Deborah E. Westbrook, RPh, M.S.Pediatric Clinical Pharmacy Specialist

Vidant Medical Center

Pharmacologic Management of Hypertension

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.

Blood Pressure

Cardiac Output

Peripheral Resistance

Stroke Volume

Heart Rate

MyocardialContractility

Size of vascularcompartment

ABC’s of Antihypertensive TherapyAngiotensin Converting Enzyme

(ACE) Inhibitors

Angiotensin Receptor Blockers (ARBs)

Beta-Adrenergic Antagonists

Calcium Channel Blockers

Diuretics

ACE InhibitorsMechanism of Action

Inhibits angiotensin I from being converted to angiotensin II by blocking the angiotensin converting enzyme (ACE)

Examples of Agents in ClassCaptoprilEnalaprilLisinopril

ACE Inhibitors

ACE InhibitorsEffect on Blood Pressure

Vasodilation Prevents aldosterone releaseDecreases vasopressin releaseBlocks the CNS release of norepineprhinePrevents breakdown of bradykinin

↓ PVR

↓CO

↓CO↓CO

↓PVR

ACE InhibitorsSide Effects

Decreased Renal Function

Hyperkalemia

Cough

Angioedema

Leucopenia

Anemia

ACE InhibitorsContraindications

Bilateral renal artery stenosis

Solitary kidney with renal stenosis

Pregnancy

ACE InhibitorsCompelling Indications

Protein wasting nephropathy (Nephrotic syndrome, FSGS)

Polycystic Kidney Disease

Diabetes

Congestive Heart Failure

Angiotensin Receptor Antagonist(ARBs)

Mechanism of ActionBlock AT1 receptors that are stimulated by

Angiotensin II

Effect on Blood Pressure -Same as ACEi

Commonly Prescribed Agents in ClassLosartanValsartanIrbesartan

Adrenals

Blood Vessels

Heart

Kidney

Pituitary

CNS

Angiotensin Receptor Antagonists

ARBsSide Effects

Hyperkalemia

Decreased renal function

Cough (not as common as with ACEi)

Angioedema

ContraindicationsPregnancy

βeta-adrenergic AntagonistMechanism of Action

Block the action of catecholamines on βeta-adrenergic receptors

Effect on Blood Pressure1) Decrease heart rate and contractility 2) Decrease renin production3) Decrease norepinephrine outflow from CNS

↓CO

↓PVR↓CO

βeta-Blockersβ-1 Selective Blocking Agents

MetoprololAtenololBisoprolol

Non-selective Beta-blocker (block β1 and β2)PropranololNadolol

Non-selective Beta-blockers with α-1 antagonist actionLabetalolCarvedilol

βeta- BlockersSide Effects

Bronchospasm

Bradycardia

Fatigue

Nightmares

Requires Weaning

Masks signs and symptoms of hypoglycemia

Depression

βeta- BlockersCompelling 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 PressureVasodilationDecreases contractility

↓PVR

↓CO

NA

KKK

Calcium Channel Blockers

Ca++

Na+K+

ø

Calcium Channel BlockersDihydropyridine Calcium Channel Blockers

AmlodipineNifedipineNicardapine

Non-dihydropyridine Calcium Channel BlockersDiltiazemVerapamil

Calcium Channel BlockersSide Effects

Peripheral Edema

Flushing

Headache

Dizziness

Reflex tachycardia (Nifedipine)

Gingival hypertrophy

Calcium Channel BlockersCompelling Indications

Renal transplant patients

Chronic lung disease

Hyperlipidemia

Black hypertensive population

Protein loosing nephropathies in patients with contraindications to ACEi/ARBs

DiureticsMechanism 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

DiureticsThiazides

act at distal convoluted tubule

Loop Diureticsact at ascending Loop of Henle

Potassium Sparing Diureticsact in distal tubule to block aldosterone

effects

DiureticsSide Effects

ThiazidesHypokalemiaHyperuricemiaHyperglycemiaHyperlipidemia

Loop DiureticsHypokalemiaHypocalcemia

Aldosterone InhibitorsGynecomastiaMenstrual irregularity

DiureticsIndications

Often used in combination with other agentsHypertension resulting from fluid overload

Patients on steroid therapyGlomerulonephritis

Caution/ContraindicationsThiazides contraindicated with GFR < 30Monitor 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 PressureDecrease Heart Rate and Contractility Decrease Renin Release

Commonly used for attention deficit/hyperactivity disorder

↓CO

↓PVR

Central α2-Agonist (Clonidine)Side Effects

LethargyRebound Hypertension

FormulationsTabletsCompounded suspensionTransdermal Patches

Indications for MedicationPrehypertension

90-95TH Percentile for height and ageInstitute life style changesNO medications unless compelling

indications such as CKD, Diabetes, Heart Failure, or Left Ventricular Hypertrophy

Recheck in 6 months

Indications for MedicationStage 1 Hypertension

95th-99th Percentile plus 5 mmHg for height and age

Lifestyle changesRecheck in 1-2 weeks or sooner if

symptomatic Initiate therapy based on clinical or

compelling indications

Indications for MedicationStage 2

>99th percentile plus 5 mmHg for age and height

Lifestyle changesSee 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 AdherenceLifestyle Changes

Medication Adherence Assessment/ImprovementParental/Patient EducationMedication CalendarsPill BoxesBlood pressure logsReminder Apps on PhoneSimplify Medication Regimen

References Feld LG, Corey H. Hypertension in childhood. Pediatr Rev 2007;28;283-

298. The Fourth Report on the Diagnosis, Evaluation,and Treatment 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.