ANTIHYPERTENSIVE ANTIHYPERTENSIVE AGENTS AGENTS

UNDER THE GUIDANCE OF UNDER THE GUIDANCE OF DURRAI ANAND KUMARDURRAI ANAND KUMAR

FROM FROM G.SHRAVANIG.SHRAVANI170213884010170213884010

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 PressureClassification of Blood Pressure

CategoryCategory 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 90-9990-99Stage 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 Also known as essential or idiopathic

hypertensionhypertensionSecondary 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

ββ 11

ββ 22 αα 11

ββ 11

Resistance arterioles Capacitance venules

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

Ang I

Cardiac Output Cardiac Output HeartHeart

αα 22

TPVRTPVR

VSMCsVSMCsVascularVascularSmooth Smooth MuscleMuscleCellsCells

Antihypertensive AgentsAntihypertensive Agents

• Medications used to treat hypertensionMedications used to treat hypertension

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 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 Left ventricular and vascular

hypertophy 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 inhibitorsAngiotensin-converting enzyme inhibitors• Angiotensin II receptor blockersAngiotensin II receptor blockers• Calcium channel blockersCalcium channel blockers• DiureticsDiuretics• VasodilatorsVasodilators

Antihypertensive Agents: Antihypertensive Agents: CategoriesCategories

• 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

Antihypertensive Agents: Antihypertensive Agents: CategoriesCategoriesCalcium Channel BlockersCalcium Channel Blockers• BenzothiazepinesBenzothiazepines• DihydropyridinesDihydropyridines• PhenylalkylaminesPhenylalkylamines

V VVasomotor center

AfterloadAfterload

VolumeVolumeKidneysKidneys

PreloadPreload

Renin

Ang II

Aldosterone BP= CO x TPVRBP= CO x TPVR

ββ 11

Resistance arterioles Capacitance venules

TPVRTPVR

Ang I

Cardiac Output Cardiac Output HeartHeart

αα 22

Calcium Channel Calcium Channel BlockersBlockers

CaCa++++

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

AV

ββ 11

Antihypertensive Agents: Antihypertensive Agents: Mechanism of ActionMechanism of ActionCalcium 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 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

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)

NIFIDIPINENIFIDIPINE

• It is synthesized by a Hanisch synthesis It is synthesized by a Hanisch synthesis from two molecules of a from two molecules of a ββ-dicarbonyl -dicarbonyl compound methyl acetoacetate, using as compound methyl acetoacetate, using as the aldehydes component 2-the aldehydes component 2-nitrobenzaldehyde and ammonianitrobenzaldehyde and ammonia

CHO

NO2

2-nitrobenzaldehyde

+H3C

COOCH3

O

2

methyl 3-oxobutanoate

NO2

COOCH3

CH3O

COOCH3COOCH3

O

O

CH3

CH3

NO2

(Z)-methyl 2-(2-nitrobenzylidene)-3-oxobutanoate

NH

NO2

COOCH3

CH3

COOCH3

CH3

NH3

Antihypertensive Agents: Antihypertensive Agents: Therapeutic UsesTherapeutic UsesCalcium Channel BlockersCalcium Channel Blockers

• AnginaAngina

• HypertensionHypertension

• DysrhythmiasDysrhythmias

• Migraine headachesMigraine headaches

Advantages:Advantages:• Unlike diuretics no adverse metabolic effects but mild Unlike diuretics no adverse metabolic effects but mild

• adverse effects like – dizziness, fatigue etc.adverse effects like – dizziness, fatigue etc.

• Do not compromise haemodynamics – no impairment of work capacityDo not compromise haemodynamics – no impairment of work capacity

• No sedation or CNS effectNo sedation or CNS effect

• Can be given to asthma, angina and PVD patientsCan be given to asthma, angina and PVD patients

• No renal and male sexual function impairmentNo renal and male sexual function impairment

• No adverse verse fetal effects and can be given in pregnancyNo adverse verse fetal effects and can be given in pregnancy

• Minimal effect Minimal effect onon quality of life quality of life

Current status:Current status:

• ´As per JNC 7 CCBs are not 1stline of antihypertensive unless ´As per JNC 7 CCBs are not 1stline of antihypertensive unless indicated – ACEI/diuretics/beta blockers´indicated – ACEI/diuretics/beta blockers´

• However its been used as 1stline by many because of excellent However its been used as 1stline by many because of excellent tolerability and high efficacytolerability and high efficacy

• Preferred in elderly and prevents strokePreferred in elderly and prevents stroke

• CCBs are effective in low Rennin hypertension´CCBs are effective in low Rennin hypertension´

• They are next to ACE inhibitors in inhibition of albuminuria They are next to ACE inhibitors in inhibition of albuminuria and prevention of diabetic nephropathy´and prevention of diabetic nephropathy´

• Immediate acting Nifedipine is not encouraged anymoreImmediate acting Nifedipine is not encouraged anymore

• Unstable anginaUnstable angina

• Heart failureHeart failure

• HypotensionHypotension

• Post infarct casesPost infarct cases

• Severe aortic stenosisSevere aortic stenosis

PREPARATION AND DOSAGEPREPARATION AND DOSAGE

Amlodipine – 2.5, 5 and 10 mg tablets (5-10 Amlodipine – 2.5, 5 and 10 mg tablets (5-10 mg OD) –Stamlo, Amlopres, Amlopin etc.mg OD) –Stamlo, Amlopres, Amlopin etc.

• Nimodipine – 30 mg tab and 10 mg/50 ml Nimodipine – 30 mg tab and 10 mg/50 ml injection –injection –

• Vasotop, Nimodip, Nimotide etc.Vasotop, Nimodip, Nimotide etc.