Antihypertensive Agents

Rule of Halves
100 50

25
12.5

Target ORGAN DAMAGE

Coronary heart disease Heart failure Myocardial infarction

Stroke Cerebral hemorrhage

Left ventricular hypertrophy

Aortic aneurysm

Hypertension

Chronic kidney failure Hypertensive encephalopathy All Vascular

4

Retinopathy Peripheral vascular disease

Adapted from: Arch Intern Med 1996; 156:1926-1935.

JNC 7, where is ARB

Types of Hypertension
Primary hypertension
Secondary hypertension

Hypertension
High blood pressure
Normal: Systolic < 130 mm Diastolic < 85 mm Hg Hg

Classification of Blood Pressure

Category Systemic BP (mm Hg) Diastolic BP (mm Hg)

Normal
High normal Hypertension Stage 1 Stage 2 Stage 3 Stage 4

<130
130-139 140-159 160-169 180-209 210

<85
85-89 90-99 100-109 110-119 120

Classification of Blood Pressure

Primary Hypertension
Specific cause unknown 90% of the cases Also known as essential or idiopathic hypertension

Secondary Hypertension
Cause is known (such as eclampsia of pregnancy, renal artery disease, pheochromocytoma) 10% of the cases

Blood Pressure = CO x SVR

CO = Cardiac output SVR = Systemic vascular resistance

Instructors may want to insert EIC Image #69: Blood Pressure: Normal Regulation

Antihypertensive Agents
Medications used to treat hypertension

Antihypertensive Agents: Categories

Adrenergic agents Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Calcium channel blockers Diuretics Vasodilators

Antihypertensive Agents: Categories

Adrenergic Agents
Alpha1 blockers Beta blockers (cardioselective and nonselective) Centrally acting alpha blockers Combined alpha-beta blockers Peripheral-acting adrenergic agents

Antihypertensive Agents: Mechanism of Action

Adrenergic Agents Alpha1 Blockers (peripherally acting)
Block the alpha1-adrenergic receptors The SNS is not stimulated
Result: DECREASED blood pressure

Stimulation of alpha1-adrenergic receptors causes HYPERtension Blocking alpha1-adrenergic receptors causes decreased blood pressure

Antihypertensive Agents:
Adrenergic Agents Alpha1 Blockers
doxazosin (Cardura) prazosin (Minipress) terazosin (Hytrin)

Antihypertensive Agents: Mechanism of Action

Adrenergic Agents Central-Acting Adrenergics
Stimulate alpha2-adrenergic receptors Sympathetic outflow from the CNS is decreased

Result: decreased blood pressure

Antihypertensive Agents:
Adrenergic Agents Central-Acting Adrenergics
clonidine (Catapres) methyldopa (Aldomet) (drug of choice for hypertension in pregnancy)

Antihypertensive Agents: Mechanism of Action

Adrenergic Agents Adrenergic Neuronal Blockers (peripherally acting)
Inhibit release of norepinephrine
Also deplete norepinephrine stores SNS (peripheral adrenergic nerves) is not stimulated

Result: decreased blood pressure

Antihypertensive Agents:
Adrenergic Agents Adrenergic Neuronal Blockers (peripherally acting)
reserpine guanadrel (Hylorel) guanethidine (Ismelin)

Therapeutic Uses

Antihypertensive Agents: Adrenergic Agents

Alpha1 blockers (peripherally acting)

Treatment of hypertension Relief of symptoms of BPH Management of of severe CHF when used with cardiac glycosides and diuretics

Antihypertensive Agents: Adrenergic Agents

Therapeutic Uses
Central-Acting Adrenergics

Treatment of hypertension, either alone or with other agents

Usually used after other agents have failed due to side effects Also may be used for treatment of severe dysmenorrhea, menopausal flushing, glaucoma

Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine-

Antihypertensive Agents: Adrenergic Agents

Therapeutic Uses
Adrenergic neuronal blockers (peripherally acting)

Treatment of hypertension, either alone or with other agents Seldom used because of frequent side effects

Antihypertensive Agents: Adrenergic Agents

Side Effects
Most common:
Other:

dry mouth drowsiness sedation constipation headaches sleep disturbances nausea rash cardiac disturbances (palpitations)

HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

Antihypertensive Agents: Categories

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)
Large group of safe and effective drugs Often used as first-line agents for CHF and hypertension May be combined with a thiazide diuretic or calcium channel blocker

Antihypertensive Agents: Mechanism of Action

ACE Inhibitors
RAAS: Renin Angiotensin-Aldosterone System
When the enzyme angiotensin I is converted to angiotensin II, the result is potent vasoconstriction and stimulation of aldosterone

Result of vasoconstriction: increased systemic vascular resistance and increased afterload

Therefore, increased BP

Antihypertensive Agents: Mechanism of Action

ACE Inhibitors
Aldosterone stimulates water and sodium resorption. Result: increased blood volume, increased preload, and increased B

Antihypertensive Agents: Mechanism of Action

ACE Inhibitors
ACE Inhibitors block the angiotensin-converting enzyme, thus preventing the formation of angiotensin II. Also prevent the breakdown of the vasodilating substance, bradykinin
Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore, decreased blood pressure

Antihypertensive Agents
ACE Inhibitors
captopril (Capoten) Short half-life, must be dosed more frequently than others enalapril (Vasotec)

The only ACE inhibitor available in oral and parenteral forms

lisinopril (Prinivil and Zestril) and quinapril (Accupril)

Newer agents, long half-lives, once-a-day dosing

Several other agents available

Antihypertensive Agents: Therapeutic Uses

ACE Inhibitors
Hypertension CHF (either alone or in combination with diuretics or other agents) Slows progression of left ventricular hypertrophy after an MI Renal protective effects in patients with diabetes
Drugs of choice in hypertensive patients with CHF

Antihypertensive Agents: Side Effects

ACE Inhibitors
Fatigue Headache Impaired taste
Dry, nonproductive cough, reverses when therapy is stopped NOTE: first-dose hypotensive effect may occur!!

Dizziness Mood changes

Antihypertensive Agents: Categories

Angiotensin II Receptor Blockers Blockers or ARBs)
Newer class Well-tolerated Do not cause coughing

(A II

Antihypertensive Agents: Mechanism of Action

Angiotensin II Receptor Blockers
Allow angiotensin I to be converted to angiotensin II, but block the receptors that receive angiotensin II
Block vasoconstriction and release of aldosterone

Antihypertensive Agents:
Angiotensin II Receptor Blockers
losartan (Cozaar) eposartan (Teveten) valsartan (Diovan) irbesartan (Avapro) candesartan (Atacand) telmisartan (Micardis)

Antihypertensive Agents: Therapeutic Uses

Angiotensin II Receptor Blockers
Hypertension Adjunctive agents for the treatment of CHF May be used alone or with other agents such as diuretics

Antihypertensive Agents: Side Effects

Angiotensin II Receptor Blockers
Upper respiratory infections Headache May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue

Antihypertensive Agents: Categories

Calcium Channel Blockers
Benzothiazepines Dihydropyridines Phenylalkylamines

Antihypertensive Agents: Mechanism of Action

Calcium Channel Blockers
Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction This causes decreased peripheral smooth muscle tone, decreased systemic vascular resistance Result: decreased blood pressure

Antihypertensive Agents
Calcium Channel Blockers
Benzothiazepines:
diltiazem (Cardizem, Dilacor)

Phenylalkamines:
verapamil (Calan, Isoptin)

Dihydropyridines:
amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) nifedipine (Procardia), nimodipine (Nimotop)

Antihypertensive Agents: Therapeutic Uses

Calcium Channel Blockers
Angina Hypertension Dysrhythmias Migraine headaches

Antihypertensive Agents: Side Effects

Calcium Channel Blockers
Cardiovascular

hypotension, palpitations, tachycardia

Gastrointestinal

constipation, nausea
Other

rash, flushing, peripheral edema, dermatitis

Antihypertensive Agents: Diuretics

Decrease the plasma and extracellular fluid volumes Results: decreased preload decreased cardiac output decreased total peripheral resistance
Overall effect: decreased workload of the heart, and decreased blood pressure

Antihypertensive Agents: Mechanism of Action

Vasodilators
Directly relaxes arteriolar smooth muscle Result: decreased systemic vascular response, decreased afterload, and PERIPHERAL VASODILATION

Antihypertensive Agents
Vasodilators
diazoxide (Hyperstat) hydralazine HCl (Apresoline) minoxidil (Loniten, Rogaine) sodium nitroprusside (Nipride, Nitropress)

Antihypertensive Agents: Therapeutic Uses

Vasodilators
Treatment of hypertension May be used in combination with other agents Sodium nitroprusside and diazoxide IV are reserved for the management of hypertensive emergencies

Antihypertensive Agents: Side Effects

Vasodilators Hydralazine:
dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestion

Sodium nitroprusside:
bradycardia, hypotension, possible cyanide toxicity

Antihypertensive Agents: Nursing Implications

Before beginning therapy, obtain a thorough health history and head-to-toe physical examination.

Assess for contraindications to specific antihypertensive agents. Assess for conditions that require cautious use of these agents.

Antihypertensive Agents: Nursing Implications

Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed. Patients should never double up on doses if a dose is missed; check with physician for instructions on what to do if a dose is missed. Monitor BP during therapy. Instruct patients to keep a journal of regular BP checks.

Antihypertensive Agents: Nursing Implications

Instruct patients that these drugs should not be stopped abruptly, as this may cause a rebound hypertensive crisis, and perhaps lead to CVA. Oral forms should be given with meals so that absorption is more gradual and effective. Administer IV forms with extreme caution and use an IV pump.

Antihypertensive Agents: Nursing Implications

Remind patients that medications is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake. Patients should avoid smoking and eating foods high in sodium. Encourage supervised exercise.

Antihypertensive Agents: Nursing Implications

Instruct patients to change positions slowly to avoid syncope from postural hypotension. Patients should report unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; palpitations; or excessive fatigue.

Antihypertensive Agents: Nursing Implications

Men taking these agents may not be aware that impotence is an expected effect. This may influence compliance with drug therapy. If patients are experiencing serious side effects, or believe that the dose or medication needs to be changed, they should contact their physician immediately.

Antihypertensive Agents: Nursing Implications

Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low blood pressure, leading to fainting and injury. Patients should sit or lie down until symptoms subside. Patients should not take any other medications, including OTC drugs, without first getting the approval of their physician.

Antihypertensive Agents: Nursing Implications

Monitor for side/adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects. Monitor for therapeutic effects Blood pressure should be maintained at less than 140/90 mm Hg