Antihypertensive Agents

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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 Hypertension Stage 1 Stage 2 Stage 3 Stage 4 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

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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
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Blood Pressure = CO x SVR
• CO = Cardiac output • SVR = Systemic vascular resistance

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

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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: Other: dry mouth sedation drowsiness constipation

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
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Antihypertensive Agents: Mechanism of Action
ACE Inhibitors
• Aldosterone stimulates water and sodium resorption. • Result: increased blood volume, increased preload, and increased B

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

Dizziness Mood changes

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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

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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

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