藥物誘導的麻醉.ppt

Thestateofgeneralanesthesiaisdruginducedabsenceofperceptionofallsensations,PRINCIPLESOFTHEADMINISTRATIONOFGENERALANAESTHETICS,UptakeandDistributionofinhalationalgeneralanestheticsDepthofAnesthesia-Tensionofanaestheticagentinbrain-controls-ratesofinductionandrecoveryTensionandpartialpressureareinterchangeableterms,Tensioninthearterialbloodandbrainaresameandaredeterminedby:,ConcentrationoftheanaestheticintheinspiredairdependsonrateofventilationTransferofthegasfromthealveolitothebloodDecreasedindisease(ex.emphysema)Rateoftransferisdeterminedby:Solubility(Bloodgaspartitioncoefficient.)Rateofbloodflow(directlyproportionaltotheC.O.Partialpressuresoftheagentinarterialandmixedvenousblood.Lossoftheagentfromthearterialbloodtoallthetissueofthebody,ANAESTHESIAMACHINES,AredevicesbywhichtheanesthesiologistisabletodeliverMeasuredquantitiesofanaestheticgasesandoxygenthroughaccurateflowmetersandwiththeuseofspecialvaporizersitispossibletoaddthevaporofvolatileanestheticliquidtothegasstream.ThemixtureofoxygenandanaestheticagentisthendeliveredtoabreathingcircuitforadministrationbyInhalation.,GeneralAnestheticsarethemostdangerousdrugsTherapeuticindexrangesbetween2-42-3timesdosecausescirculatoryfailure,Oraldosedeliversthetotaldose,WhengasorvaporisinhaledonlyasmallamountisabsorbedWhereastherestisexhaledoutinnext1-2secondsThedrugreachesthebrainbyleavingthebloodAnaestheticbloodlevelsofthesecannotbemeasuresaccuratelyConcentrationsinthelungscanbeeasilyfrequentlyandaccuratelybemeasuredThepartialspressuresoftheanaestheticinthelungandthebrainarealmostequalatequilibrium,MinimumAlveolarConcentration,MACisthemeasureofpotencyofgeneralanestheticsItistheminimumalveolarconcentration(MAC)atoneatmosphericpressurethatproducesimmobilityin50%patientsoranimalsexposedtonoxiousstimuli,ELIMINATIONOFGENERALANAESTHETICS,Freegasesandvaporswashoutofthelungs:Thearterialbloodtensiondeclinesfirst.Followedbythatinthetissueswheretheanaestheticagentpersistsforalongertime.Tissuehavinglowbloodflow(muscle)relievetheagentmuchslowly.OTHERROUTES:Theseagentsarealsoeliminatedinsmallerquantitiesfromskin,mucousmembraneandthekidneys,StagesofGeneralAnaesthesia,DEPTHOFGENERALANAESTHESIAOCCURSINSTAGES,STAGE-1ANALGESIASTAGE-2DELERIUMSTAGE-3SURGICALANESTHESIASTAGE-4MEDULLARYPARALYSES,APPROACHESFORTESTINGDEPTHOFANAESTHESIA,Blinkingofeyelidsonstrikingtheeyelashes.SwallowingRegularityanddepthofrespiration.IncreaseinrespiratoryrateandB.P.onincisionTightnessofjawmuscles.Aboveresponsesfadeondeepeningoftheanesthesia.,DeepanesthesiaLeedsto:RespiratorydepressionApneaLoweringofB.P.Asystole,PREANAESTHETICMEDICATIONDecreaseanxietywithoutdrowsinessAmnesiaRelievepreoperativepainDecreaserequirementforaninhalationalagent.Minimisingundesirableeffectsofanesthetics.(salivation,decreaseinheartrate,coughing,vomiting)Decreasevolumeandacidityofthegastriccontents.Decreasestressresponseinpreoperativeperiod,PREANAESTHETICMEDICATION2-3drugsareusedconcomitantly:SedativesHypnoticsAntianxietydrugsOpoidsAntiemeticsH-2antagonistsGastrokineticagentsAnticholinergics,DRUGSUSEDINPREANAESTHETICMEDICATIONSBenzodiazepines:Diazepam,Lorazepam,Midazolam.Barbibiturates:Pentobarbitone,secobarbitone.Antihistamines:Hydroxyzine,Diphenhydramine.Phenothiazines:Promethazine.Butyrophenones:Droperidol.Opoids:Morphine,fentanyl,meperidine.Anticholinergics:atropine,scopolamine,glycopyrrolate.Antiemetics:OndansetronDrugsdecreasinggastricacidity:H-2antagonists.Antacids.Gastrokineticagents.,MECHANISMOFACTIONSOFGENERALANAESTHETICSAlldrugsbelongtodiversegroupsInertgasesasxenonInorganic/OrganiccompdsasNitrousoxideandChloroform.ComplexOrganicMoleculesHalogenatedAlkanesandethersTheModeofactioniswithoutanysatisfactoryexplanation.POSTULATIONS:Influencesynaptictransmission.Axonalconductionisunaffected.Potentiatereleaseofinhibitoryneurotransmitters.Inhibitexcitatorysynapses.,MECHANISMOFACTIONSOFGENERALANAESTHETICSActionoftheseagentsisonLipidbilayerand/orproteinlipidinterfaceORIONCHANNELS(Na/K/Ca)ORLigandgatedChannelsl-Glutamate.NMDANAChRGABA-A,Atthemolecularlevel,anestheticsprobablyexerttheireffectsbydirectinteractionswithproteinsratherthanbydisturbingthematrixofthelipidbilayerasearlierpostulated.AnestheticsMaybindtohydrophobicpocketsorclefts,producingsmallchangesinproteinConformationalertingreceptorofchannelfunction.ItisalsopossiblethatspecializedareasOfthemembranesuchastheboundarylipidssurroundingmembraneProteinsareimportantsitesofanaestheticbindingandaction.,MECHANISMOFACTIONSOFGENERALANAESTHETICS,MECHANISMOFACTION:Theexactmechanismbywhichinhalationalanestheticsfunctionisnotknown.Thereappearstobeacorrelationbetweenanestheticpotencyandlipidsolubility(Meyer-Overtontheory),suggestingthattheseanestheticslikelyaffectthelipidmatrixofnervecellmembranesinthebrain.Furthermore,NMRandelectronspinresonancestudiesindicatethatanestheticscausealocaldisorderingofthelipidmembranematrix,possiblydecreasingthenumberofmoleculesthatalternatesimultaneouslybetweenthegelandcrystallinestates,andtherebyalteringmembranefunction.,NEUROLEPTANALGESIA-Stateofquiescence-Reducedmotoractivity-Reducedanxiety-IndifferencetothesurroundingswithoutlossofconsciousnessThepatientrespondstocommands.Drugs:aneuroleptcompd(Droperidol)plusanopoidanalgesic(fentanyl)Neuroleptanalgesiamaybeconvertedintoneuroleptanaesthesiabyconcominantadministrationof65%nitrousoxide,DISSOCIATIVEANAESTHESIAastateofsedation,immobility,amnesiaandmarkedanalgesia(feelingofdissociation)asingledrugsuchasketaminecanresultinthisstate.,Inhalationagents:NEWERAGENTSOLDERDRUGSHalothaneChloroformEnfluraneEtherVolatileliquids:IsofluraneEthylchlorideDesfluraneTrichlorethyleneSevofluraneGases:Nitrouso