

24. ARB1-3, 5 • Angiotensin Receptor Blockers • Irbesartan*, Losartan* • Mechanism of Action: angiotensin II receptor antagonist; blocks the vasoconstrictor and aldosterone-secreting effects of anigotensin II

25. ARB www.medscape.com

26. ARB • Patient’s Characteristics: same as ACE-I • Comments: • Less studied than ACE-I • Dosing not available in Neofax or Pediatric Dosing Handbook • All are contraindicated in pregnancy • Check serum potassium and SCr • Not available currently on formulary

27. CCB1-3, 5 • Calcium Channel Blocker • Amlodipine*, Felodipine,Isradipine,Extended-release Nifedipine • Mechanism of Action:inhibits calcium ions from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization; produces a relaxation of coronary vascular smooth muscle and coronary vasodilation

28. CCB http://calcium.ion.ucl.ac.uk/images/contraction-smc.gif

29. CCB • Patient’s Characteristics: • Emergency hypertension (nifedipine) • Black race • Diabetes • Chronic obstructive lung disease • Broncho-pulmonary dysplasia • Gout • Hyperlipidemia • Peripheral Vascular Disease • Renal Transplant (cyclosporine-induced)

30. CCB • Comments: • ADR: edema, arrhythmias, headache, fatigue, dizziness, flushing • No adjustment in renal impairment • May need adjustment in hepatic impairment • Good data for compounding Amlodipine oral suspension

31. Diuretics1-3, 5 • Amiloride, Chlorothiazide, Chlorthalidone, Triamterene, Furosemide, HCTZ*, Spironolactone, Metolazone, Bumetanide • Mechanisms of Action: • Loop Diuretic: (Furosemide, Bumetanide) Inhibits reabsorption of Na and Cl in the ascending loop of Henle and distal tubule – causing increased excretion of water, K, Na, Cl, Mg, & Ca

32. Diuretics • Mechanism of Action: continued • Thiazide Diuretic: (HCTZ, Chlorothiazide) Inhibits Na reabsorption in the distal tubules causing increased excretion of Na and water as well as K, Mg, Ca, hydrogen, phosphate, & bicarb ions • K Sparing Diuretic: (Spironolactone) Competes with aldosterone for receptor sites in the distal renal tubules, increasing NaCl and water excretion while conserving K and hydrogen ions; may block the effect of aldosterone on arteriolar smooth muscle as well • Miscellaneous: (Metolazone) Inhibits sodium reabsorption in the cortical diluting site and proximal convoluted tubules

33. Diuretics http://sprojects.mmi.mcgill.ca/nephrology/presentation/images/86no2.gif

34. Diuretics • Patient’s Characteristics: • Volume dependent, low plasma renin activity • Black race • Congestive heart failure • Avoid in athletes

35. Diuretics • Comments: • ADR: Dizziness, Photosensitivity, Rash, Vomiting • Monitor Electrolytes • Adjust in renal impairment • Furosemide and Chlorothiazide available in solutions • Good data to compound Spironolactone, Metolazone and HCTZ into oral suspensions

36. BB 1-3, 5 • Βeta-Blocker • Atenolol, Bisoprolol/HCTZ,Metoprolol,Propranolol* • Mechanism of Action: Selective inhibitor of beta1-adrenergic receptors at lower doses; also inhibits beta2-receptors at higher doses

37. BB http://www.eaa-knowledge.com/ojni/ni/602/strate1.jpg

38. BB • Patient’s Characteristics: • High plasma renin activity • Hyperdynamic circulation • Anxiety • Migraine • Hyperthyroidism • Neuroadrenergic tumors

39. BB • Comments: • Good data to compound Metoprolol and Atenolol • Propranolol available as a solution • Worried about higher doses in asthma patients • Contraindicated in sick sinus syndrome • Avoid in athletes and people with diabetes

40. Goals of Therapy2

41. Long-Term Management3 • Monitor therapy for efficacy and for potential adverse effects • Measure blood pressure every 2-4 weeks until good control • Once controlled, monitor every 3-4 months

42. Step-Down Therapy2 • After blood pressure is stable, gradually reduce medication • Goal: Discontinue medication • Best Candidates: Children with uncomplicated HTN due to obesity • Continue to follow BP and continue lifestyle changes

43. Our Patient • AMF – BP was in 95th percentile • Repeated BP at 3 office visits (93rd percentile) • Recommend Lifestyle Changes • Repeat BP in 6 months (95th percentile) • Patient work-up – unilateral renovascular hypertension • Start an ACE-I

44. Conclusions • Use patient’s BP Percentile to determine if they have hypertension. • First-line agents to treat hypertension are ACE-I/ARB or CCB. • Diuretics are usually used as second line therapy.

45. References 1. Seikaly, Mouin G. Hypertension in children: an update on treatment strategies. Curr Opin Pediatr 2007; 19:170-177. 2. 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; 114:555-576. 3. Flynn, JT. Pharmacologic Treatment of Hypertension in Children and Adolescents. J Pediatr 2006; 149:746-54. 4. McNiece, Karen and Portman R. Ambulatory blood pressure monitoring: what a pediatrician should know. Curr Opin Rediatr 19:178-182. 5. Pediatric Dosage Handbook, 14th ed. Hudson, OH: Lexi-Com, 2005. 6. Luma, GB and Spiotta, RT. Hypertension in Children and Adolescents. AAFP 2006; 73: 1158-68.

46. Questions