Anti hypertensives agents

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

Antihypertensive AgentsAntihypertensive Agents


HypertensionHypertension

High blood pressureHigh blood pressure

• Normal:Normal: Systolic < 130 mmSystolic < 130 mmHg Diastolic < 85 mm HgHg Diastolic < 85 mm Hg


Classification of Blood PressureClassification of Blood Pressure

CategoryCategory Systemic BP (mm Hg)Systemic BP (mm Hg) Diastolic BP (mm Hg)Diastolic BP (mm Hg)

NormalNormal <130<130 <85<85

High normalHigh normal 130-139130-139 85-8985-89

HypertensionHypertensionStage 1Stage 1 140-159140-159 90-9990-99Stage 2Stage 2 160-169160-169 100-109100-109Stage 3Stage 3 180-209180-209 110-119110-119Stage 4Stage 4 210 210 120 120


Classification of Blood PressureClassification of Blood Pressure

Primary HypertensionPrimary Hypertension

• Specific cause unknownSpecific cause unknown

• 90% of the cases90% of the cases

• Also known as essential or idiopathic hypertensionAlso known as essential or idiopathic hypertension

Secondary HypertensionSecondary Hypertension

• Cause is known (such as eclampsia of pregnancy, Cause is known (such as eclampsia of pregnancy, renal artery disease, pheochromocytoma)renal artery disease, pheochromocytoma)

• 10% of the cases10% of the cases


Blood Pressure = CO x SVRBlood Pressure = CO x SVR

• CO = Cardiac outputCO = Cardiac output

• SVR = Systemic vascular resistanceSVR = Systemic vascular resistance


Instructors may want to insert Instructors may want to insert EIC Image #69:EIC Image #69:

Blood Pressure: Normal RegulationBlood Pressure: Normal Regulation



• Medications used to treat hypertensionMedications used to treat hypertension


Antihypertensive Agents: CategoriesAntihypertensive Agents: Categories

• Adrenergic agentsAdrenergic agents

• Angiotensin-converting enzyme inhibitorsAngiotensin-converting enzyme inhibitors

• Angiotensin II receptor blockersAngiotensin II receptor blockers

• Calcium channel blockersCalcium channel blockers

• DiureticsDiuretics

• VasodilatorsVasodilators


Antihypertensive Agents: CategoriesAntihypertensive Agents: Categories

• Adrenergic AgentsAdrenergic Agents

– Alpha1 blockersAlpha1 blockers

– Beta blockers (cardioselective and nonselective)Beta blockers (cardioselective and nonselective)

– Centrally acting alpha blockersCentrally acting alpha blockers

– Combined alpha-beta blockersCombined alpha-beta blockers

– Peripheral-acting adrenergic agentsPeripheral-acting adrenergic agents


Antihypertensive Agents: Antihypertensive Agents: Mechanism of ActionMechanism of ActionAdrenergic AgentsAdrenergic AgentsAlpha1 Blockers (peripherally acting)Alpha1 Blockers (peripherally acting)• Block the alpha1-adrenergic receptorsBlock the alpha1-adrenergic receptors• The SNS is not stimulatedThe SNS is not stimulated

Result: DECREASED blood pressureResult: DECREASED blood pressure

• Stimulation of alpha1-adrenergic receptors Stimulation of alpha1-adrenergic receptors causes HYPERtensioncauses HYPERtension

• Blocking alpha1-adrenergic receptors causes Blocking alpha1-adrenergic receptors causes decreased blood pressuredecreased blood pressure


Antihypertensive Agents: Antihypertensive Agents:

Adrenergic AgentsAdrenergic Agents

Alpha1 BlockersAlpha1 Blockers

• doxazosin (Cardura)doxazosin (Cardura)

• prazosin (Minipress)prazosin (Minipress)

• terazosin (Hytrin)terazosin (Hytrin)


Antihypertensive Agents: Antihypertensive Agents: Mechanism of ActionMechanism of Action


Central-Acting AdrenergicsCentral-Acting Adrenergics

• Stimulate alpha2-adrenergic receptorsStimulate alpha2-adrenergic receptors

• Sympathetic outflow from the CNS is decreasedSympathetic outflow from the CNS is decreased

Result: decreased blood pressureResult: decreased blood pressure




Central-Acting AdrenergicsCentral-Acting Adrenergics

• clonidine (Catapres)clonidine (Catapres)

• methyldopa (Aldomet) methyldopa (Aldomet) (drug of choice for hypertension in pregnancy)(drug of choice for hypertension in pregnancy)




Adrenergic Neuronal Blockers Adrenergic Neuronal Blockers (peripherally acting)(peripherally acting)

• Inhibit release of norepinephrineInhibit release of norepinephrine

• Also deplete norepinephrine storesAlso deplete norepinephrine stores

• SNS (peripheral adrenergic nerves) is not stimulatedSNS (peripheral adrenergic nerves) is not stimulated

Result: decreased blood pressureResult: decreased blood pressure




Adrenergic Neuronal BlockersAdrenergic Neuronal Blockers(peripherally acting)(peripherally acting)

• reserpinereserpine

• guanadrel (Hylorel)guanadrel (Hylorel)

• guanethidine (Ismelin)guanethidine (Ismelin)


Antihypertensive Agents: Antihypertensive Agents: Adrenergic Agents Adrenergic Agents

Therapeutic UsesTherapeutic Uses

• Alpha1 blockers (peripherally acting)Alpha1 blockers (peripherally acting)

– Treatment of hypertensionTreatment of hypertension

– Relief of symptoms of BPHRelief of symptoms of BPH

– Management of of severe CHF when used Management of of severe CHF when used with cardiac glycosides and diureticswith cardiac glycosides and diuretics


Antihypertensive Agents: Antihypertensive Agents: Adrenergic AgentsAdrenergic AgentsTherapeutic UsesTherapeutic Uses• Central-Acting AdrenergicsCentral-Acting Adrenergics

– Treatment of hypertension, either alone or Treatment of hypertension, either alone or with other agentswith other agents

– Usually used after other agents have failed Usually used after other agents have failed due to side effectsdue to side effects

– Also may be used for treatment of severe Also may be used for treatment of severe dysmenorrhea, menopausal flushing, glaucomadysmenorrhea, menopausal flushing, glaucoma

– Clonidine is useful in the management of Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine-withdrawal symptoms in opioid- or nicotine-dependent personsdependent persons


Antihypertensive Agents: Antihypertensive Agents: Adrenergic AgentsAdrenergic Agents

Therapeutic UsesTherapeutic Uses

• Adrenergic neuronal blockers Adrenergic neuronal blockers (peripherally acting) (peripherally acting)

– Treatment of hypertension, either alone or with Treatment of hypertension, either alone or with other agentsother agents

– Seldom used because of frequent side effectsSeldom used because of frequent side effects


Antihypertensive Agents: Antihypertensive Agents: Adrenergic AgentsAdrenergic Agents

Side EffectsSide Effects

Most common:Most common: dry mouthdry mouth drowsinessdrowsinesssedationsedation constipationconstipation

Other:Other: headachesheadaches sleep disturbancessleep disturbancesnauseanausea rashrashcardiac disturbances (palpitations)cardiac disturbances (palpitations)

HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSIONHIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION


Antihypertensive Agents: Antihypertensive Agents: CategoriesCategories

Angiotensin-Converting Enzyme InhibitorsAngiotensin-Converting Enzyme Inhibitors

(ACE Inhibitors)(ACE Inhibitors)

• Large group of safe and effective drugsLarge group of safe and effective drugs

• Often used as first-line agents for CHF Often used as first-line agents for CHF and hypertensionand hypertension

• May be combined with a thiazide diuretic May be combined with a thiazide diuretic or calcium channel blockeror calcium channel blocker



ACE InhibitorsACE Inhibitors

RAAS: Renin Angiotensin-Aldosterone SystemRAAS: Renin Angiotensin-Aldosterone System

• When the enzyme angiotensin I is converted to When the enzyme angiotensin I is converted to angiotensin II, the result is potent vasoconstriction angiotensin II, the result is potent vasoconstriction and stimulation of aldosteroneand stimulation of aldosterone

• Result of vasoconstriction: increased systemic Result of vasoconstriction: increased systemic vascular resistance and increased afterload vascular resistance and increased afterload

• Therefore, increased BPTherefore, increased BP




• Aldosterone stimulates water and sodium resorption.Aldosterone stimulates water and sodium resorption.

• Result: increased blood volume, increased preload, Result: increased blood volume, increased preload, and increased Band increased B




• ACE Inhibitors block the angiotensin-converting ACE Inhibitors block the angiotensin-converting enzyme, thus preventing the formation of enzyme, thus preventing the formation of angiotensin II.angiotensin II.

• Also prevent the breakdown of the vasodilating Also prevent the breakdown of the vasodilating substance, bradykininsubstance, bradykinin

Result: decreased systemic vascular resistance (afterload), Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore, decreased blood pressurevasodilation, and therefore, decreased blood pressure


Antihypertensive AgentsAntihypertensive AgentsACE InhibitorsACE Inhibitors• captopril (Capoten)captopril (Capoten)• Short half-life, must be dosed more frequently Short half-life, must be dosed more frequently

than othersthan others• enalapril (Vasotec)enalapril (Vasotec)• The only ACE inhibitor available in oral and The only ACE inhibitor available in oral and

parenteral formsparenteral forms• lisinopril (Prinivil and Zestril) and quinapril (Accupril)lisinopril (Prinivil and Zestril) and quinapril (Accupril)• Newer agents, long half-lives, once-a-day dosingNewer agents, long half-lives, once-a-day dosing• Several other agents availableSeveral other agents available


Antihypertensive Agents: Antihypertensive Agents: Therapeutic UsesTherapeutic Uses


• HypertensionHypertension

• CHF (either alone or in combination with diuretics CHF (either alone or in combination with diuretics or other agents)or other agents)

• Slows progression of left ventricular hypertrophy Slows progression of left ventricular hypertrophy after an MIafter an MI

• Renal protective effects in patients with diabetesRenal protective effects in patients with diabetes

Drugs of choice in hypertensive patients with CHFDrugs of choice in hypertensive patients with CHF


Antihypertensive Agents: Antihypertensive Agents: Side EffectsSide Effects

ACE InhibitorsACE Inhibitors• FatigueFatigue DizzinessDizziness• HeadacheHeadache Mood changesMood changes• Impaired tasteImpaired taste

Dry, nonproductive cough, reverses when therapy is stoppedDry, nonproductive cough, reverses when therapy is stopped

NOTE: first-dose hypotensive effect may occur!!NOTE: first-dose hypotensive effect may occur!!



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

• Newer classNewer class

• Well-toleratedWell-tolerated

• Do not cause coughingDo not cause coughing



Angiotensin II Receptor BlockersAngiotensin II Receptor Blockers

• Allow angiotensin I to be converted to angiotensin II, Allow angiotensin I to be converted to angiotensin II, but block the receptors that receive angiotensin IIbut block the receptors that receive angiotensin II

• Block vasoconstriction and release of aldosteroneBlock vasoconstriction and release of aldosterone


Antihypertensive Agents:Antihypertensive Agents:


• losartan (Cozaar)losartan (Cozaar)

• eposartan (Teveten)eposartan (Teveten)

• valsartan (Diovan)valsartan (Diovan)

• irbesartan (Avapro)irbesartan (Avapro)

• candesartan (Atacand)candesartan (Atacand)

• telmisartan (Micardis)telmisartan (Micardis)





• Adjunctive agents for the treatment of CHFAdjunctive agents for the treatment of CHF

• May be used alone or with other agents such May be used alone or with other agents such as diureticsas diuretics




• Upper respiratory infectionsUpper respiratory infections

• HeadacheHeadache

• May cause occasional dizziness, inability to sleep, May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigueback pain, fatigue



Calcium Channel BlockersCalcium Channel Blockers

• BenzothiazepinesBenzothiazepines

• DihydropyridinesDihydropyridines

• PhenylalkylaminesPhenylalkylamines




• Cause smooth muscle relaxation by blocking the Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing binding of calcium to its receptors, preventing muscle contractionmuscle contraction

• This causes decreased peripheral smooth muscle This causes decreased peripheral smooth muscle tone, decreased systemic vascular resistancetone, decreased systemic vascular resistance

• Result: decreased blood pressureResult: decreased blood pressure


Antihypertensive Agents Antihypertensive Agents


• Benzothiazepines:Benzothiazepines:– diltiazem (Cardizem, Dilacor)diltiazem (Cardizem, Dilacor)

• Phenylalkamines:Phenylalkamines:– verapamil (Calan, Isoptin)verapamil (Calan, Isoptin)

• Dihydropyridines:Dihydropyridines:– amlodipine (Norvasc), bepridil (Vascor), amlodipine (Norvasc), bepridil (Vascor),

nicardipine (Cardene)nicardipine (Cardene)

– nifedipine (Procardia), nimodipine (Nimotop)nifedipine (Procardia), nimodipine (Nimotop)




• AnginaAngina


• DysrhythmiasDysrhythmias

• Migraine headachesMigraine headaches



Calcium Channel BlockersCalcium Channel Blockers• CardiovascularCardiovascular

– hypotension, palpitations, tachycardiahypotension, palpitations, tachycardia

• GastrointestinalGastrointestinal– constipation, nauseaconstipation, nausea

• OtherOther– rash, flushing, peripheral edema, dermatitisrash, flushing, peripheral edema, dermatitis


Antihypertensive Agents: DiureticsAntihypertensive Agents: Diuretics

• Decrease the plasma and extracellular fluid volumesDecrease the plasma and extracellular fluid volumes

• Results:Results: decreased preloaddecreased preloaddecreased cardiac outputdecreased cardiac outputdecreased total peripheral decreased total peripheral

resistanceresistance

• Overall effect:Overall effect: decreased workload of the heart, decreased workload of the heart, and decreased blood pressureand decreased blood pressure


Antihypertensive Agents: Antihypertensive Agents: Mechanism of ActionMechanism of ActionVasodilatorsVasodilators

• Directly relaxes arteriolar smooth muscleDirectly relaxes arteriolar smooth muscle

• Result:Result: decreased systemic vascular response, decreased systemic vascular response,

decreased afterload, anddecreased afterload, and

PERIPHERAL VASODILATIONPERIPHERAL VASODILATION



VasodilatorsVasodilators

• diazoxide (Hyperstat)diazoxide (Hyperstat)

• hydralazine HCl (Apresoline)hydralazine HCl (Apresoline)

• minoxidil (Loniten, Rogaine)minoxidil (Loniten, Rogaine)

• sodium nitroprusside (Nipride, Nitropress)sodium nitroprusside (Nipride, Nitropress)




• Treatment of hypertensionTreatment of hypertension

• May be used in combination with other agentsMay be used in combination with other agents

• Sodium nitroprusside and diazoxide IV are reserved Sodium nitroprusside and diazoxide IV are reserved for the management of hypertensive emergenciesfor the management of hypertensive emergencies


Antihypertensive Agents: Side Antihypertensive Agents: Side EffectsEffects


• Hydralazine:Hydralazine:

– dizziness, headache, anxiety, tachycardia, nausea dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestiondyspnea, edema, nasal congestion

• Sodium nitroprusside:Sodium nitroprusside:

– bradycardia, hypotension, possible bradycardia, hypotension, possible cyanide toxicitycyanide toxicity


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications

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

• Assess for contraindications to specific Assess for contraindications to specific antihypertensive agents.antihypertensive agents.

• Assess for conditions that require cautious Assess for conditions that require cautious use of these agents.use of these agents.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Educate patients about the importance of not Educate patients about the importance of not

missing a dose and taking the medications exactly missing a dose and taking the medications exactly as prescribed.as prescribed.

• Patients should never double up on doses if a dose Patients should never double up on doses if a dose is missed; check with physician for instructions on is missed; check with physician for instructions on what to do if a dose is missed.what to do if a dose is missed.

• Monitor BP during therapy. Instruct patients to Monitor BP during therapy. Instruct patients to keep a journal of regular BP checks.keep a journal of regular BP checks.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Instruct patients that these drugs should not be Instruct patients that these drugs should not be

stopped abruptly, as this may cause a rebound stopped abruptly, as this may cause a rebound hypertensive crisis, and perhaps lead to CVA.hypertensive crisis, and perhaps lead to CVA.

• Oral forms should be given with meals so that Oral forms should be given with meals so that absorption is more gradual and effective.absorption is more gradual and effective.

• Administer IV forms with extreme caution and Administer IV forms with extreme caution and use an IV pump.use an IV pump.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Remind patients that medications is only part of Remind patients that medications is only part of

therapy. Encourage patients to watch their diet, therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake.stress level, weight, and alcohol intake.

• Patients should avoid smoking and eating foods high Patients should avoid smoking and eating foods high in sodium.in sodium.

• Encourage supervised exercise.Encourage supervised exercise.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Instruct patients to change positions slowly to avoid Instruct patients to change positions slowly to avoid

syncope from postural hypotension.syncope from postural hypotension.

• Patients should report unusual shortness of breath; Patients should report unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; or around the eyes; weight gain or loss; chest pain; palpitations; or excessive fatigue.palpitations; or excessive fatigue.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Men taking these agents may not be aware that Men taking these agents may not be aware that

impotence is an expected effect. This may influence impotence is an expected effect. This may influence compliance with drug therapy.compliance with drug therapy.

• If patients are experiencing serious side effects, If patients are experiencing serious side effects, or believe that the dose or medication needs to or believe that the dose or medication needs to be changed, they should contact their physician be changed, they should contact their physician immediately.immediately.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Hot tubs, showers, or baths; hot weather; prolonged Hot tubs, showers, or baths; hot weather; prolonged

sitting or standing; physical exercise; and alcohol sitting or standing; physical exercise; and alcohol ingestion may aggravate low blood pressure, leading ingestion may aggravate low blood pressure, leading to fainting and injury. Patients should to fainting and injury. Patients should sit or lie down until symptoms subside.sit or lie down until symptoms subside.

• Patients should not take any other medications, Patients should not take any other medications, including OTC drugs, without first getting the including OTC drugs, without first getting the approval of their physician.approval of their physician.


Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Monitor for side/adverse effects Monitor for side/adverse effects

(dizziness, orthostatic hypotension, fatigue) (dizziness, orthostatic hypotension, fatigue) and for toxic effects.and for toxic effects.

• Monitor for therapeutic effectsMonitor for therapeutic effects

• Blood pressure should be maintained at less Blood pressure should be maintained at less than 140/90 mm Hgthan 140/90 mm Hg

Education

Anti hypertensives agents