Drugs for Hypertension 1

Classification of Blood Pressure (BP) Four BP categories (defined by JNC 7): Normal Systolic BP below 120 mm Hg and diastolic BP below 80 mm Hg Prehypertension Systolic BP 120–139 mm Hg or diastolic BP 80–89 mm Hg Hypertension Systolic BP above 140 mm Hg or diastolic BP above 90 mm Hg Stage 2 hypertension: systolic BP and diastolic BP in different categories (eg, 160/92 mm Hg) 2

Types of Hypertension Two broad categories of hypertension Primary (essential) hypertension No identifiable cause Chronic, progressive disorder Population: older adults, African Americans, Mexican Americans, postmenopausal women Treated but not cured (lifelong condition) Referred to as “essential hypertension” Secondary hypertension Identifiable primary cause Possible to treat the cause directly Some individuals can actually be cured 3

Consequences of Hypertension Heart disease Myocardial infarction (MI) Heart failure Angina pectoris Kidney disease Stroke 4

Basic Considerations Benefits of lowering blood pressure Patient evaluation Hypertension with a treatable cause Factors that increase cardiovascular risk Diagnostic tests Treatment goals Therapeutic interventions 5

Lifestyle Modifications Sodium restriction DASH (Dietary Approaches to Stop Hypertension) eating plan Alcohol restriction Aerobic exercise Smoking cessation Maintenance of potassium and calcium intake 6

Pharmacologic Therapy Review of blood pressure control Principal determinants of blood pressure Arterial pressure = Cardiac output × Peripheral resistance Cardiac output Heart rate Myocardial contractility Blood volume Venous return Systems that help regulate blood pressure Sympathetic baroreceptor reflex Renin-angiotensin-aldosterone system Renal regulation of blood pressure 7

Pharmacologic Therapy Antihypertensive mechanisms: sites of drug action Brainstem Sympathetic ganglia Terminals of adrenergic nerves Beta1-adrenergic receptors on the heart Alpha1-adrenergic receptors on blood vessels Vascular smooth muscle Renal tubules Beta1 receptors on juxtaglomerular cells Angiotensin-converting enzyme Angiotensin II receptors Aldosterone receptors 8

Pharmacologic Therapy Classes of antihypertensive drugs Diuretics Thiazide diuretics High-ceiling (loop) diuretics Potassium-sparing diuretics Sympatholytics (antiadrenergic drugs) Beta-adrenergic blockers Alpha1 blockers Alpha/beta blockers: carvedilol and labetalol Centrally acting alpha1 agonists Adrenergic neuron blockers 9

Pharmacologic Therapy Sympatholytics (antiadrenergic drugs) (cont’d) Direct-acting vasodilators: hydralazine and minoxidil Calcium channel blockers Drugs that suppress RAAS ACE inhibitors Angiotensin II receptor blockers Aldosterone antagonists Direct renin inhibitors ACE = angiotensin-converting enzyme; RAAS = renin-angiotensin-aldosterone system. 10

Pharmacologic Therapy Fundamentals of hypertension drug therapy Treatment algorithm Initial drug selection Patients WITHOUT compelling indications Patients WITH compelling indications Adding drugs to the regimen Rationale for drug selection Benefits of multidrug therapy Dosing Step-down therapy 11

Pharmacologic Therapy Individualizing therapy Patients with comorbid conditions Renal disease Diabetes Patients in special populations African Americans Children and adolescents The elderly 12

Pharmacologic Therapy Minimizing adverse effects Promoting adherence Why adherence can be difficult to achieve Ways to promote adherence Educate the patient Teach self-monitoring Minimize side effects Establish a collaborative relationship Simplify the regimen Other measures 13

Drugs for Hypertensive Emergencies Sodium nitroprusside Fenoldopam Labetalol Diazoxide Clevidipine 14

Drugs for Hypertensive Disorders of Pregnancy Chronic hypertension and pregnancy ACE inhibitors, ARBs, and DRIs are contraindicated during pregnancy Most other antihypertensives can be continued during pregnancy Preeclampsia and eclampsia Hydralazine Magnesium sulfate (anticonvulsant) ARB = angiotensin receptor blocker; DRI = direct renin inhibitor. 15