Antihypertensive Agents

Antihypertensive Antihypertensive AgentsAgents

HypertensionHypertension

High blood pressureHigh blood pressure• Normal:Normal: Systolic < 130 mmSystolic < 130 mm

Hg Diastolic < 85 mm HgHg Diastolic < 85 mm Hg

Classification of Blood Classification of Blood PressurePressureCategoryCategory Systemic BP (mm Hg)Systemic BP (mm Hg) Diastolic BP (mm Diastolic BP (mm Hg)Hg)

NormalNormal <130<130 <85<85

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

HypertensionHypertensionStage 1Stage 1 140-159140-159 90-9990-99

Stage 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 Classification of Blood PressurePressure

Primary HypertensionPrimary Hypertension• Specific cause unknownSpecific cause unknown• 90% of the cases90% of the cases• Also known as essential or idiopathic Also known as essential or idiopathic

hypertensionhypertension

Secondary HypertensionSecondary Hypertension• Cause is known (such as eclampsia of Cause is known (such as eclampsia of

pregnancy, renal artery disease, pregnancy, renal artery disease, pheochromocytoma)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

Blood Pressure = Blood Pressure = Cardiac Output X Peripheral ResistanceCardiac Output X Peripheral Resistance

Preload Contractility Preload Contractility Heart Heart

RateRate CirculatingCirculatingFluid VolumeFluid Volume

RenalRenalSodiumSodium

HandlingHandling

SympatheticSympatheticNervousNervousSystemSystem

ReninRenin AngiotensinAngiotensinAldosteroneAldosterone

SystemSystem

ArteriolarArteriolarVenousVenousVasoconstrictionVasoconstriction

VenousVenous

Vascular Vascular Smooth Smooth MuscleMuscle

Vascular remodelingVascular remodeling

V VVasomotor center

AfterloadAfterload

VolumeVolumeKidneysKidneys

PreloadPreload

Renin

Ang II

Aldosterone BP= CO x TPVRBP= CO x TPVR

11

22 11

11

Resistance arterioles Capacitance venules

Total Peripheral Vascular Resistance (TPVR)Total Peripheral Vascular Resistance (TPVR)

Ang I

Cardiac Output Cardiac Output HeartHeart

22

TPVRTPVR

VSMCsVSMCsVascularVascularSmooth Smooth MuscleMuscleCellsCells

Antihypertensive AgentsAntihypertensive Agents

• Medications used to treat Medications used to treat hypertensionhypertension

Therapeutic goals in hypertensionTherapeutic goals in hypertension

To lower the high blood pressure and To lower the high blood pressure and reduced cardiovascular morbidity and reduced cardiovascular morbidity and mortality by least intrusive means. mortality by least intrusive means.

For most of the HTN patients: life-long For most of the HTN patients: life-long treatment of an asymptomatic diseasetreatment of an asymptomatic disease

Antihypertensive AgentsAntihypertensive AgentsAntihypertensive AgentsAntihypertensive Agents

Antyhepertensive DrugsAntyhepertensive Drugs

New End-PointsNew End-Points

Effects on hard end-points Effects on hard end-points MortalityMortalityStrokeStrokeHeart attacksHeart attacks

Effects on end-organ damageEffects on end-organ damageLeft ventricular and vascular hypertophy Left ventricular and vascular hypertophy

Effects on renal functionEffects on renal function Effects on metabolic status Effects on metabolic status

Blood lipids and glucoseBlood lipids and glucose

Antihypertensive Agents: Antihypertensive Agents: CategoriesCategories

• Adrenergic agentsAdrenergic agents

• Angiotensin-converting enzyme Angiotensin-converting enzyme inhibitorsinhibitors

• Angiotensin II receptor blockersAngiotensin II receptor blockers

• Calcium channel blockersCalcium channel blockers

• DiureticsDiuretics

• VasodilatorsVasodilators


• Adrenergic AgentsAdrenergic Agents– Alpha1 blockersAlpha1 blockers– Beta blockers (cardioselective and Beta blockers (cardioselective and

nonselective)nonselective)– Centrally acting alpha blockersCentrally acting alpha blockers– Combined alpha-beta blockersCombined alpha-beta blockers– Peripheral-acting adrenergic agentsPeripheral-acting adrenergic agents

Beta Blockers Beta Blockers ( … lol)( … lol)Beta Blockers Beta Blockers ( … lol)( … lol)

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11

22 11

11


TPVRTPVR

Ang I


22

- Blockers- Blockers

VSMCsVSMCs

??

??

Beta BlockersBeta BlockersMechanisms and Sites of ActionMechanisms and Sites of Action

Beta BlockersBeta BlockersMechanisms and Sites of ActionMechanisms and Sites of Action

Negative ChronotropicNegative Chronotropic& Inotropic Effects& Inotropic Effects

Inhibition ofInhibition ofRenin ReleaseRenin Release

____________________________________________________________

- Reduction in cardiac output- Reduction in cardiac output- Inhibition of renin release- Inhibition of renin release- CNS effects- CNS effects- Reduction in venous return - Reduction in venous return and plasma volumeand plasma volume- Reduction in peripheral resistance- Reduction in peripheral resistance- Improvement in vascular - Improvement in vascular compliancecompliance- Resetting of baroreceptor levels- Resetting of baroreceptor levels- Effects on - Effects on prejunctionalprejunctionalreceptorsreceptors

- Attenuation of pressor response to - Attenuation of pressor response to catecholamines (stress, exercise) catecholamines (stress, exercise) ____________________________________________________________

Cardioselectivity Cardioselectivity (Beta-1 vs Beta-2 )(Beta-1 vs Beta-2 )

Intrinsic Sympathomimetic ActivityIntrinsic Sympathomimetic Activity (ISA; partial (ISA; partial agonistic activity)agonistic activity)

Affinity for alpha-1 adrenergic receptorsAffinity for alpha-1 adrenergic receptors (Labetalol, (Labetalol, Carvedilol)Carvedilol)

Beta BlockersBeta Blockers

There are 15 Beta blockers on the market in the US There are 15 Beta blockers on the market in the US Approved for Approved for hypertensionhypertension (13) and for one or more of following indications: (13) and for one or more of following indications:

Angina pectorisAngina pectoris Myocardial Infarction Myocardial Infarction Ventricular arrhythmiaVentricular arrhythmia Migraine prophylaxisMigraine prophylaxis Heart FailureHeart Failure Perioperative Hypertension Perioperative Hypertension


Beta Blockers ( …lol)Beta Blockers ( …lol)

Beta-1,2-Non-SelectiveBeta-1,2-Non-Selective PropranololPropranolol [INDERAL] [INDERAL]

Nadolol Nadolol [CORGARD][CORGARD]

Carteolol Carteolol [CARTROL] *[CARTROL] *

Timolol Timolol [BLOCADREN][BLOCADREN]

Pindolol Pindolol [VISKEN] *[VISKEN] * SotalolSotalol [BETAPACE] [BETAPACE]

Penbutol Penbutol [LEVATOL] *[LEVATOL] *

Beta-1-SelectiveBeta-1-Selective Acebutolol Acebutolol [SECTRAL] *[SECTRAL] *

Atenolol Atenolol [TENORMIN][TENORMIN]

Betaxolol Betaxolol [KERIONE][KERIONE]

BisoprololBisoprolol [ZEBETA] [ZEBETA] Esmolol Esmolol [BREVIBLOC] [BREVIBLOC]

MetoprololMetoprolol [LOPRESSOR ][LOPRESSOR ]

Beta-1,2/Alpha 1SelectiveBeta-1,2/Alpha 1Selective LabetalolLabetalol [TRANDATE, NORMODYNE] [TRANDATE, NORMODYNE]

Carvedilol Carvedilol [COREG][COREG]

* - ISA

XX

Side Effects: Side Effects: BronchospasmBronchospasm Bradicardia/heart blockBradicardia/heart block Mask and prolong the symptoms of hypoglycemiaMask and prolong the symptoms of hypoglycemia Abrupt withdrawal can precipitate MIAbrupt withdrawal can precipitate MI Cold extremities, Raynaud’s phenomenon, intermittent claudicationCold extremities, Raynaud’s phenomenon, intermittent claudication Decreased exercise tolerance; fatigue, depression and impotenceDecreased exercise tolerance; fatigue, depression and impotence CNS: sleep disturbance, vivid dreams, nightmaresCNS: sleep disturbance, vivid dreams, nightmares Effects of plasma lipids Effects of plasma lipids


YESYES: (useful in): (useful in)Younger patientsYounger patients

Anxious patientsAnxious patients

Angina pectorisAngina pectoris

Post-MI patientPost-MI patient


NoNo: (avoid in): (avoid in)Patients with COPD Patients with COPD IDDM IDDM Pateints with peripheral Pateints with peripheral

vascular disease vascular disease Raynaud’s syndromeRaynaud’s syndrome 2nd and 3rd degree block2nd and 3rd degree block Energetic patientsEnergetic patients

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

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11


TPVRTPVR

Ang I


22

11 Receptors Receptors

BlockersBlockers

11

11

11

11

11

11- Receptor Blockers- Receptor Blockers11- Receptor Blockers- Receptor Blockers

Inhibition of VasoconstrictionInhibition of VasoconstrictionInduced by EndogenousInduced by Endogenous

Catecholamines atCatecholamines atArterioles and VeinsArterioles and Veins

Reduced Peripheral ResistanceReduced Peripheral Resistanceandand

Reduced PreloadReduced Preload

Antihypertensive Agents: Antihypertensive Agents:


Alpha1 BlockersAlpha1 Blockers• doxazosin (Cardura)doxazosin (Cardura)

• prazosin (Minipress)prazosin (Minipress)

• terazosin (Hytrin)terazosin (Hytrin)



Central-Acting AdrenergicsCentral-Acting Adrenergics• Stimulate alpha2-adrenergic receptorsStimulate alpha2-adrenergic receptors

• Sympathetic outflow from the CNS is Sympathetic outflow from the CNS is decreaseddecreased

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 (drug of choice for hypertension in pregnancy)pregnancy)

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11


TPVRTPVR

Ang I


22

CentralCentralAgonistsAgonists

11

VSMCVSMC

X

X X

X

X

Diminished CNSDiminished CNSSympathetic OutflowSympathetic Outflow

Alpha-2 AgonistAlpha-2 Agonist

NE & EPINE & EPI

Pre-synaptic NeuronPre-synaptic Neuron

Alpha-2 ReceptorAlpha-2 Receptor

Alpha-1 ReceptorAlpha-1 ReceptorBeta ReceptorBeta Receptor

Post-synapticPost-synapticEffectorEffector

Activation of Pre-synapticActivation of Pre-synapticAlpha-2 Receptors ReducesAlpha-2 Receptors Reduces

NE & EPI Release at SynapseNE & EPI Release at Synapse

RostralRostralVentrolateralVentrolateral

MedullaMedulla

Central Central 22–Agonists–AgonistsCentral Central 22–Agonists–Agonists

Antihypertensive Agents: Antihypertensive Agents: Mechanism of ActionMechanism of ActionAdrenergic 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



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 Management of of severe CHF when

used used with cardiac glycosides and diureticswith cardiac glycosides and diuretics

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, dysmenorrhea, menopausal flushing, glaucomaglaucoma

– 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


Therapeutic UsesTherapeutic Uses• Adrenergic neuronal blockers Adrenergic neuronal blockers

(peripherally acting) (peripherally acting) – Treatment of hypertension, either alone Treatment of hypertension, either alone

or with other agentsor with other agents– Seldom used because of frequent side Seldom used because of frequent side

effectseffects


Side EffectsSide EffectsMost common:Most common: dry mouthdry mouthdrowsinessdrowsiness sedationsedationconstipationconstipation

Other:Other: headachesheadaches sleep disturbancessleep disturbancesnauseanausea rashrash

cardiac disturbances (palpitations)cardiac disturbances (palpitations)

HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSIONHIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION


Angiotensin-Converting Enzyme Angiotensin-Converting Enzyme InhibitorsInhibitors

(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

A n g i o t e n s i n II

Peripheral resistance Renal function

Cardiovascular structure

RapidPressor Response

1. Direct vasoconstriction

2. Enhancement of peripheral noradrenergic neurotransmission 3. Increased central (CNS) sympathetic discharge

4. Release of catecholamines from adrenal medulla

1. Increases Na+ reabsorption

2. Releases aldosterone from adrenal cortex

3. Altered renal hemodynamics: - renal vasoconstriction - increased noradrenergic neurotransmission in kidney - Increased renal sympathetic tone (CNS)

SlowPressor Response

Cardiovascular Hypertrophy and Remodeling

1. Non-hemodynamic effects: - Increased expression of proto-oncogenes - Increased production of growth factors - Increased synthesis of extracellular matrix proteins

2. Hemodynamic effects: - Increased afterload (cardiac) - Increased wall tension (vascular)

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11

22 11

11


TPVRTPVR

Ang I


22

ACE IACE Inhibitorsnhibitors

VSMCsVSMCs

Angiotensinogen Ang IAng II

Renin (renal)

Renin

Angiotensinogen

Angiotensinogen Ang I

mRNA

AT1

Ang II

AT1

A C E

ACE

(autocrine)

(paracrine)

(endocrine)

mRNARenin

mRNAA C E

endothelialcell

tissuetissue

(VSM cells)(VSM cells)

(myocyte ) (myocyte )

(liver)

mRNAA C E

mRNAmRNA

Renin

Angiotensinogen

Angiotensinogen

Ang IACE

Ang II

Local (tissue) RAS:Local (tissue) RAS:Intrinsic; Extrinsic

blood vessel

Bradykinin

A C E A C E

Kallikrein Renin

Angiotensin II

Angiotensin I

Angiotensinogen

Angiotensin Converting Enzyme

ACEIsACEIs

Kininogens

Inactive Peptides

BK receptorsBK receptors AT-1 receptorsAT-1 receptors

ACEIsACEIs

20 mmHg

Afferentarteriole

Bowman’scapsule

Efferentarteriole

Arterialpressure +

Angiotensin II+

Angiotensin II+ +

INTRAGLOMERULAR PRESSUREINTRAGLOMERULAR PRESSURE

excess glomerular pressure

hyperfiltration microalbuminuria

ACEIs : ACEIs : Prevention of renal disease Prevention of renal disease


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 angiotensin II, the result is potent vasoconstriction and stimulation of aldosteronevasoconstriction and 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


ACE InhibitorsACE Inhibitors• Aldosterone stimulates water and sodium Aldosterone stimulates water and sodium

resorption.resorption.

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

Antihypertensive Agents: Antihypertensive Agents: Mechanism of ActionMechanism of ActionACE InhibitorsACE Inhibitors• ACE Inhibitors block the angiotensin-ACE Inhibitors block the angiotensin-

converting enzyme, thus preventing the converting enzyme, thus preventing the formation of angiotensin II.formation of angiotensin II.

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

Result: decreased systemic vascular resistance Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore, (afterload), vasodilation, and therefore, decreased blood pressuredecreased 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 lisinopril (Prinivil and Zestril) and quinapril (Accupril)(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 UsesACE InhibitorsACE Inhibitors• HypertensionHypertension• CHF (either alone or in combination with CHF (either alone or in combination with

diuretics diuretics or other agents)or other agents)

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

• Renal protective effects in patients with Renal protective effects in patients with diabetesdiabetes

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

Antihypertensive Agents: Antihypertensive Agents: Side EffectsSide EffectsACE InhibitorsACE Inhibitors

• FatigueFatigue DizzinessDizziness

• HeadacheHeadache Mood changesMood changes

• Impaired tasteImpaired taste

Dry, nonproductive cough, reverses when therapy is Dry, nonproductive cough, reverses when therapy is stoppedstopped

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

Kininogens

Bradykinin

Inactive PeptidesA C E A C E

Kallikrein Renin

Endothelial Cell

Plasminogen Activators

Angiotensin II

Angiotensin I

Angiotensinogen

PAI-1 +

ACE Inhibitors vs AT1 Antagonists

++

tPA

A C E Is

PAI-1

Example: Fibrinolytic SystemExample: Fibrinolytic System

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11

22 11

11


TPVRTPVR

Ang I


22

Ang II ReceptorAng II ReceptorBlockersBlockers

VSMCsVSMCs

Ang II

Ang II


Angiotensin II Receptor BlockersAngiotensin II Receptor Blockers• Allow angiotensin I to be converted to Allow angiotensin I to be converted to

angiotensin II, but block the receptors that angiotensin II, but block the receptors that receive angiotensin IIreceive angiotensin II

• Block vasoconstriction and release of Block vasoconstriction and release of aldosteronealdosterone

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)

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

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


Calcium Channel BlockersCalcium Channel Blockers• BenzothiazepinesBenzothiazepines

• DihydropyridinesDihydropyridines

• PhenylalkylaminesPhenylalkylamines

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11


TPVRTPVR

Ang I


22

Calcium Channel Calcium Channel BlockersBlockers

CaCa++++

L-type CaL-type Ca++++ channelschannels

AV

11


Calcium Channel BlockersCalcium Channel Blockers• Cause smooth muscle relaxation by Cause smooth muscle relaxation by

blocking the binding of calcium to its blocking the binding of calcium to its receptors, preventing muscle contractionreceptors, preventing muscle contraction

• This causes decreased peripheral smooth This causes decreased peripheral smooth muscle tone, decreased systemic vascular muscle tone, decreased systemic vascular resistanceresistance

• Result: decreased blood pressureResult: decreased blood pressure

Calcium Channel BlockersCalcium Channel Blockers Mechanisms and Sites of Mechanisms and Sites of ActionAction

Calcium Channel BlockersCalcium Channel Blockers Mechanisms and Sites of Mechanisms and Sites of ActionAction

Negative Inotropic andNegative Inotropic andChronotropic EffectsChronotropic EffectsProduce VasorelaxationProduce Vasorelaxation

at Arteriolesat Arterioles

Reduced Peripheral ResistanceReduced Peripheral Resistance

Verap+Dilti>NifedVerap+Dilti>NifedNifed>Dilti+VerapNifed>Dilti+Verap

Block transmembrane entry of calcium into arteriolar smooth Block transmembrane entry of calcium into arteriolar smooth muscle cells and cardiac myocytes thus inhibiting excitation-muscle cells and cardiac myocytes thus inhibiting excitation-contractioncontraction

L-type CaL-type Ca++++ channels channels

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)


Calcium Channel BlockersCalcium Channel Blockers• AnginaAngina

• HypertensionHypertension

• DysrhythmiasDysrhythmias

• Migraine headachesMigraine headaches

Antihypertensive Agents: Antihypertensive Agents: Side EffectsSide EffectsCalcium 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: Antihypertensive Agents: DiureticsDiuretics

•Decrease the plasma and extracellular fluid Decrease the plasma and extracellular fluid volumesvolumes

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

resistanceresistance

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


VasodilatorsVasodilators

• Directly relaxes arteriolar smooth muscleDirectly relaxes arteriolar smooth muscle

• Result:Result: decreased systemic vascular decreased systemic vascular

response, response, decreased afterload, anddecreased afterload, and

PERIPHERAL PERIPHERAL

VASODILATIONVASODILATION

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)

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11


TPVRTPVR

Ang I


22

Peripheral Peripheral VasodilatorsVasodilators

11

NO NO →→ cGMP cGMP → → CaCa++++

22 11


VasodilatorsVasodilators• Treatment of hypertensionTreatment of hypertension

• May be used in combination with other May be used in combination with other agentsagents

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

Antihypertensive Agents: Side EffectsAntihypertensive Agents: Side EffectsVasodilatorsVasodilators

• 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

Antihypertensive Agents: Antihypertensive Agents: Nursing ImplicationsNursing Implications• Before beginning therapy, obtain a Before beginning therapy, obtain a

thorough health history and head-to-toe thorough health history and head-to-toe physical examination.physical examination.

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

• Assess for conditions that require Assess for conditions that require cautious use of these agents.cautious 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 missing a dose and taking the medications exactly as prescribed.exactly as prescribed.

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

• Monitor BP during therapy. Instruct patients Monitor BP during therapy. Instruct patients to 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 Remind patients that medications is only

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

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

• Encourage supervised exercise.Encourage supervised exercise.

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

slowly to avoid syncope from postural slowly to avoid syncope from postural hypotension.hypotension.

• Patients should report unusual shortness Patients should report unusual shortness of breath; difficulty breathing; swelling of of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; 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 Men taking these agents may not be aware

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

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

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

prolonged sitting or standing; physical prolonged sitting or standing; physical exercise; and alcohol ingestion may exercise; and alcohol ingestion may aggravate low blood pressure, leading to aggravate low blood pressure, leading to fainting and injury. Patients should 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 Patients should not take any other medications, including OTC drugs, without medications, including OTC drugs, without first getting the approval of their physician.first getting the 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

Diuretic AgentsDiuretic Agents


• Drugs that accelerate the rate of Drugs that accelerate the rate of urine formation.urine formation.

• Result: removal of sodium and waterResult: removal of sodium and water

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11

22 11

11


TPVRTPVR

Ang I


22

DIURETICSDIURETICS

VSMCsVSMCs

SodiumSodium

• Where sodium goes, water follows.Where sodium goes, water follows.

• 20 to 25% of all sodium is reabsorbed 20 to 25% of all sodium is reabsorbed into the bloodstream in the loop of into the bloodstream in the loop of Henle, Henle, 5 to 10% in the distal tubules, and 3% 5 to 10% in the distal tubules, and 3% in collecting ducts.in collecting ducts.

• If it is not absorbed, it is excreted with If it is not absorbed, it is excreted with the urine.the urine.

Inhibition ofInhibition ofSodium ReabsorptionSodium Reabsorption

Reduced Circulating VolumeReduced Circulating VolumeReduced PreloadReduced PreloadReduced Cardiac OutputReduced Cardiac Output

DiureticsDiuretics DiureticsDiuretics


• Carbonic anhydrase inhibitorsCarbonic anhydrase inhibitors

• Loop diureticsLoop diuretics

• Osmotic diureticsOsmotic diuretics

• Potassium-sparing diureticsPotassium-sparing diuretics

• Thiazide and thiazide-like diureticsThiazide and thiazide-like diuretics

Carbonic Anhydrase Carbonic Anhydrase InhibitorsInhibitors

(CAIs)(CAIs)• acetazolamide (Diamox)acetazolamide (Diamox)

• methazolamidemethazolamide

• dichlorphenamidedichlorphenamide

Carbonic Anhydrase Carbonic Anhydrase Inhibitors: Mechanism of Inhibitors: Mechanism of ActionAction• The enzyme carbonic anhydrase helps to The enzyme carbonic anhydrase helps to

make make H+ ions available for exchange with H+ ions available for exchange with sodium and water in the proximal tubules.sodium and water in the proximal tubules.

• CAIs block the action of carbonic CAIs block the action of carbonic anhydrase, thus preventing the exchange anhydrase, thus preventing the exchange of H+ ions with sodium of H+ ions with sodium and water.and water.

Carbonic Anhydrase Carbonic Anhydrase Inhibitors: Mechanism of Inhibitors: Mechanism of ActionAction• Inhibition of carbonic anhydrase reduces H+ Inhibition of carbonic anhydrase reduces H+

ion concentration in renal tubules.ion concentration in renal tubules.

• As a result, there is increased excretion of As a result, there is increased excretion of bicarbonate, sodium, water, and potassium.bicarbonate, sodium, water, and potassium.

• Resorption of water is decreased and urine Resorption of water is decreased and urine volume is increased.volume is increased.

Carbonic Anhydrase Carbonic Anhydrase Inhibitors: Therapeutic UsesInhibitors: Therapeutic Uses

• Adjunct agents in the long-term management Adjunct agents in the long-term management of open-angle glaucomaof open-angle glaucoma

• Used with miotics to lower intraocular pressure Used with miotics to lower intraocular pressure before ocular surgery in certain casesbefore ocular surgery in certain cases

• Also useful in the treatment of:Also useful in the treatment of:

– GlaucomaGlaucoma

– EdemaEdema

– EpilepsyEpilepsy

– High-altitude sicknessHigh-altitude sickness

Carbonic Anhydrase Carbonic Anhydrase Inhibitors: Therapeutic UsesInhibitors: Therapeutic Uses• Acetazolamide is used in the management of Acetazolamide is used in the management of

edema secondary to CHF when other diuretics edema secondary to CHF when other diuretics are not effective.are not effective.

• CAIs are less potent diuretics than loop CAIs are less potent diuretics than loop diuretics diuretics or thiazides—the metabolic acidosis they or thiazides—the metabolic acidosis they induce reduces their diuretic effect in 2 to 4 induce reduces their diuretic effect in 2 to 4 days.days.

Carbonic Anhydrase Carbonic Anhydrase Inhibitors: Inhibitors: Side EffectsSide EffectsMetabolic acidosisMetabolic acidosis DrowsinessDrowsiness

AnorexiaAnorexia ParesthesiasParesthesias

HematuriaHematuria UrticariaUrticaria

PhotosensitivityPhotosensitivity MelenaMelena

Loop DiureticsLoop Diuretics

• bumetanide (Bumex)bumetanide (Bumex)

• ethacrynic acid (Edecrin)ethacrynic acid (Edecrin)

• furosemide (Lasix)furosemide (Lasix)

Loop Diuretics: Loop Diuretics: Mechanism of ActionMechanism of Action• Act directly on the ascending limb of Act directly on the ascending limb of

the the loop of Henle to inhibit sodium and loop of Henle to inhibit sodium and chloride resorption.chloride resorption.

• Increase renal prostaglandins, resulting Increase renal prostaglandins, resulting in the dilation of blood vessels and in the dilation of blood vessels and reduced peripheral vascular resistance.reduced peripheral vascular resistance.

Loop Diuretics: Drug EffectsLoop Diuretics: Drug Effects

• Potent diuresis and subsequent loss of fluidPotent diuresis and subsequent loss of fluid

• Decreased fluid volume causes:Decreased fluid volume causes:– Reduced BPReduced BP

– Reduced pulmonary vascular resistanceReduced pulmonary vascular resistance

– Reduced systemic vascular resistanceReduced systemic vascular resistance

– Reduced central venous pressureReduced central venous pressure

– Reduced left ventricular end-diastolic pressureReduced left ventricular end-diastolic pressure

• Potassium depletionPotassium depletion

Loop Diuretics:Loop Diuretics:Therapeutic UsesTherapeutic Uses

• Edema associated with CHF or Edema associated with CHF or hepatic hepatic or renal diseaseor renal disease

• Control of hypertensionControl of hypertension

Loop Diuretics: Side EffectsLoop Diuretics: Side Effects

Body SystemBody System EffectEffect

CNSCNS Dizziness, headache, Dizziness, headache, tinnitus, blurred tinnitus, blurred

visionvision

GIGI Nausea, vomiting, Nausea, vomiting, diarrheadiarrhea

Loop Diuretics: Side EffectsLoop Diuretics: Side Effects

Body SystemBody System EffectEffect

HematologicHematologic Agranulocytosis, Agranulocytosis, neutropenia, neutropenia, thrombocytopeniathrombocytopenia

MetabolicMetabolic Hypokalemia, Hypokalemia, hyperglycemia,hyperglycemia,hyperuricemiahyperuricemia

Osmotic DiureticsOsmotic Diuretics

• mannitol (Resectisol, Osmitrol)mannitol (Resectisol, Osmitrol)

Osmotic Diuretics: Osmotic Diuretics: Mechanism of ActionMechanism of Action

• Work in the proximal tubuleWork in the proximal tubule

• Nonabsorbable, producing an Nonabsorbable, producing an osmotic effectosmotic effect

• Pull water into the blood vessels and Pull water into the blood vessels and nephrons from the surrounding nephrons from the surrounding tissuestissues

Osmotic Diuretics: Drug Osmotic Diuretics: Drug EffectsEffects• Reduced cellular edemaReduced cellular edema

• Increased urine production, causing Increased urine production, causing diuresisdiuresis

• Rapid excretion of water, sodium, and Rapid excretion of water, sodium, and other electrolytes, as well as excretion other electrolytes, as well as excretion of toxic substances from the kidneyof toxic substances from the kidney

• Reduces excessive intraocular pressureReduces excessive intraocular pressure

Osmotic Diuretics: Osmotic Diuretics: Therapeutic UsesTherapeutic Uses

• Used in the treatment of patients in Used in the treatment of patients in the early, oliguric phase of ARFthe early, oliguric phase of ARF

• To promote the excretion of toxic To promote the excretion of toxic substancessubstances

• Reduction of intracranial pressureReduction of intracranial pressure

• Treatment of cerebral edemaTreatment of cerebral edema

Osmotic Diuretics: Side Osmotic Diuretics: Side EffectsEffects

• ConvulsionsConvulsions

• ThrombophlebitisThrombophlebitis

• Pulmonary congestionPulmonary congestion

Also headaches, chest pains, tachycardia,Also headaches, chest pains, tachycardia,blurred vision, chills, and feverblurred vision, chills, and fever

Potassium-Sparing DiureticsPotassium-Sparing Diuretics

• amiloride (Midamor)amiloride (Midamor)

• spironolactone (Aldactone)spironolactone (Aldactone)

• triamterene (Dyrenium)triamterene (Dyrenium)

V VVasomotor center

AfterloadAfterload


PreloadPreload

Renin

Ang II


11

22 11

11


TPVRTPVR

Ang I


22

Aldosterone Aldosterone AntagonistsAntagonists

VSMCsVSMCs

Potassium-Sparing Potassium-Sparing Diuretics: Mechanism of Diuretics: Mechanism of ActionAction• Work in collecting ducts and distal Work in collecting ducts and distal

convoluted tubulesconvoluted tubules

• Interfere with sodium-potassium Interfere with sodium-potassium exchangeexchange

• Competitively bind to aldosterone Competitively bind to aldosterone receptorsreceptors

• Block the resorption of sodium and Block the resorption of sodium and water usually induced by aldosteronewater usually induced by aldosterone

Potassium-Sparing Potassium-Sparing Diuretics: Diuretics: Drug EffectsDrug Effects• Prevent potassium from being pumped Prevent potassium from being pumped

into the tubule, thus preventing its into the tubule, thus preventing its secretionsecretion

• Competitively block the aldosterone Competitively block the aldosterone receptors and inhibit its actionreceptors and inhibit its action

• The excretion of sodium and water The excretion of sodium and water is promotedis promoted

Potassium-Sparing Potassium-Sparing Diuretics: Therapeutic UsesDiuretics: Therapeutic Usesspironolactone and triamterenespironolactone and triamterene

• HyperaldosteronismHyperaldosteronism

• HypertensionHypertension

• Reversing the potassium loss caused by Reversing the potassium loss caused by

• potassium-losing drugspotassium-losing drugs

amilorideamiloride

• Treatment of CHFTreatment of CHF

Potassium-Sparing Potassium-Sparing Diuretics: Diuretics: Side EffectsSide EffectsBody SystemBody System EffectEffect

CNSCNS Dizziness, headacheDizziness, headache

GIGI Cramps, nausea, Cramps, nausea, vomiting, diarrheavomiting, diarrhea

OtherOther Urinary frequency,Urinary frequency,weaknessweakness**hyperkalemia**hyperkalemia

Potassium-Sparing Potassium-Sparing Diuretics: Diuretics: Side EffectsSide Effectsspironolactonespironolactone• gynecomastia, amenorrhea, irregular gynecomastia, amenorrhea, irregular

mensesmenses

Thiazide and Thiazide-Like Thiazide and Thiazide-Like DiureticsDiuretics• hydrochlorothiazide (Esidrix, HydroDIURIL)hydrochlorothiazide (Esidrix, HydroDIURIL)

• chlorothiazide (Diuril)chlorothiazide (Diuril)

• trichlormethiazide (Metahydrin)trichlormethiazide (Metahydrin)

• Thiazide-likeThiazide-like

• chlorthalidone (Hygroton)chlorthalidone (Hygroton)

• metolazone (Mykrox, Zaroxolyn)metolazone (Mykrox, Zaroxolyn)

Thiazide and Thiazide-Like Thiazide and Thiazide-Like Diuretics: Mechanism of ActionDiuretics: Mechanism of Action

• Inhibit tubular resorption of sodium and chloride ions

• Action primarily in the ascending loop of Henle and early distal tubule

• Result: water, sodium, and chloride are excreted

• Potassium is also excreted to a lesser extent

• Dilate the arterioles by direct relaxation

Thiazide and Thiazide-Like Thiazide and Thiazide-Like Diuretics: Drug EffectsDiuretics: Drug Effects

• Lowered peripheral vascular Lowered peripheral vascular resistanceresistance

• Depletion of sodium and waterDepletion of sodium and water

Thiazide and Thiazide-Like Thiazide and Thiazide-Like Diuretics: Therapeutic UsesDiuretics: Therapeutic Uses

•Hypertension Hypertension (one of the most prescribed group of (one of the most prescribed group of agents for this)agents for this)

•Edematous statesEdematous states

• Idiopathic hypercalciuriaIdiopathic hypercalciuria

•Diabetes insipidusDiabetes insipidus

•Adjunct agents in treatment of CHF, hepatic Adjunct agents in treatment of CHF, hepatic cirrhosiscirrhosis

Thiazide and Thiazide-Like Thiazide and Thiazide-Like Diuretics: Side EffectsDiuretics: Side Effects

Body SystemBody System EffectEffectCNSCNS Dizziness, headache, Dizziness, headache,

blurred vision, blurred vision, paresthesias,paresthesias, decreased libidodecreased libido

GIGI Anorexia, nausea, Anorexia, nausea, vomiting,vomiting, diarrheadiarrhea

Thiazide and Thiazide-Like Thiazide and Thiazide-Like Diuretics: Side EffectsDiuretics: Side Effects

Body SystemBody System EffectEffectGUGU ImpotenceImpotence

IntegumentaryIntegumentary Urticaria, Urticaria, photosensitivityphotosensitivity

MetabolicMetabolic Hypokalemia, Hypokalemia, glycosuria,glycosuria, hyperglycemia hyperglycemia

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications• Perform a thorough patient history and Perform a thorough patient history and

physical examination.physical examination.

• Assess baseline fluid volume status, intake Assess baseline fluid volume status, intake and output, serum electrolyte values, weight, and output, serum electrolyte values, weight, and vital signs.and vital signs.

• Assess for disorders that may contraindicate Assess for disorders that may contraindicate the use of, or necessitate cautious use of, the use of, or necessitate cautious use of, these agents.these agents.

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications• Instruct patients to take in the morning as Instruct patients to take in the morning as

much as possible to avoid interference with much as possible to avoid interference with sleep patterns.sleep patterns.

• Monitor serum potassium levels during Monitor serum potassium levels during therapy.therapy.

• Potassium supplements are usually not Potassium supplements are usually not recommended when potassium levels exceed recommended when potassium levels exceed 3.0 mEq/L.3.0 mEq/L.

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications• Teach patients to maintain proper nutritional Teach patients to maintain proper nutritional

and fluid volume status.and fluid volume status.

• Teach patients to eat more potassium-rich Teach patients to eat more potassium-rich foods when taking any but the potassium-foods when taking any but the potassium-sparing agents.sparing agents.

• Foods high in potassium include bananas, Foods high in potassium include bananas, oranges, dates, raisins, plums, fresh oranges, dates, raisins, plums, fresh vegetables, potatoes, meat, and fish.vegetables, potatoes, meat, and fish.

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications• Patients taking diuretics along with a Patients taking diuretics along with a

digitalis preparation should be taught to digitalis preparation should be taught to monitor for monitor for digitalis toxicity.digitalis toxicity.

• Diabetic patients who are taking thiazide Diabetic patients who are taking thiazide and/or and/or loop diuretics should be told to monitor loop diuretics should be told to monitor blood glucose and watch for elevated levels.blood glucose and watch for elevated levels.

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications• Teach patients to change positions slowly, and Teach patients to change positions slowly, and

to rise slowly after sitting or lying to prevent to rise slowly after sitting or lying to prevent dizziness and possible fainting related to dizziness and possible fainting related to orthostatic hypotension.orthostatic hypotension.

• Encourage patients to keep a log of their Encourage patients to keep a log of their daily weight.daily weight.

• Encourage patients to return for follow-up visits Encourage patients to return for follow-up visits and lab work.and lab work.

Diuretic Agents: Nursing Diuretic Agents: Nursing ImplicationsImplications• Patients who have been ill with nausea, Patients who have been ill with nausea,

vomiting, and/or diarrhea should notify vomiting, and/or diarrhea should notify their physician as fluid loss may be their physician as fluid loss may be dangerous.dangerous.

• Signs and symptoms of hypokalemia Signs and symptoms of hypokalemia include muscle weakness, constipation, include muscle weakness, constipation, irregular pulse rate, and overall feeling of irregular pulse rate, and overall feeling of lethargy.lethargy.

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications• Instruct patients to notify the physician Instruct patients to notify the physician

immediately if they experience rapid heart immediately if they experience rapid heart rates or syncope (reflects hypotension or rates or syncope (reflects hypotension or fluid loss).fluid loss).

• A weight gain of 2 or more pounds a day A weight gain of 2 or more pounds a day or 5 or more pounds a week should be or 5 or more pounds a week should be reported immediately.reported immediately.

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications

Monitor for adverse effects:Monitor for adverse effects:• metabolic alkalosis, drowsiness, lethargy, metabolic alkalosis, drowsiness, lethargy,

hypokalemia, tachycardia, hypotension, hypokalemia, tachycardia, hypotension, leg leg cramps, restlessness, decreased mental cramps, restlessness, decreased mental alertnessalertness

Diuretic Agents: Diuretic Agents: Nursing ImplicationsNursing Implications

• Monitor for therapeutic effects:Monitor for therapeutic effects:– Reduction in edema, fluid volume Reduction in edema, fluid volume

overload, CHF overload, CHF – Reduction of hypertensionReduction of hypertension– Return to normal intraocular pressuresReturn to normal intraocular pressures

Antilipemic AgentsAntilipemic Agents

AntilipemicsAntilipemics

• Drugs used to lower lipid levelsDrugs used to lower lipid levels

Triglycerides and Triglycerides and CholesterolCholesterol

• Two primary forms of lipids in the Two primary forms of lipids in the bloodblood

• Water-insoluble fats that must be Water-insoluble fats that must be bound to apoproteins, specialized bound to apoproteins, specialized lipid-carrying proteinslipid-carrying proteins

• Lipoprotein is the the combination of Lipoprotein is the the combination of triglyceride or cholesterol with triglyceride or cholesterol with apoproteinapoprotein

Types of LipoproteinsTypes of Lipoproteins

LipidLipid ProteinProteinContent Lipoprotein ClassificationContent Lipoprotein Classification ContentContent

MostMost chylomicronchylomicron LeastLeast

very-low density lipoprotein very-low density lipoprotein (VLDL)(VLDL)

Intermediate-density lipoproteinIntermediate-density lipoprotein(IDL)(IDL)

LeastLeast High-density lipoprotein (HDL)High-density lipoprotein (HDL) MostMost

Instructors may want to Instructors may want to insert insert

EIC Image #84: EIC Image #84:

Cholesterol HomeostasisCholesterol Homeostasis

Coronary Heart DiseaseCoronary Heart Disease

• The risk of CHD in patients with The risk of CHD in patients with cholesterol levels of 300 mg/dL is 3 cholesterol levels of 300 mg/dL is 3 to 4 times greater than that in to 4 times greater than that in patients with levels less than patients with levels less than 300 mg/dL300 mg/dL

AntilipemicsAntilipemics

• Bile acid sequestrantsBile acid sequestrants

• HMG-CoA reductase inhibitors HMG-CoA reductase inhibitors (HMGs or statins)(HMGs or statins)

• Fibric acid derivativesFibric acid derivatives

• Niacin (nicotinic acid)Niacin (nicotinic acid)

Antilipemics: Bile Acid Antilipemics: Bile Acid Sequestrants Sequestrants

• cholestyramine (Questran)cholestyramine (Questran)

• colestipol hydrochloride (Colestid)colestipol hydrochloride (Colestid)

• Also called bile acid-binding resins Also called bile acid-binding resins and and ion-exchange resinsion-exchange resins


Mechanism of ActionMechanism of Action• Prevent resorption of bile acids from small Prevent resorption of bile acids from small

intestineintestine

• Bile acids are necessary for absorption Bile acids are necessary for absorption of cholesterolof cholesterol


Therapeutic UsesTherapeutic Uses• Type II hyperlipoproteinemiaType II hyperlipoproteinemia

• Relief of pruritus associated with partial Relief of pruritus associated with partial biliary obstruction (cholestyramine)biliary obstruction (cholestyramine)

Antilipemics: Bile Acid Antilipemics: Bile Acid SequestrantsSequestrants

Side EffectsSide Effects

• ConstipationConstipation– Heartburn, nausea, belching, bloatingHeartburn, nausea, belching, bloating

These adverse effects tend to disappear These adverse effects tend to disappear over timeover time

Antilipemics: HMG-CoA Antilipemics: HMG-CoA Reductase Inhibitors (HMGs Reductase Inhibitors (HMGs or statins)or statins)• lovastatin (Mevacor)lovastatin (Mevacor)

• pravastatin (Pravachol)pravastatin (Pravachol)

• simvastatin (Zocor)simvastatin (Zocor)

• atorvastatin (Lipitor)atorvastatin (Lipitor)

• cerivastatin (Baycol)cerivastatin (Baycol)

• fluvastatin (Lescol)fluvastatin (Lescol)

Most potent LDL reducersMost potent LDL reducers

Antilipemics: Antilipemics: HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitorsMechanism of ActionMechanism of Action• Inhibit HMG-CoA reductase, which is used Inhibit HMG-CoA reductase, which is used

by the liver to produce cholesterolby the liver to produce cholesterol

• Lower the rate of cholesterol productionLower the rate of cholesterol production

Antilipemics: Antilipemics: HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitorsTherapeutic UsesTherapeutic Uses• Treatment of type IIa and IIb Treatment of type IIa and IIb

hyperlipidemiashyperlipidemias– Reduce LDL levels by 30 to 40%Reduce LDL levels by 30 to 40%– Increase HDL levels by 2 to 15%Increase HDL levels by 2 to 15%– Reduce triglycerides by 10 to 30%Reduce triglycerides by 10 to 30%

Antilipemics: Antilipemics: HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitorsSide EffectsSide Effects• Mild, transient GI disturbancesMild, transient GI disturbances

• RashRash

• HeadacheHeadache

• Myopathy (muscle pain)Myopathy (muscle pain)

• Elevations in liver enzymesElevations in liver enzymes

Antilipemics: Fibric Acid Antilipemics: Fibric Acid Derivatives Derivatives

• clofibrateclofibrate

• gemfibrozil (Lopid)gemfibrozil (Lopid)

• fenofibrate (Tricor)fenofibrate (Tricor)

Antilipemics: Fibric Acid Antilipemics: Fibric Acid Derivatives Derivatives

Mechanism of ActionMechanism of Action

• Believed to work by activating lipase, Believed to work by activating lipase, which breaks down cholesterolwhich breaks down cholesterol

• Also suppress release of free fatty Also suppress release of free fatty acid from the adipose tissue, inhibit acid from the adipose tissue, inhibit synthesis of triglycerides in the liver, synthesis of triglycerides in the liver, and increase the secretion of and increase the secretion of cholesterol in the bilecholesterol in the bile

Antilipemics: Fibric Acid Antilipemics: Fibric Acid DerivativesDerivatives

Therapeutic UsesTherapeutic Uses

• Treatment of type IV and V Treatment of type IV and V hyperlipemiashyperlipemias

• Treatment of type III, IV, and V Treatment of type III, IV, and V hyperlipidemiashyperlipidemias

Decrease the triglyceride levels and increaseDecrease the triglyceride levels and increaseHDL by as much as 25%HDL by as much as 25%

Antilipemics: Fibric Acid Antilipemics: Fibric Acid DerivativesDerivatives

Side EffectsSide Effects• Abdominal discomfortAbdominal discomfort

• DiarrheaDiarrhea

• NauseaNausea

• Blurred visionBlurred vision

• Increased risk of gallstonesIncreased risk of gallstones

• Prolonged prothrombin timeProlonged prothrombin time

• Liver studies may show increased Liver studies may show increased functionfunction

Antilipemics: Niacin Antilipemics: Niacin (Nicotinic Acid)(Nicotinic Acid)

• Vitamin BVitamin B33

• Lipid-lowering properties require Lipid-lowering properties require much higher doses than when used much higher doses than when used as a vitaminas a vitamin

• Effective, inexpensive, often used in Effective, inexpensive, often used in combination with other lipid-lowering combination with other lipid-lowering agentsagents


Mechanism of ActionMechanism of Action• Thought to increase activity of lipase, Thought to increase activity of lipase,

which breaks down lipidswhich breaks down lipids

• Reduces the metabolism or catabolism of Reduces the metabolism or catabolism of cholesterol and triglyceridescholesterol and triglycerides


Therapeutic UsesTherapeutic Uses• Effective in lowering triglyceride, total Effective in lowering triglyceride, total

serum cholesterol, and LDL levelsserum cholesterol, and LDL levels

• Increases HDL levelsIncreases HDL levels

• Effective in the treatment of types IIa, IIb, Effective in the treatment of types IIa, IIb, III, IV, III, IV, and V hyperlipidemiasand V hyperlipidemias


Side EffectsSide Effects• Flushing (due to histamine release)Flushing (due to histamine release)

• PruritusPruritus

• GI distressGI distress

Antilipemics: Nursing Antilipemics: Nursing ImplicationsImplications• Before beginning therapy, obtain a Before beginning therapy, obtain a

thorough health and medication history.thorough health and medication history.

• Assess dietary patterns, exercise level, Assess dietary patterns, exercise level, weight, height, VS, tobacco and alcohol weight, height, VS, tobacco and alcohol use, family history.use, family history.

• Assess for contraindications, conditions that Assess for contraindications, conditions that require cautious use, and drug interactions.require cautious use, and drug interactions.

Antilipemics: Nursing Antilipemics: Nursing ImplicationsImplications• Contraindications include biliary Contraindications include biliary

obstruction, liver dysfunction, active obstruction, liver dysfunction, active liver disease.liver disease.

• Obtain baseline liver function studies.Obtain baseline liver function studies.

• Patients on long-term therapy may Patients on long-term therapy may need supplemental fat-soluble vitamins need supplemental fat-soluble vitamins (A, D, K).(A, D, K).

• Take with meals to decrease GI upset.Take with meals to decrease GI upset.

Antilipemics: Nursing Antilipemics: Nursing ImplicationsImplications• Patient must be counseled concerning diet and Patient must be counseled concerning diet and

nutrition on an ongoing basis.nutrition on an ongoing basis.

• Instruct on proper procedure for taking the Instruct on proper procedure for taking the medications.medications.

• Powder forms must be taken with a liquid, mixed Powder forms must be taken with a liquid, mixed thoroughly but not stirred, and NEVER taken dry.thoroughly but not stirred, and NEVER taken dry.

• Other medications should be taken 1 hour before Other medications should be taken 1 hour before or 4 to 6 hours after meals to avoid interference or 4 to 6 hours after meals to avoid interference with absorption.with absorption.

Antilipemics: Nursing Antilipemics: Nursing ImplicationsImplications• Clofibrate often causes constipation; Clofibrate often causes constipation;

instruct patients to increase fiber and fluid instruct patients to increase fiber and fluid intake to offset this effect.intake to offset this effect.

• To minimize side effects of niacin, start on To minimize side effects of niacin, start on low initial dose and gradually increase it, low initial dose and gradually increase it, and take with meals.and take with meals.

• Small doses of aspirin or NSAIDs may be Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to taken 30 minutes before niacin to minimize cutaneous flushing.minimize cutaneous flushing.

Antilipemics: Nursing Antilipemics: Nursing ImplicationsImplications

• Inform patients that these agents Inform patients that these agents may take several weeks to show may take several weeks to show effectiveness.effectiveness.

• Instruct patients to report persistent Instruct patients to report persistent GI upset, constipation, abnormal or GI upset, constipation, abnormal or unusual bleeding, and yellow unusual bleeding, and yellow discoloration of the skin.discoloration of the skin.

Antilipemics: Nursing Antilipemics: Nursing ImplicationsImplications

• Monitor for side effects, including Monitor for side effects, including increased liver enzyme studies.increased liver enzyme studies.

• Monitor for therapeutic effects:Monitor for therapeutic effects:– Reduced cholesterol and triglyceride Reduced cholesterol and triglyceride

levelslevels

Documents

Antihypertensive Agents