1. Pharmacologic Management of Hypertension
Deborah E. Westbrook, RPh, M.S.
Pediatric Clinical Pharmacy Specialist
Vidant Medical Center

2. Objectives
Review the pharmacologic classes of medications which are most commonly used to manage hypertension in the pediatric patient
Recognize compelling indications or patient characteristics which may influence prescribing decisions
Know the most common adverse drug reactions associated with each class of medication and how to monitor for these events
Discuss the step-wise approach to initiating drug therapy and how to alter drug regimens based on response.

3. Blood Pressure Cardiac Output Peripheral Resistance Myocardial
Contractility
Stroke Volume
Cardiac
Output
Size of vascular
compartment
Blood Pressure
Heart Rate
Peripheral
Resistance

5. ABC’s of Antihypertensive Therapy
Angiotensin Converting Enzyme (ACE) Inhibitors
Angiotensin Receptor Blockers (ARBs)
Beta-Adrenergic Antagonists
Calcium Channel Blockers
Diuretics

6. ACE Inhibitors Mechanism of Action Examples of Agents in Class
Inhibits angiotensin I from being converted to angiotensin II by blocking the angiotensin converting enzyme (ACE)
Examples of Agents in Class
Captopril
Enalapril
Lisinopril

7. ACE Inhibitors

8. ACE Inhibitors Effect on Blood Pressure Vasodilation
Prevents aldosterone release
Decreases vasopressin release
Blocks the CNS release of norepineprhine
Prevents breakdown of bradykinin
↓ PVR
↓CO
↓CO
↓CO
↓PVR

9. ACE Inhibitors Side Effects Decreased Renal Function Hyperkalemia
Cough
Angioedema
Leucopenia
Anemia

10. ACE Inhibitors Contraindications Bilateral renal artery stenosis
Solitary kidney with renal stenosis
Pregnancy

11. ACE Inhibitors Compelling Indications
Protein wasting nephropathy (Nephrotic syndrome, FSGS)
Polycystic Kidney Disease
Diabetes
Congestive Heart Failure

12. Angiotensin Receptor Antagonist (ARBs)
Mechanism of Action
Block AT1 receptors that are stimulated by Angiotensin II
Effect on Blood Pressure -Same as ACEi
Commonly Prescribed Agents in Class
Losartan
Valsartan
Irbesartan

13. Angiotensin Receptor Antagonists
Adrenals
Blood Vessels
Heart
Kidney
Pituitary
CNS

14. ARBs Side Effects Contraindications Hyperkalemia
Decreased renal function
Cough (not as common as with ACEi)
Angioedema
Contraindications
Pregnancy

15. βeta-adrenergic Antagonist
Mechanism of Action
Block the action of catecholamines on βeta-adrenergic receptors
Effect on Blood Pressure
1) Decrease heart rate and contractility
2) Decrease renin production
3) Decrease norepinephrine outflow from CNS
↓CO
↓PVR
↓CO

16. βeta-Blockers β-1 Selective Blocking Agents
Metoprolol
Atenolol
Bisoprolol
Non-selective Beta-blocker (block β1 and β2)
Propranolol
Nadolol
Non-selective Beta-blockers with α-1 antagonist action
Labetalol
Carvedilol

17. βeta- Blockers Side Effects Bronchospasm Bradycardia Fatigue
Nightmares
Requires Weaning
Masks signs and symptoms of hypoglycemia
Depression

18. βeta- Blockers Compelling Indications Use with Caution
Patients with signs of increased sympathetic drive
Pheochromocytoma
Use with Caution
Athletes
Asthmatics
Diabetics

19. Calcium Channel Blockers
Mechanism of Action
Block the influx of calcium into the vasculature and heart muscle
Effect on Blood Pressure
Vasodilation
Decreases contractility
↓PVR
↓CO

20. ø NA KK
Ca++ K K+
Na+
Calcium Channel Blockers Ø

21. Calcium Channel Blockers
Dihydropyridine Calcium Channel Blockers
Amlodipine
Nifedipine
Nicardapine
Non-dihydropyridine Calcium Channel Blockers
Diltiazem
Verapamil

22. Calcium Channel Blockers
Side Effects
Peripheral Edema
Flushing
Headache
Dizziness
Reflex tachycardia (Nifedipine)
Gingival hypertrophy

23. Calcium Channel Blockers
Compelling Indications
Renal transplant patients
Chronic lung disease
Hyperlipidemia
Black hypertensive population
Protein loosing nephropathies in patients with contraindications to ACEi/ARBs

24. Diuretics Mechanism of Action Effect on Blood Pressure
Increase water and sodium loss in renal tubule
Effect on Blood Pressure
Decreases blood volume (short term)
Decreases stiffness of blood vessels (long term)
↓CO
↓PVR

25. Diuretics Thiazides Loop Diuretics Potassium Sparing Diuretics
act at distal convoluted tubule
Loop Diuretics
act at ascending Loop of Henle
Potassium Sparing Diuretics
act in distal tubule to block aldosterone effects

27. Diuretics Side Effects Thiazides Loop Diuretics Aldosterone Inhibitors
Hypokalemia
Hyperuricemia
Hyperglycemia
Hyperlipidemia
Loop Diuretics
Hypocalcemia
Aldosterone Inhibitors
Gynecomastia
Menstrual irregularity

28. Diuretics Indications Caution/Contraindications
Often used in combination with other agents
Hypertension resulting from fluid overload
Patients on steroid therapy
Glomerulonephritis
Caution/Contraindications
Thiazides contraindicated with GFR < 30
Monitor potassium- may be low with Thiazides and Loops. May be elevated with Potassium sparing.
Athletes

29. Central α2-Agonist (Clonidine)
Mechanism of Action
Block sympathetic outflow of norepinephrine through stimulation of α-2 receptors in brain resulting in sympathetic tone reduction
Effect on Blood Pressure
Decrease Heart Rate and Contractility
Decrease Renin Release
Commonly used for attention deficit/hyperactivity disorder
↓CO
↓PVR

30. Central α2-Agonist (Clonidine)
Side Effects
Lethargy
Rebound Hypertension
Formulations
Tablets
Compounded suspension
Transdermal Patches

31. Indications for Medication
Prehypertension
90-95TH Percentile for height and age
Institute life style changes
NO medications unless compelling indications such as CKD, Diabetes, Heart Failure, or Left Ventricular Hypertrophy
Recheck in 6 months

32. Indications for Medication
Stage 1 Hypertension
95th-99th Percentile plus 5 mmHg for height and age
Lifestyle changes
Recheck in 1-2 weeks or sooner if symptomatic
Initiate therapy based on clinical or compelling indications
Patient with stage 1 hyper again need to recheck , make lifestyle changes and may elect to start therapy based on clinical presentation or compelling indication
Again if symptomatic or has compelling idictionas

33. Indications for Medication
Stage 2
>99th percentile plus 5 mmHg for age and height
Lifestyle changes
See within a week, or refer
Initiate stepwise therapy

34. What Agent to Use? Is there an identifiable cause for hypertension?
If no identifiable cause are there other co-morbidities that may be improved or worsened by the drug choice prescribed?
First line agents for consideration according to Fourth Report - CCB, ACE inhibitor, diuretics

36. Treatment Adherence Lifestyle Changes
Medication Adherence Assessment/Improvement
Parental/Patient Education
Medication Calendars
Pill Boxes
Blood pressure logs
Reminder Apps on Phone
Simplify Medication Regimen

37. References
Feld LG, Corey H. Hypertension in childhood. Pediatr Rev 2007;28;
The Fourth Report on the Diagnosis, Evaluation,and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics 2004;14:
Lande M,Flynn J. Treatment of hypertension in children and adolescents. Pediatr Nephrol 2009; 24:
Lurbe E, Cifkova R,Cruickshank JK, et al. Management of high blood pressure in children and adolescents:recommendations of the European Society of Hypertension. J Hypertens 2009; 27:
Hadtstein C,Schafer F. Hypertension in children with chronic kidney disease:pathophysiology and management. Pediatr Nephrol. 2008; 23:
James PA, Oparil S, Carter BL, et al Evidence-based guidelines for the management of high blood pressure in adults. Report from the panel members appointed too the Eighth Joint National Committee. JAMA published online December 18,2013.