《药理学》英文课件 Anti hypertensive Drugs

AntihypertensiveDrugsOVERVIEWHypertensionisdefinedasasustaineddiastolicbloodpressuregreaterthan90mmHgaccompaniedbyanelevatedsystolicbloodpressure(>140mmHg).canleadtocongestiveheartfailure,myocardialinfarction,renaldamage,andcerebrovascularaccidents.ETIOLOGYOFHYPERTENSIONmorethan90%ofpatientshaveessentialhypertension,adisorderofunknownoriginaffectingthebloodpressure-regulatingmechanism.InheritancefactorsEnvironmentalfactorssuchasastressfullifestyle,highdietaryintakeofsodium,obesity,MECHANISMSFORCONTROLLINGBLOODPRESSURE

Inbothnormalandhypertensiveindividuals,cardiacoutputandperipheralresistancearecontrolledmainlybytwooverlappingcontrolmechanisms:thebaroreflexesmediatedbythesym-patheticnervoussystem,andtherenin-angiotensin-aldosteronesystemTREATMENTSTRATEGIESMildhypertensioncanoftenbecontrolledwithasingledrug.Moreseverehypertensionmayrequiretreatmentwithseveraldrugsthatareselectedtominimizeadverseeffectsofthecombinedregimen.Treatmentisinitiatedwithanyoffourdrugsdependingontheindividualpatient:adiuretic,abeta-blocker,anACEinhibitor,oracalciumchannelblocker.DIURETICSDiureticsarecurrentlyrecommendedasthefirst-linedrugtherapyforhypertension.Low-dosediuretictherapyissafeandeffectiveinpreventingstroke,myocardialinfarction,congestiveheartfailureandtotalmortality.ThiazidediureticsAlloraldiureticdrugsareeffectiveinthetreatmentofhypertension,butthethiazideshavefoundthemostwidespreaduse.Actionshydrochlorothiazidelowerbloodpressure,initiallybyincreasingsodiumandwaterexcretion.Thiscausesadecreaseinextracellularvolume,resultinginadecreaseincardiacoutputandrenalbloodflow.Withlong-termtreatment,plasmavolumeapproachesanormalvalue,butperipheralresistancedecreases.Therapeuticusesinboththesupineandstandingpositions;posturalhypotensionisrarelyobserved.usefulincombinationtherapywithavarietyofotherantihypertensiveagentsincludingbeta-blockersandACEinhibitors.areparticularlyusefulinthetreatmentofblackorelderlypatients,andinthosewithchronicrenaldisease.ThiazidediureticsarenoteffectiveinpatientswithinadequatekidneyfunctionPharmacokineticsThiazidediureticscanbeadministeredorally.Theyinduceconsiderabledisturbancesinelectrolytebalance.Forexample,bloodlevelsofK+andMg++arereduced,andCa++isretainedbythebodyAdverseeffectsinducehypokalemiaandhyperuricemiain70%ofpatients,andhyperglycemiain10%ofpatients.SerumpotassiumlevelsshouldbemonitoredcloselyinpatientswhoarepredisposedtocardiacarrhythmiasDiureticsshouldbeavoidedinthetreatmentofhypertensivediabeticsorpatientswithhyperlipidemia.beta-ADRENOCEPTORBLOCKINGAGENTSbeta-Blockersand/ordiureticsarecurrentlyrecommendedasfirst-linedrugtherapyforhypertension.Thesedrugsareefficaciousbuthavesomecontraindications.ActionsThebeta-blockersreducebloodpressureprimarilybydecreasingcardiacoutput.TheymayalsodecreasesympatheticoutflowfromtheCNSandinhibitthereleaseofreninfromthekidneys,thusdecreasingtheformationofangiotensinIIandsecretionofaldosterone.TherapeuticusesSubsetsofthehypertensivepopulation:Thebeta-blockersaremoreeffectivefortreatinghypertensioninwhitethaninblackpatients,andinyoungpatientscomparedtotheelderly.Conditionsthatdiscouragetheuseofbeta-blockers(forexample,severechronicobstructivelungdisease,chroniccongestiveheartfailure,severesymptomaticocclusiveperipheralvasculardisease)aremorecommonlyfoundintheelderlyandindiabetics.]TherapeuticusesHypertensivepatientswithconcomitantdiseases:Thebeta-blockersareusefulintreatingconditionsthatmaycoexistwithhypertension,suchassupraventriculartachyarrhythmia,previousmyocardialinfarction,anginapectoris,AdverseeffectsDrugwithdrawal:Abruptwithdrawalmaycausereboundhypertension,probablyasaresultofup-regulationofbeta-receptors.ACEINHIBITORSThesedrugsblocktheangiotensinconvertingenzymethatcleavesangiotensinItoformthepotentvasoconstrictor,angiotensinIIActions:TheACEinhibitorslowerbloodpressurebyreducingperipheralvascularresistancewithoutreflexlyincreasingcardiacoutput,rate,orcontractility.Therapeuticuses

Likebeta-blockers,ACEinhibitorsaremosteffectiveinhypertensivepatientswhoarewhiteandyoung.However,whenusedincombinationwithadiuretic,theeffectivenessofACEinhibitorsissimilarinwhiteandblackhypertensivepatients.Unlikebeta-blockers,ACEinhibitorsareeffectiveinthemanagementofpatientswithchroniccongestiveheartfailure.ACEinhibitorsarenowastandardinthecareofapatientfollowingamyocardialinfarction.Therapyisstarted24hoursaftertheendoftheinfarction.CALCIUMCHANNELBLOCKERSDiphenylalkylamines:Benzothiazepines:Dihydropyridines:ActionsCalciumchannelantagonistsblocktheinwardmovementofcalciumbybindingtoL-typecalciumchannelsintheheartandinsmooth-muscleofthecoronaryandperipheralvasculature.Thiscausesvascularsmoothmuscletorelax,dilatingmainlyarterioles.

Therapeuticuseshaveanintrinsicnatriureticeffect;therefore,theydonotusuallyrequiretheadditionofadiuretic.areusefulinthetreatmentofhypertensivepatientswhoalsohaveasthma,diabetes,angina,and/orperipheralvasculardisease.CENTRALLY-ACTINGADRENERGICDRUGSClonidine

actionsdiminishescentraladrenergicoutflow.Clonidineisusedprimarilyforthetreatmentofmildtomoderatehyperte