《药理学》英文课件 Antianginal Drugs

AntianginalDrugsOVERVIEWAnginapectorisisacharacteristicchestpaincausedbycoronarybloodflowthatisinsufficienttomeettheoxygendemandsofthemyocardium.ORGANICNITRATESOrganicnitratesaresimplenitricandnitrousacidestersofalcohols.Thesecompoundscausearapidreductioninmyocardialoxygendemandfollowedbyrapidreliefofsymptoms.Theyareeffectiveinstableandunstableangina,aswellasPrinzmetal'sorvariantanginapectoris.NitroglycerinNitrates,beta-blockers,andcalciumchannelblockersareequallyeffectiveforreliefofanginalsymptoms.However,forpromptreliefofanongoingattackofanginaprecipitatedbyexerciseoremotionalstress,sublingual(orsprayform)nitroglycerinisthedrugofchoice.Mechanismsofactionnitroglycerinarethoughttorelaxvascularsmoothmusclebytheirintracellularconversiontonitriteionsandthentonitricoxide(NO),whichinturnactivatesguanylate

cyclaseandincreasesthecells'cyclicGMP.ElevatedcGMPultimatelyleadstodephosphorylationofthemyosinlightchain,resultinginvascularsmoothmusclerelaxation.

EffectsoncardiovascularsystemFirst,itcausesdilationofthelargeveins,resultinginpoolingofbloodintheveins.Thisdiminishespreload(venousreturntotheheart),andreducestheworkoftheheart.Second,nitroglycerindilatesthecoronaryvasculature,providingincreasedbloodsupplytotheheartmuscle.Nitroglycerincausesadecreaseinmyocardialoxygenconsumptionbecauseofdecreasedcardiacwork.PharmacokineticsThetimetoonsetofactionvariesfromoneminutefornitroglycerintomorethanonehourforisosorbide

mononitrate.Significantfirst-passmetabolismofnitroglycerinoccursintheliver.eithersublinguallyorviaatransdermal

AdverseeffectsThemostcommonadverseeffectofnitroglycerin,aswellastheothernitrates,isheadache.Thirtytosixtypercentofpatientsreceivingintermittentnitratetherapywithlong-actingagentsdevelopheadaches.Highdosesoforganicnitratescanalsocauseposturalhypotension,facialflushing,andtachycardia.ToleranceTolerancetotheactionsofnitratesdevelopsrapidly.Itcanbeovercomebyprovisionofadaily"nitrate-freeinterval"torestoresensitivitytothedrug.Thisintervalistypically6to8hours,usuallyatnightbecausethereisdecreaseddemandontheheartatthattime.beta-ADRENERGICBLOCKERSbeta-adrenergicblockingagentssuppresstheactivationoftheheartbyblockingbeta-receptors.Theyalsoreducetheworkoftheheartbydecreasingcardiacoutputandcausingaslightdecreaseinbloodpressure.Propranololistheprototypeofthisclassofcompounds.Thebeta-blockersreducethefrequencyandseverityofanginaattacks.Theseagentsareparticularlyusefulinthetreatmentofpatientswithmyocardialinfarction.Thebeta-blockerscanbeusedwithnitratestoincreaseexercisedurationandtolerance.contraindicatedinpatientswithdiabetes,peripheralvasculardisease,orchronicobstructivepulmonarydisease.CALCIUMCHANNELBLOCKERSThecalciumchannelblockersinhibittheentranceofcalciumintocardiacandsmoothmusclecellsofthecoronaryandsystemicarterialbeds.Allcalciumchannelblockersarethereforevasodilatorsthatcauseadecreaseinsmoothmuscletoneandvascularresistance.Atclinicaldoses,theseagentsaffectprimarilytheresistanceofvascularsmoothmuscleandthemyocardium.NifedipineNifedipinefunctionsmainlyasanarteriolarvasodilator.Thisdrughasminimaleffectoncardiacconductionorheartrate.Nifedipineisadministeredorallyandhasashorthalf-life(about4hours)requiringmultipledosing.Thevasodilationeffectofnifedipineisusefulinthetreatmentofvariantanginacausedbyspontaneouscoronaryspasm.sideeffectsNifedipinecancauseflushing,headache,hypotension,andperipheraledemaassideeffectsofitsvasodilationactivity.Thedrugmaycausereflextachycardiaifperipheralvasodilationismarkedresultinginasubstantialdecreaseinbloodpressure.Verapamil

Verapamilslowscardiacconductiondirectlyandthusdecreasesheartrateandoxygendemand.Verapamilcausesgreaternegativeinotropiceffectsthandoesnifedipine,butitisaweakervasodilator.Diltiazem

Diltiazemhascardiovasculareffectsthataresimilartothoseofverapamil.Itreducestheheartrate,althoughtoalesserextentthanverapamil,andalsodecreasesbloodpressure.Inaddi-tion,diltiazemcanrelievecoronaryarteryspasmandisthereforeparticularlyusefulinpatientswithvariantangina.Theincidenceofadversesideeffectsislow.showstreatmentofanginainpatientswithconcomitantdiseases.contraindicatio