antihypertensive agents. calcium channel blockers

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  • ANTIHYPERTENSIVE AGENTS UNDER THE GUIDANCE OF DURRAI ANAND KUMAR

    FROM G.SHRAVANI170213884010

  • HypertensionHigh blood pressureNormal:Systolic < 130 mmHg Diastolic < 85 mm Hg

  • Classification of Blood PressureCategorySystemic BP (mm Hg)Diastolic BP (mm Hg)Normal
  • Classification of Blood PressurePrimary HypertensionSpecific cause unknown90% of the casesAlso known as essential or idiopathic hypertensionSecondary HypertensionCause is known (such as eclampsia of pregnancy, renal artery disease, pheochromocytoma)10% of the cases

  • Blood Pressure = CO x SVRCO = Cardiac outputSVR = Systemic vascular resistance

  • Blood Pressure = Cardiac Output X Peripheral ResistancePreload Contractility Heart Rate CirculatingFluid VolumeRenalSodiumHandlingSympatheticNervousSystemRenin AngiotensinAldosteroneSystemArteriolarVenousVasoconstrictionVenousVascular Smooth MuscleVascular remodeling

  • VVVasomotor centerAfterloadVolumeKidneysPreloadReninAng IIAldosteroneBP= CO x TPVRb1b2a1b1Resistance arteriolesCapacitance venulesTotal Peripheral Vascular Resistance (TPVR)Ang ICardiac Output Hearta2TPVRVSMCsVascularSmooth MuscleCells

  • Antihypertensive AgentsMedications used to treat hypertension

  • Therapeutic goals in hypertension To lower the high blood pressure and reduced cardiovascular morbidity and mortality by least intrusive means.

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

    Antihypertensive Agents

  • Antyhepertensive Drugs New End-Points Effects on hard end-points MortalityStrokeHeart attacksEffects on end-organ damageLeft ventricular and vascular hypertophy Effects on renal functionEffects on metabolic status Blood lipids and glucose

  • Antihypertensive Agents: CategoriesAdrenergic agentsAngiotensin-converting enzyme inhibitorsAngiotensin II receptor blockersCalcium channel blockersDiureticsVasodilators

  • Antihypertensive Agents: CategoriesAdrenergic AgentsAlpha1 blockersBeta blockers (cardioselective and nonselective)Centrally acting alpha blockersCombined alpha-beta blockersPeripheral-acting adrenergic agents

  • Antihypertensive Agents: CategoriesCalcium Channel BlockersBenzothiazepinesDihydropyridinesPhenylalkylamines

  • VVVasomotor centerAfterloadVolumeKidneysPreloadReninAng IIAldosteroneBP= CO x TPVRb1Resistance arteriolesCapacitance venulesTPVRAng ICardiac Output Hearta2Calcium Channel BlockersCa++ L-type Ca++ channelsAVb1

  • Antihypertensive Agents: Mechanism of ActionCalcium Channel BlockersCause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contractionThis causes decreased peripheral smooth muscle tone, decreased systemic vascular resistanceResult: decreased blood pressure

  • Calcium Channel Blockers Mechanisms and Sites of ActionNegative Inotropic andChronotropic EffectsProduce Vasorelaxationat ArteriolesReduced Peripheral ResistanceVerap+Dilti>NifedNifed>Dilti+VerapBlock transmembrane entry of calcium into arteriolar smooth muscle cells and cardiac myocytes thus inhibiting excitation-contraction

    L-type Ca++ channels

  • Antihypertensive Agents Calcium Channel BlockersBenzothiazepines:diltiazem (Cardizem, Dilacor)Phenylalkamines:verapamil (Calan, Isoptin)Dihydropyridines:amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene)nifedipine (Procardia), nimodipine (Nimotop)

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

  • Antihypertensive Agents: Therapeutic UsesCalcium Channel BlockersAnginaHypertensionDysrhythmiasMigraine headaches

  • Advantages:Unlike diuretics no adverse metabolic effects but mild

    adverse effects like dizziness, fatigue etc.

    Do not compromise haemodynamics no impairment of work capacity

    No sedation or CNS effect

    Can be given to asthma, angina and PVD patients

    No renal and male sexual function impairment

    No adverse verse fetal effects and can be given in pregnancy

    Minimal effect on quality of life

  • Current status:As per JNC 7 CCBs are not 1stline of antihypertensive unless indicated ACEI/diuretics/beta blockersHowever its been used as 1stline by many because of excellent tolerability and high efficacyPreferred in elderly and prevents strokeCCBs are effective in low Rennin hypertensionThey are next to ACE inhibitors in inhibition of albuminuria and prevention of diabetic nephropathyImmediate acting Nifedipine is not encouraged anymore

  • Unstable angina

    Heart failure

    Hypotension

    Post infarct cases

    Severe aortic stenosis

  • PREPARATION AND DOSAGEAmlodipine 2.5, 5 and 10 mg tablets (5-10 mg OD) Stamlo, Amlopres, Amlopin etc.Nimodipine 30 mg tab and 10 mg/50 ml injection Vasotop, Nimodip, Nimotide etc.

  • *In interest of time we can not discuss in details all factors that may affect blood pressure level pathophysiology and

    Blood pressure is controlled by an integrated system and the major elements that control the level of blood pressure are presented of this slide. Cardiac output, peripheral vascular resistance and blood volume. **CCB exert theirs clinical effects by blocking the L-class of voltage gated calcium channels. Calcium plays a critical role in cellular communication, regulation and function any manipulation of transmembrane Ca+ influx can affect variety of cellular functions and regulatoryt processes.

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