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Pharmacologic Management of
Hypertension
Deborah E. Westbrook, RPh, M.S.
Pediatric Clinical Pharmacy Specialist
Vidant Medical Center
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.
Myocardial
Contractility
Stroke Volume
Cardiac
Output
Blood Pressure
Size of vascular
compartment
Heart Rate
Peripheral
Resistance
ABC’s of Antihypertensive Therapy
 Angiotensin Converting Enzyme (ACE)
Inhibitors
 Angiotensin Receptor Blockers (ARBs)
 Beta-Adrenergic Antagonists
 Calcium Channel Blockers
 Diuretics
ACE Inhibitors
 Mechanism of Action
 Inhibits angiotensin I from being converted to angiotensin II by
blocking the angiotensin converting enzyme (ACE)
 Examples of Agents in Class
 Captopril
 Enalapril
 Lisinopril
ACE Inhibitors
ACE Inhibitors
 Effect on Blood Pressure
 Vasodilation
↓ PVR
 Prevents aldosterone release
↓CO
 Decreases vasopressin release
↓CO
 Blocks the CNS release of norepineprhine
↓CO
 Prevents breakdown of bradykinin
↓PVR
ACE Inhibitors
 Side Effects
 Decreased Renal Function
 Hyperkalemia
 Cough
 Angioedema
 Leucopenia
 Anemia
ACE Inhibitors
 Contraindications
 Bilateral renal artery stenosis
 Solitary kidney with renal stenosis
 Pregnancy
ACE Inhibitors
 Compelling Indications
 Protein wasting nephropathy (Nephrotic syndrome, FSGS)
 Polycystic Kidney Disease
 Diabetes
 Congestive Heart Failure
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
Angiotensin Receptor Antagonists
Adrenals
Blood Vessels
Heart
Kidney
Pituitary
CNS
ARBs
 Side Effects
 Hyperkalemia
 Decreased renal function
 Cough (not as common as with ACEi)
 Angioedema
 Contraindications
 Pregnancy
βeta-adrenergic Antagonist
 Mechanism of Action
 Block the action of catecholamines on βeta-adrenergic
receptors
 Effect on Blood Pressure
↓CO
1) Decrease heart rate and contractility
2) Decrease renin production
↓PVR
3) Decrease norepinephrine outflow from CNS
↓CO
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
βeta- Blockers
 Side Effects
 Bronchospasm
 Bradycardia
 Fatigue
 Nightmares
 Requires Weaning
 Masks signs and symptoms of hypoglycemia
 Depression
βeta- Blockers
 Compelling Indications
 Patients with signs of increased sympathetic drive
 Pheochromocytoma
 Use with Caution
 Athletes
 Asthmatics
 Diabetics
Calcium Channel Blockers
 Mechanism of Action

Block the influx of calcium into the vasculature and heart
muscle
 Effect on Blood Pressure
↓PVR
 Vasodilation
 Decreases contractility
↓CO
ø
K
Ca++ KK
Na+
Calcium Channel Blockers
K+
Calcium Channel Blockers
 Dihydropyridine Calcium Channel Blockers
 Amlodipine
 Nifedipine
 Nicardapine
 Non-dihydropyridine Calcium Channel Blockers
 Diltiazem
 Verapamil
Calcium Channel Blockers
 Side Effects
 Peripheral Edema
 Flushing
 Headache
 Dizziness
 Reflex tachycardia (Nifedipine)
 Gingival hypertrophy
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
Diuretics
 Mechanism of Action
 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
Diuretics
 Thiazides
 act at distal convoluted tubule
 Loop Diuretics
 act at ascending Loop of Henle
 Potassium Sparing Diuretics
 act in distal tubule to block aldosterone effects
Diuretics
 Side Effects
 Thiazides
 Hypokalemia
 Hyperuricemia
 Hyperglycemia
 Hyperlipidemia
 Loop Diuretics
 Hypokalemia
 Hypocalcemia
 Aldosterone Inhibitors
 Gynecomastia
 Menstrual irregularity
Diuretics
 Indications
 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
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
↓CO
↓PVR
 Commonly used for attention deficit/hyperactivity disorder
Central α2-Agonist (Clonidine)
 Side Effects
 Lethargy
 Rebound Hypertension
 Formulations
 Tablets
 Compounded suspension
 Transdermal Patches
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
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
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
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
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
References
 Feld LG, Corey H. Hypertension in childhood. Pediatr Rev 2007;28;283-298.
 The Fourth Report on the Diagnosis, Evaluation,andTreatment of High Blood Pressure in
Children and Adolescents. Pediatrics 2004;14:555-576.
 Lande M,Flynn J. Treatment of hypertension in children and adolescents. Pediatr Nephrol 2009;
24:1939-1949.
•
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;
27:1719-1742.
•
Hadtstein C,Schafer F. Hypertension in children with chronic kidney disease:pathophysiology
and management. Pediatr Nephrol. 2008; 23:363-371.
•
James PA, Oparil S, Carter BL, et al. 2014 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. 2013 published online December 18,2013.