Antihypertensives

1. Antihypertensive AgentsAntihypertensive Agents

2. HypertensionHypertension
High blood pressureHigh blood pressure
•Normal:Normal:Systolic < 130 mmSystolic < 130 mm
Hg Diastolic < 85 mm HgHg Diastolic < 85 mm Hg

3. 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
HypertensionHypertension
Stage 1Stage 1 140-159140-159 90-9990-99
Stage 2Stage 2 160-169160-169 100-109100-109
Stage 3Stage 3 180-209180-209 110-119110-119
Stage 4Stage 4 ³³ 210 210 ³³ 120 120

4. 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

5. Blood Pressure = CO x SVRBlood Pressure = CO x SVR
•CO = Cardiac outputCO = Cardiac output
•SVR = Systemic vascular resistanceSVR = Systemic vascular resistance

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

7. Antihypertensive AgentsAntihypertensive Agents
•Medications used to treat hypertensionMedications used to treat hypertension

8. 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

9. 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

10. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
Adrenergic AgentsAdrenergic Agents
Alpha1 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

11. Antihypertensive Agents: Antihypertensive Agents:
Adrenergic AgentsAdrenergic Agents
Alpha1 BlockersAlpha1 Blockers
•doxazosin (Cardura)doxazosin (Cardura)
•prazosin (Minipress)prazosin (Minipress)
•terazosin (Hytrin)terazosin (Hytrin)

12. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
Adrenergic AgentsAdrenergic Agents
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

13. Antihypertensive Agents: Antihypertensive Agents:
Adrenergic AgentsAdrenergic Agents
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)

14. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
Adrenergic AgentsAdrenergic Agents
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

15. Antihypertensive Agents: Antihypertensive Agents:
Adrenergic AgentsAdrenergic Agents
Adrenergic Neuronal BlockersAdrenergic Neuronal Blockers
(peripherally acting)(peripherally acting)
•reserpinereserpine
•guanadrel (Hylorel)guanadrel (Hylorel)
•guanethidine (Ismelin)guanethidine (Ismelin)

16. 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

17. Antihypertensive Agents: Antihypertensive Agents:
Adrenergic AgentsAdrenergic Agents
Therapeutic 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

18. 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

19. Antihypertensive Agents: Antihypertensive Agents:
Adrenergic AgentsAdrenergic Agents
Side EffectsSide Effects
Most common:Most common: dry mouthdry mouth drowsinessdrowsiness
sedationsedation constipationconstipation
Other:Other: headachesheadaches sleep disturbancessleep disturbances
nauseanausea rashrash
cardiac disturbances (palpitations)cardiac disturbances (palpitations)
HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSIONHIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

20. 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

21. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
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

22. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
ACE InhibitorsACE Inhibitors
•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

23. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
ACE InhibitorsACE Inhibitors
•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

24. Antihypertensive AgentsAntihypertensive Agents
ACE 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

25. Antihypertensive Agents: Antihypertensive Agents:
Therapeutic UsesTherapeutic Uses
ACE InhibitorsACE Inhibitors
•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

26. 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!!

27. Antihypertensive Agents: Antihypertensive Agents:
CategoriesCategories
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

28. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
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

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

30. Antihypertensive Agents: Antihypertensive Agents:
Therapeutic UsesTherapeutic Uses
Angiotensin II Receptor BlockersAngiotensin II Receptor Blockers
•HypertensionHypertension
•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

31. Antihypertensive Agents: Antihypertensive Agents:
Side EffectsSide Effects
Angiotensin II Receptor BlockersAngiotensin II Receptor Blockers
•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

32. Antihypertensive Agents: Antihypertensive Agents:
CategoriesCategories
Calcium Channel BlockersCalcium Channel Blockers
•BenzothiazepinesBenzothiazepines
•DihydropyridinesDihydropyridines
•PhenylalkylaminesPhenylalkylamines

33. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
Calcium Channel BlockersCalcium Channel Blockers
•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

34. Antihypertensive Agents Antihypertensive Agents
Calcium Channel BlockersCalcium Channel Blockers
•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)

35. Antihypertensive Agents: Antihypertensive Agents:
Therapeutic UsesTherapeutic Uses
Calcium Channel BlockersCalcium Channel Blockers
•AnginaAngina
•HypertensionHypertension
•DysrhythmiasDysrhythmias
•Migraine headachesMigraine headaches

36. Antihypertensive Agents: Antihypertensive Agents:
Side EffectsSide Effects
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

37. Antihypertensive Agents: DiureticsAntihypertensive Agents: Diuretics
•Decrease the plasma and extracellular fluid volumesDecrease the plasma and extracellular fluid volumes
•Results:Results: decreased preloaddecreased preload
decreased cardiac outputdecreased cardiac output
decreased total peripheral resistancedecreased total peripheral resistance
•Overall effect:Overall effect:decreased workload of the heart, decreased workload of the heart,
and decreased blood pressureand decreased blood pressure

38. Antihypertensive Agents: Antihypertensive Agents:
Mechanism of ActionMechanism of Action
VasodilatorsVasodilators
•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

39. Antihypertensive AgentsAntihypertensive Agents
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)

40. Antihypertensive Agents: Antihypertensive Agents:
Therapeutic UsesTherapeutic Uses
VasodilatorsVasodilators
•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

41. Antihypertensive Agents: Side Antihypertensive Agents: Side
EffectsEffects
VasodilatorsVasodilators
•Hydralazine:Hydralazine:
–dizziness, headache, anxiety, tachycardia, dizziness, headache, anxiety, tachycardia,
nausea and vomiting, diarrhea, anemia, nausea and vomiting, diarrhea, anemia,
dyspnea, edema, nasal congestiondyspnea, edema, nasal congestion
•Sodium nitroprusside:Sodium nitroprusside:
–bradycardia, hypotension, possible bradycardia, hypotension, possible
cyanide toxicitycyanide toxicity

42. 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.

43. 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.

44. 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.

45. 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 Patients should avoid smoking and eating foods
high in sodium.high in sodium.
•Encourage supervised exercise.Encourage supervised exercise.

46. 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.

47. 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.

48. 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, ingestion may aggravate low blood pressure,
leading to fainting and injury. Patients should leading 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.

49. 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