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Treatment of Hypertension in Pediatrics

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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 -Elevated BP must be confirmed on repeated visits. -Ideally, the child should have avoided stimulant drugs or foods, have been sitting quietly for 5 minutes, and seated with his or her back supported, feet on the floor and right arm supported at heart level.

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? BP percentile – 95th

9 What does this percentile mean?2
Normal <90th Prehypertension 90-<95th or if >120-80 Stage 1 hypertension 95th-99th plus 5 mm Hg Stage 2 hypertension >99th plus 5 mm Hg > Than 95th percentile should be staged. If stage 1 (95-99th). BP should be repeated on 2 more occasions. If hypertension is confirmed – proceed with evaluation. If stage 2 (>99th) prompt referral – if symptomatic – immediate referral.

10 Classification of Hypertension & Therapy Recommendations2
Normal Encourage healthy diet, sleep, & physical activity Prehypertension Physical activity & diet management; No medication unless compelling indications such as chronic kidney disease, DM, HF or LVH exist Stage 1 Hypertension Physical activity & diet management; Initiate therapy Stage 2 Hypertension Physical activity & diet management; Initiate therapy (more than 1 drug may be required) -Prehypertension – start medication within months if indicated -Stage 1 hypertension – start medication within 1 month of diagnosis -Stage 2 hypertension – start medication within 1 week or immediately if symptomatic

11 Management Algorithm2

12 Diagnostic Work-Up6 Urinalysis
Rule out infection, hematuria, proteinuria Protein/Cr Ratio Kidney function Renal Ultrasound Rule out renal scarring, congenital renal anomalies EKG Cardiomegaly CBC with differential Rule out anemia, consistent with chronic renal disease Electrolyetes, BUN, Cr Rule out renal disease, pyelonephritis

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
Class of Drugs Patients’ Characteristics ACE-Is/ARBs First-line therapy CCBs Diuretics Adjunct second-line drug β–Blocker Avoid in athletes (controversial) and people with diabetes

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

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 CI in pregnancy – females of childbearing age should use reliable contraception The risk of angioedema is higher within the first 30 days of use, for African Americans, for lisinopril or enalapril (compared to captopril) and for patients previously hospitalized.

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 ARB – very similar to ACE-I; there main benefit is less side effects (such as cough and angioedema)

25 ARB

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 MOA: decrease intracellular calcium concentrations and results in dilation of peripheral arterioles

28 CCB

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 Mechanisms of Action:
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

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

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 Disease State
Desired Percentile for Gender, Age, & Height Uncomplicated primary HTN with no target-organ damage <95th Percentile Chronic renal disease, diabetes, hypertensive target-organ damage <90th Percentile

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: 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: 3. Flynn, JT. Pharmacologic Treatment of Hypertension in Children and Adolescents. J Pediatr 2006; 149: 4. McNiece, Karen and Portman R. Ambulatory blood pressure monitoring: what a pediatrician should know. Curr Opin Rediatr 19: 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:

46 Questions              

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