Antihypertensive Agents

Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

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

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Classification of Blood Pressure

Category
Normal High normal

Systemic BP (mm Hg)

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

Diastolic BP (mm Hg)

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

Hypertension Stage 1 Stage 2 Stage 3 Stage 4

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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
Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

Blood Pressure = CO x SVR

CO = Cardiac output
SVR = Systemic vascular resistance

Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

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

Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

Antihypertensive Agents
Medications used to treat hypertension

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Antihypertensive Agents: Categories

Adrenergic agents
Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Calcium channel blockers Diuretics Vasodilators
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Antihypertensive Agents: Categories

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

Peripheral-acting adrenergic agents

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

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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

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

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

guanethidine (Ismelin)

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Antihypertensive Agents: Adrenergic Agents

Therapeutic Uses
Alpha1 blockers (peripherally acting) Treatment of hypertension Relief of symptoms of BPH Management of of severe CHF when used with cardiac glycosides and diuretics

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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 nicotinedependent persons
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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

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Antihypertensive Agents: Adrenergic Agents

Side Effects
Most common: dry mouth sedation drowsiness constipation

Other:

headaches sleep disturbances nausea rash cardiac disturbances (palpitations)

HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

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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

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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
Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

Antihypertensive Agents: Mechanism of Action

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

Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

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

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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
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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
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Antihypertensive Agents: Side Effects

ACE Inhibitors
Fatigue Headache Dizziness Mood changes

Impaired taste
Dry, nonproductive cough, reverses when therapy is stopped

NOTE: first-dose hypotensive effect may occur!!

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Antihypertensive Agents: Categories

Angiotensin II Receptor Blockers (A II Blockers or ARBs)
Newer class

Well-tolerated
Do not cause coughing

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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

Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.

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

candesartan (Atacand)
telmisartan (Micardis)
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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

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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

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Antihypertensive Agents: Categories

Calcium Channel Blockers
Benzothiazepines Dihydropyridines Phenylalkylamines

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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

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

Phenylalkamines:
verapamil (Calan, Isoptin)

Dihydropyridines:
amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) nifedipine (Procardia), nimodipine (Nimotop)
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Antihypertensive Agents: Therapeutic Uses

Calcium Channel Blockers
Angina Hypertension Dysrhythmias Migraine headaches

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Antihypertensive Agents: Side Effects

Calcium Channel Blockers
Cardiovascular hypotension, palpitations, tachycardia Gastrointestinal constipation, nausea Other rash, flushing, peripheral edema, dermatitis
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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

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Antihypertensive Agents: Mechanism of Action

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

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

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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

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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
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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.
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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.

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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.

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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.

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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.

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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.

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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.

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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

Copyright 2002, 1998, Elsevier Science (USA). All rights reserved.