AnesthesiaRelatedDrugs

Researchers,techniciansandcarepersonsmusthaveknowledgeoftheactions,methodsofadministration,and
nursingconsiderationsassociatedwitheachdrugusedinourlaboratory.Drugsarecommonlyplacedintocategories
accordingtotheirsimilaritiesinactionand/ortheirphysiologiceffectwhenintroducedintothesystem.The
followingtwosectionsdescribethebasiccategoriesofdrugscommonlyusedinourlaboratory.Whilethesetwo
chaptershavesomedetaileddescriptionsofdrugsthatareimportantforourlaboratory,theyarestillusefulforthe
nonspecialist,astheyexplainthespecificusesofthesedrugsinthelaboratory,andtheirdosagesfordifferent
procedures.

Anticholinergics
Anticholinergicagentsmaybeindicatedpriortotheadministrationofavarietyofanestheticandrelatedagents,
includingsedatives,narcotics,barbiturates,andinhalantanestheticagents.Atropinesulfate,scopolamine,and
glycopyrrolatearethethreeprincipleanticholinergicsusedinthelaboratory.Allthreesubstancesareantimuscarinic
agents.MuscarinicreceptorantagonistspreventtheeffectsofAChbyblockingitsbindingtomuscariniccholinergic
receptorsatneuroeffectorsitesonsmoothmuscle,cardiacmuscle,andglandcells;inperipheralganglia;andinthe
centralnervoussystem.
Ingeneral,muscarinicreceptorantagonistscauselittleblockadeoftheeffectsofAChatnicotinicreceptorsites.
Thus,atautonomicganglia,wheretransmissionprimarilyinvolvesanactionofAChonnicotinicreceptors,atropine
producespartialblockonlyatrelativelyhighdoses.Attheneuromuscularjunction,wherethereceptorsare
principallyorexclusivelynicotinic,extremelyhighdosesofatropineorrelateddrugsarerequiredtocauseany
degreeofblockade.However,quaternaryammoniumanalogsofatropineandrelateddrugsgenerallyexhibita
greaterdegreeofnicotinicblockingactivityand,consequently,arelikelytointerferewithganglionicor
neuromusculartransmissionindosesthatmorecloselyapproximatethosethatproducemuscarinicblock.Inthe
CNS,cholinergictransmissionappearstobepredominantlynicotinicinthespinalcordandbothmuscarinicand
nicotinicatsubcorticalandcorticallevelsinthebrain.Autoradiographicstudieshaverevealedawidespread
distributionofmuscarinicreceptorsthroughoutthehumanbrain.Morerecentstudiesusingmuscarinicreceptor
subtypespecificantibodiesdemonstratediscretelocalizationofthesesubtypeswithinbrainregions.Manyormost
oftheCNSeffectsoftherapeuticdosesofatropinelikedrugsareprobablyattributabletotheircentralmuscarinic
blockade.Athighortoxicdoses,thecentraleffectsofatropineandrelateddrugsgenerallyconsistofstimulation
followedbydepression.Sincequaternarycompoundspenetratethebloodbrainbarrierpoorly,antagonistsofthis
typehavelittleornoeffectontheCNS.
Parasympatheticneuroeffectorjunctionsindifferentorgansarenotequallysensitivetothemuscarinicreceptor
antagonists.Smalldosesofmuscarinicreceptorantagonistsdepresssalivaryandbronchialsecretionandsweating.
Withlargerdoses,thepupildilates,accommodationofthelenstonearvisionisinhibited,andvagaleffectsonthe
heartareblockedsothattheheartrateisincreased.Largerdosesinhibittheparasympatheticcontroloftheurinary
bladderandgastrointestinaltract,thereininhibitingmicturitionanddecreasingthetoneandmotilityofthegut.Still
largerdosesarerequiredtoinhibitgastricsecretionandmotility.Thus,dosesofatropineandmostrelated
muscarinicreceptorantagoniststhatreducegastrointestinaltoneanddepressgastricsecretionalsoalmost
invariablyaffectsalivarysecretion,ocularaccommodation,andmicturition.Thishierarchyofrelativesensitivities
probablyisnotaconsequenceofdifferencesintheaffinityofatropineforthemuscarinicreceptorsatthesesites,
becauseatropinedoesnotshowselectivitytowarddifferentmuscarinicreceptorsubtypes.Morelikelydeterminants
includethedegreetowhichthefunctionsofvariousendorgansareregulatedbyparasympathetictoneandthe
involvementofintramuralneuronsandreflexes.
Themuscarinicreceptorantagonistsblocktheresponsesofthesphinctermuscleoftheirisandtheciliarymuscleof
thelenstocholinergicstimulation.Thus,theydilatethepupil(mydriasis)andparalyzeaccommodation(cycloplegia).


Thewidepupillarydilatationresultsinphotophobia;thelensisfixedforfarvision,nearobjectsareblurred,and
objectsmayappearsmallerthantheyare.Thenormalpupillaryreflexconstrictiontolightoruponconvergenceof
theeyesisabolished.Theseeffectscanoccuraftereitherlocalorsystemicadministrationofthealkaloids.However,
conventionalsystemicdosesofatropine(0.6mg)havelittleoculareffect,incontrasttoequaldosesofscopolamine,
whichcausedefinitemydriasisandlossofaccommodation.Locallyappliedatropineorscopolamineproducesocular
effectsofconsiderableduration;accommodationandpupillaryreflexesmaynotfullyrecoverfor7to12days.The
muscarinicreceptorantagonistsusedasmydriaticsdifferfromthesympathomimeticagentsinthatthelattercause
pupillarydilatationwithoutlossofaccommodation.Pilocarpine,cholineesters,physostigmine,andisoflurophate
(DFP)insufficientconcentrationscanpartiallyorfullyreversetheoculareffectsofatropine.
Muscarinicreceptorantagonistsadministeredsystemicallyhavelittleeffectonintraocularpressureexceptin
patientswithnarrowangleglaucoma,wherethepressuremayoccasionallyrisedangerously.Theriseinpressure
occurswhentheanteriorchamberisnarrowandtheirisobstructsentryofaqueoushumorintothetrabeculae.This
interfereswithdrainageofaqueoushumor.Thedrugsmayprecipitateafirstattackinunrecognizedcasesofthis
rarecondition.Inpatientswithopenangleglaucoma,anacuteriseinpressureisunusual.Atropinelikedrugs
generallycanbeusedsafelyinthislattercondition,particularlyifthepatientisalsoadequatelytreatedwithan
appropriatemioticagent.
AtropineSulfate
Description::Itactsdirectlyonthesmoothmusclesandsecretoryglandsinnervatedbypostganglioniccholinergic
nerves,blockingtheparasympathomimeticeffectsofacetylcholine.PenetratestheBloodBrainbarrier.
Usage:Asapreanestheticitisusedbothbecauseofthemildrespiratorystimulationbecauseitinhibitssalivary
secretion.Inreversingparalysisitisusedinconjunctionwiththeadministrationofprostigmintoblockthe
muscarinicreceptors.Administrationofprostigminwithoutatropinecancauseparasympathetichyperactivity.
AtropineisdistributedassuchbyElkinsSinn,EliLillyandAstra.
DosageandAdministration:Aspreanesthetic0.05mg/kgToreverseparalysis0.15mg/kgWeusuallyusethe
0.54mg/mlconcentration.Forthisconcentrationthedosageforatropineaspreanestheticis0.1ml/kg.
Robinul
Description:Glycopyrrolate,likeotheranticholinergic(antimuscarinic)agents,inhibitstheactionofacetylcholineon
structuresinnervatedbypostganglioniccholinergicnervesandonsmoothmusclesthatrespondtoacetylcholinebut
lackcholinergicinnervation.Theseperipheralcholinergicreceptorsarepresentintheautonomiceffectorcellsof
smoothmuscle,cardiacmuscle,thesinoatrialnode,theatrioventricularnode,exocrineglands,and,toalimited
degree,intheautonomicganglia.Thus,itdiminishesthevolumeandfreeacidityofgastricsecretionsandcontrols
excessivepharyngeal,tracheal,andbronchialsecretions.
Glycopyrrolateantagonizesmuscarinicsymptoms(e.g.,bronchorrhea,bronchospasm,bradycardia,andintestinal
hypermotility)inducedbycholinergicdrugssuchastheanticholinesterases.Thehighlypolarquaternaryammonium
groupofglycopyrrolatelimitsitspassageacrosslipidmembranes,suchasthebloodbrainbarrier,incontrastto
atropinesulfateandscopolaminehydrobromide,whicharenonpolartertiaryamineswhichpenetratelipidbarriers
easily.
Peakeffectsoccurapproximately30to45minutesafterintramuscularadministration.Thevagalblockingeffects
persistfor2to3hoursandtheantisialagogueeffectspersistupto7hours,periodslongerthanforatropine.With
intravenousinjection,theonsetofactionisgenerallyevidentwithinoneminute.


Usage:Inanesthesia:Robinul(glycopyrrolate)Injectableisindicatedforuseasapreoperativeantimuscarinicto
reducesalivary,tracheobronchial,andpharyngealsecretions;toreducethevolumeandfreeacidityofgastric
secretions;and,toblockcardiacvagalinhibitoryreflexesduringinductionofanesthesiaandintubation.When
indicated,RobinulInjectablemaybeusedintraoperativelytocounteractdruginducedorvagaltractionreflexeswith
theassociatedarrhythmias.Glycopyrrolateprotectsagainsttheperipheralmuscariniceffects(e.g.,bradycardiaand
excessivesecretions)ofcholinergicagentssuchasneostigmineandpyridostigminegiventoreversethe
neuromuscularblockadeduetonondepolarizingmusclerelaxants.Investigateanytachycardiabeforegiving
glycopyrrolatesinceanincreaseintheheartratemayoccur.Usewithcautioninmonkeyswithcardiacarrhythmias
orhypertension.
Incaseofoverdosage,tocombatperipheralanticholinergiceffects,aquaternaryammoniumanticholinesterase
suchasneostigminemethylsulfate(whichdoesnotcrossthebloodbrainbarrier)maybegivenintravenouslyin
incrementsof0.25mginadults.Thisdosagemayberepeatedeveryfivetotenminutesuntilanticholinergic
overactivityisreversedoruptoamaximumof2.5mg.Proportionatelysmallerdosesshouldbeusedinchildren.
Indicationforrepetitivedosesofneostigmineshouldbebasedonclosemonitoringofthedecreaseinheartrateand
thereturnofbowelsounds.IntheunlikelyeventthatCNSsymptoms(excitement,restlessness,convulsions,
psychoticbehavior)occur,physostigmine(whichdoescrossthebloodbrainbarrier)shouldbeused.Physostigmine
0.5to2mgshouldbeslowlyadministeredintravenouslyandrepeatedasnecessaryuptoatotalof5mginadults.
Proportionatelysmallerdosesshouldbeusedinchildren.Fevershouldbetreatedsymptomatically.Intheeventofa
curarelikeeffectonrespiratorymuscles,artificialrespirationshouldbeinstitutedandmaintaineduntileffective
respiratoryactionreturns.
DosageandAdministration:Robinul(glycopyrrolate)Injectablemaybeadministeredintramuscularly,or
intravenously,withoutdilution,inthefollowingindications:
Preanestheticmedication.TherecommendeddoseofRobinul(glycopyrrolate)Injectableinchildren1monthto
12yearsofageis0.002mg(0.01mL)perpoundofbodyweightintramuscularly,given30to60minutespriortothe
anticipatedtimeofinductionofanesthesiaoratthetimethepreanestheticnarcoticand/orsedativeare
administered.Children1monthto2yearsofagemayrequireupto0.004mg(0.02mL)perpoundofbodyweight.
Intraoperativemedication.BecauseofthelongdurationofactionofRobinul(glycopyrrolate)ifusedas
preanestheticmedication,additionalRobinul(glycopyrrolate)Injectableforanticholinergiceffectintraoperativelyis
rarelyneeded;intheeventitisrequiredtherecommendedpediatricdoseis0.002mg(0.01mL)perpoundofbody
weightintravenously,nottoexceed0.1mg(0.5mL)inasingledosewhichmayberepeated,asneeded,atintervals
of23minutes.Theusualattemptsshouldbemadetodeterminetheetiologyofthearrhythmia,andthesurgicalor
anestheticmanipulationsnecessarytocorrectparasympatheticimbalanceshouldbeperformed.
Reversalofneuromuscularblockade.TherecommendedpediatricdoseofRobinul(glycopyrrolate)Injectableis
0.2mg(1.0mL)foreach1.0mgofneostigmineor5.0mgofpyridostigmine.Inordertominimizetheappearanceof
cardiacsideeffects,thedrugsmaybeadministeredsimultaneouslybyintravenousinjectionandmaybemixedinthe
samesyringe.

Anticholinesterases
Theseagentsinhibitacetylcholinesterase(antiChE),whichisconcentratedinsynapticregionsandisresponsiblefor
therapidhydrolysisofacetylcholine.Transmitterthusaccumulates,andtheresponsetoAChthatisliberatedby
cholinergicimpulsesorthatisspontaneouslyreleasedfromthenerveendingisenhanced.Theanticholinesterases
reversetheantagonismcausedbycompetitiveneuromuscularblockingagents.


ThecardiovascularactionsofantiChEagentsarecomplex,sincetheyreflectbothganglionicandpostganglionic
effectsofaccumulatedAChontheheartandbloodvessels.Thepredominanteffectontheheartfromtheperipheral
actionofaccumulatedAChisbradycardia,resultinginafallincardiacoutput.Higherdosesusuallycauseafallin
bloodpressure,oftenasaconsequenceofeffectsofantiChEagentsonthemedullaryvasomotorcentersofthe
CNS.
AntiChEagentsaugmentvagalinfluencesontheheart.Thisshortenstheeffectiverefractoryperiodofatrial
musclefibers,andincreasestherefractoryperiodandconductiontimeattheSAandAVnodes.Thebloodvessels
areingeneraldilated,althoughthecoronaryandpulmonarycirculationmayshowtheoppositeresponse.Atthe
ganglioniclevel,accumulatingAChinitiallyisexcitatoryonnicotinicreceptors,butathigherconcentrations,
ganglionicblockadeensuesasaresultofpersistentdepolarizationofthecellmembrane.Theexcitatoryactionon
theparasympatheticganglioncellswouldtendtoreinforcethediminishedcardiacoutput,whereastheopposite
sequencewouldresultfromtheactionofAChonsympatheticganglioncells.Excitationfollowedbyinhibitionalsois
producedbyAChatthemedullaryvasomotorandcardiaccenters.Alloftheseeffectsarecomplicatedfurtherbythe
hypoxemiaresultingfromthebronchoconstrictorandsecretoryactionsofincreasedAChontherespiratorysystem;
hypoxemia,inturn,wouldreinforcebothsympathetictoneandAChinduceddischargeofepinephrinefromthe
adrenalmedulla.Hence,itisnotsurprisingthatanincreaseinheartrateisseenwithseverecholinesteraseinhibitor
poisoning.
TheeffectsofantiChEdrugsontheCNSlikewisearecharacterizedbystimulationorfacilitationatvarioussites,
succeededbyinhibitionorparalysisathigherconcentrations.HypoxemiaisprobablyamajorfactorinCNS
depressionthatappearsafterlargedosesofantiChEagents.Thestimulanteffectsareantagonizedbyatropine,
althoughnotascompletelyasarethemuscariniceffectsatperipheralautonomiceffectorsites.
Prostigmin(neostigminemethylsulfate)
Description:Prostigmin(neostigminemethylsulfate)Injectable,ananticholinesteraseagent,isasterileaqueous
solutionintendedforintramuscular,intravenousorsubcutaneousadministration.ProstigminInjectableisavailable
inthefollowingconcentrations:Prostigmin1:2000Ampouleseachmlcontains0.5mgneostigminemethylsulfate
compoundedwith0.2%parabens(methylandpropyl)aspreservativesandsodiumhydroxidetoadjustpHto
approximately5.9.
Prostigmin1:1000MultipleDoseVialseachmlcontains1mgneostigminemethylsulfatecompoundedwith
0.45%phenolaspreservative,0.2mgsodiumacetate,andaceticacidandsodiumhydroxidetoadjustpHto
approximately5.9.Prostigmin1:2000MultipleDoseVialseachmlcontains0.5mgneostigminemethylsulfate
compoundedwith0.45%phenolaspreservative,0.2mgsodiumacetate,andaceticacidandsodiumhydroxideto
adjustpHtoapproximately5.9.Chemically,neostigminemethylsulfateis(mhydroxyphenyl)trimethylammonium
methylsulfatedimethylcarbamate.Ithasamolecularweightof334.39
Neostigmineinhibitsthehydrolysisofacetylcholinebycompetingwithacetylcholineforattachmentto
acetylcholinesteraseatsitesofcholinergictransmission.Itenhancescholinergicactionbyfacilitatingthe
transmissionofimpulsesacrossneuromuscularjunctions.Italsohasadirectcholinomimeticeffectonskeletal
muscleandpossiblyonautonomicganglioncellsandneuronsofthecentralnervoussystem.Neostigmineundergoes
hydrolysisbycholinesteraseandisalsometabolizedbymicrosomalenzymesintheliver.Proteinbindingtohuman
serumalbuminrangesfrom15to25percent.Followingintramuscularadministration,neostigmineisrapidly
absorbedandeliminated.Inastudyoffivepatientswithmyastheniagravis,peakplasmalevelswereobservedat30
minutes,andthehalfliferangedfrom51to90minutes.Approximately80percentofthedrugwaseliminatedin
urinewithin24hours;approximately50%astheunchangeddrug,and30percentasmetabolites.Following
intravenousadministration,plasmahalfliferangesfrom47to60minuteshavebeenreportedwithameanhalflife


of53minutes.Theclinicaleffectsofneostigmineusuallybeginwithin20to30minutesafterintramuscularinjection
andlastfrom2.5to4hours.
Prostigmindoesnotantagonize,andmayinfactprolong,thePhaseIblockofDepolarizingmusclerelaxantssuch
assuccinylcholineordecamethonium.Certainantibiotics,especiallyneomycin,streptomycinandkanamycin,havea
mildbutdefinitenondepolarizingblockingactionwhichmayaccentuateneuromuscularblock.Theseantibiotics
shouldbeusedinthemyasthenicpatientonlywheredefinitelyindicated,andthencarefuladjustmentshouldbe
madeoftheanticholinesterasedosage.Localandsomegeneralanesthetics,antiarrhythmicagentsandotherdrugs
thatinterferewithneuromusculartransmissionshouldbeusedcautiously,ifatall,inpatientswithmyasthenia
gravis;thedoseofProstigminmayhavetobeincreasedaccordingly.
OverdosageofProstigmincancausecholinergiccrisis,whichischaracterizedbyincreasingmuscleweakness,and
throughinvolvementofthemusclesofrespiration,mayresultindeath.Myastheniccrisis,duetoanincreaseinthe
severityofthedisease,isalsoaccompaniedbyextrememuscleweaknessandmaybedifficulttodistinguishfrom
cholinergiccrisisonasymptomaticbasis.However,suchdifferentiationisextremelyimportantbecauseincreasesin
thedoseofProstigminorotherdrugsinthisclass,inthepresenceofcholinergiccrisisorofarefractoryor
"insensitive"state,couldhavegraveconsequences.
Usage:Forthereversalofeffectsofnondepolarizingneuromuscularblockingagents:
DosageandAdministration:WhenProstigminisadministeredintravenously,itisrecommendedthatatropine
sulfate(0.6to1.2mg)alsobegivenintravenouslyusingseparatesyringes.Someauthoritieshaverecommendedthat
theatropinebeinjectedseveralminutesbeforetheProstigminratherthanconcomitantly.Theusualdoseis0.5to2
mgProstigmingivenbySlowintravenousinjection,repeatedasrequired.Onlyinexceptionalcasesshouldthetotal
doseofProstigminexceed5mg.Itisrecommendedthatthepatientbewellventilatedandapatentairway
maintaineduntilcompleterecoveryofnormalrespirationisassured.Theoptimumtimeforadministrationofthe
drugisduringhyperventilationwhenthecarbondioxidelevelofthebloodislow.Itshouldneverbeadministeredin
thepresenceofhighconcentrationsofhalothaneorcyclopropane.Incardiaccasesandseverelyillpatients,itis
advisabletotitratetheexactdoseofProstigminrequired,usingaperipheralnervestimulatordevice.Inthepresence
ofbradycardia,thepulserateshouldbeincreasedtoabout80/minutewithatropinebeforeadministering
Prostigmin.

Tranquilizers/Anticonvulsants
Anumberofdifferentdrugcategoriescanbeusedastranquilizers,includingbarbituratesandbenzodiazepines.
Benzodiazepinederivativesarethechlordiazepoxide,diazepam,oxazepam,clorazepate,lorazepam,prazepam,
alprazolam,andhalazepam.Althoughcommonlyusedfortreatinganxiety,thesedrugsshareothertherapeutic
indicationsnotablysedationandinductionofsleep.
Theeffectsofthebenzodiazepinesinthereliefofanxietyhasbeendemonstratedreadilyinexperimental
animals.Inconflictpunishmentprocedures,benzodiazepinesgreatlyreducethesuppressiveeffectsofpunishment.
Positiveeffectsinthisexperimentalmodelarenotseenwithantidepressantsandantipsychotics.
Incommonwithbarbiturates,benzodiazepinesblockEEGarousalfromstimulationofthebrainstemreticular
formation.Benzodiazepinesexertcentraldepressantactionsonspinalreflexes,inpartmediatedbythebrainstem
reticularsystem.Likemeprobamateandthebarbiturates,chlordiazepoxidedepressesthedurationofelectrical
afterdischargeinthelimbicsystem,includingtheseptalregion,theamygdala,thehippocampus,andthe
hypothalamus.Virtuallyallbenzodiazepineselevateseizurethresholdandareanticonvulsant.Clonazepam,
diazepam,andclorazepateareusedclinicallyforthispurpose.


Thereisalsomuchinterestintheeffectsofbenzodiazepinesonneurotransmissionintheforebrainthatismediated
bygammaaminobutyricacid(GABA).Oneofthemostimportantinhibitoryneurotransmissionsystemsinthebrain
ismediatedbyGABAAreceptorsandClionchannels.Researchonthissystemhasbeenstimulatedby
electrophysiologicalobservationsofthepotentiationoftheinhibitoryeffectsofGABAbybenzodiazepines(aswellas
byalcoholandbarbiturates)andbythediscoveryofspecificbindingsitesforbenzodiazepinesinvariousbrain
regions,particularlycerebellum,cerebralcortex,andthelimbicsystem.Thesesitesarebelievedtooccurinaprotein
macromolecularcomplexthatincludesthelargefamilyofGABAAreceptorsandaClchannel.Bindingof
benzodiazepinescanbemodulatedbybothGABAandClevenafterextensivepurificationofthebindingsites.
Severalimidazolebenzodiazepines,whichactasbenzodiazepineantagonists(e.g.,flumazenilorRo151788),and
carbolinecompoundswithoppositephysiologicalactionstothoseofbenzodiazepines[inverseagonists,including
ethylcarboline3carboxylate(CCE)andits6,7dimethoxycongener(DMCM)]competitivelyinhibitthebinding
ofthebenzodiazepines.Atconcentrationsinthetherapeuticrange,benzodiazepinesalsocanreducetheexcitability
ofsomeneuronsbyactionsthatinvolveneitherGABAnoralterationsinmembranepermeabilitytoCl.Thus,cellular
mechanismsinadditiontotheimportantfacilitationofGABAmediatedClconductancemaycontributetothe
behavioraleffectsofbenzodiazepines.
Thebenzodiazepinesasaclasstendtohaveminimalpharmacokineticinteractionswithotherdrugs,although
theiroxidativemetabolismmaybeinhibitedbycimetidine,disulfiram,isoniazid,andoralcontraceptivesandappears
tobeincreasedbyrifampin.
Diazepam(Valium)
Description:Diazepamisabenzodiazepinederivativeactingonpartsofthelimbicsystem,thalamusand
hypothalamusinducingcalmingeffects.
Usage:Itcanbegivenasananticonvulsant,butbewareofbloodpressurechanges.ItisdistributedasValiumby
RocheProducts.
DosageandAdministration:25mgIMorIV.
Phenytoin
Description:Phenytoinisanantiepilecticdrug.Dilantinisindicatedforthecontroloftonicclonicandpsychomotor
(grandmalandtemporallobe)seizuresandpreventionandtreatmentofseizuresoccurringduringorfollowing
neurosurgery.
Usage:Diazepamistobeusedbeforephenytoin.ItisdistributedasDilantinbyParkeDavis.
DosageandAdministration:50100mgIM510mg/kgslowlyIV.
Phenobarbital
Description:NonselectiveCNSdepressantofthebarbiturateclass,thatproducesdrowsiness,sedation,hypnosis,
andanticonvulsanteffectsbydepressingsensorimotoractivityandcerebellarfunction.Ithasarapidonsetofaction
(about5minutes),withpeakeffectswithin30minutes,andlastsforabout10hours.
Usage:Fordepressingseizureactivityinanimalsthatmaydevelopanimplantinfection,oraminorstrokeasaresult
ofrecordingguidetubeplacement.Ifthemonkeyisinepilepticstatusmultiplythetotalamountdrugby3(i.e.15
mg/kg)andinjectitover1015minutes.Foranticonvulsanttherapyadministerthetotaldailyamountin2doses.
Makesantibioticssuchaschloramphenicollesseffecitve.Ifrespiratorydepressionoccursrespiratethemonkeyusing
ourbagmaskresuscitator(Ambu).Ifdepressionpersistadministerdoxapram.

DosageandAdministration:0.025ml/kg/day

DissociationAnesthetics
Somearylcycloalkylaminesmayinduceastateofsedation,immobility,amnesia,andmarkedanalgesia.Thename
dissociativeanesthesiaisderivedfromthestrongfeelingofdissociationfromtheenvironmentthatisexperiencedby
thesubjecttowhomsuchanagentisadministered.Thisconditionissimilartoneuroleptanalgesiabutresultsfrom
theadministrationofasingledrug.Phencyclidinewasthefirstdrugusedforthispurpose,butthefrequent
occurrenceofunpleasanthallucinationsandpsychologicalproblemssoonledtoitsabandonment.Theseeffectsare
muchlessfrequentwithketaminehydrochloride(2[ochlorophenyl]2[methylamino]cyclohexanonehydrochloride;
Ketalar),whichisavailableforintravenousorintramuscularinjection.
KetamineHydrochloride(Ketalar)
Description:Ketamineisanonnarcotic,nonbarbiturateanestheticwhichproducesadissociativementalstate
characterizedbysedation,amnesiaandanalgesia.Itspharmacologicalactionischaracterizedbyprofoundanalgesia,
normalpharyngeallaryngealreflexes.
EffectsonCNS:TheprimarysiteofCNSactionofketamineappearstobethethalamoneocorticalprojectionsystem.
Itselectivelydepressesneuronalfunctioninpartsofthecortex(especiallyassociationareas)andthalamus,while
simultaneouslystimulatingpartsofthelimbicsystem,includingthehippocampus.Thiscreateswhatistermeda
functionaldisorganizationofnonspecificpathwaysinmidbrainandthalamicareas.Thereisalsoevidencethat
ketaminedepressestransmissionofimpulsesinthemedialmedullaryreticularformation,whichisimportantto
transmissionoftheaffectiveemotionalcomponentsofnociceptionfromthespinalcordtohigherbraincenters.
BlockadeofCNSsodiumchannelshasbeenshownnottobethemechanismofactionbywhichketamineproduces
anesthesia.Thereissomeevidencethatketamineoccupiesopiatereceptorsinthebrainandspinalcord,which
couldaccountforsomeoftheanalgesiceffects.NMethyldaspartate(NMDA)receptorinteractionmaymediatethe
generalanestheticaswellassomeanalgesicactionsofketamine.Thespinalcordanalgesiceffectofketamineis
postulatedtobeduetoinhibitionofdorsalhornwidedynamicrange(WDR)neuronalactivity.Althoughanumberof
drugshavebeenusedtoantagonizeketamine,nospecificreceptorantagonistisyetknownthatreversesalltheCNS
effectsofketamine.Ketamineincreasescerebralmetabolism,CBF,andintracranialpressure(ICP).
EffectsontheRespiratorySystem:Ketaminehasminimaleffectsonthecentralrespiratorydriveasreflectedbyan
unalteredresponsetocarbondioxide.Therecanbeatransient(1to3minute)decreaseinminuteventilationafter
thebolusadministrationofananesthetizingdoseofketamine(2mg/kgIV).Unusuallyhighdosescanproduce
apnea,butthisisseldomseen.Arterialbloodgasesaregenerallypreservedwhenketamineisusedalonefor
anesthesiaoranalgesia.However,withtheuseofadjuvantsedativesoranestheticdrugs,respiratorydepressioncan
occur.Ketaminehasbeenshowntoaffectventilatorycontrolinchildrenandshouldbeconsideredapossible
respiratorydepressantwhengiventotheminbolusdoses.
Ketamineisabronchialsmoothmusclerelaxant.Whenitisgiventopatientswithreactiveairwaydiseaseand
bronchospasm,pulmonarycomplianceisimproved.Ketamineisaseffectiveashalothaneorenfluraneinpreventing
experimentallyinducedbronchospasm.Themechanismforthiseffectisprobablyaresultofthesympathomimetic
responsetoketamine,butthereareisolatedbronchialsmoothmusclestudiesshowingthatketaminecandirectly
antagonizethespasmogeniceffectsofcarbacholandhistamine.Owingtoitsbronchodilatingeffect,ketaminehas
beenusedtotreatstatusasthmaticusunresponsivetoconventionaltherapy.
Apotentialrespiratoryproblemistheincreasedsalivationthatfollowsketamine.Thiscanproduceupperairway
obstruction,whichcanbefurthercomplicatedbylaryngospasm.Theincreasedsecretionsmayalsocontributetoor
furthercomplicatelaryngospasm.Also,althoughswallow,cough,sneeze,andgagreflexesarerelativelyintactafter
ketamine,thereisevidencethatsilentaspirationcanoccurduringketamineanesthesia.

EffectsontheCardiovascularSystem:Ketaminealsohas uniquecardiovasculareffects;itstimulatesthe
cardiovascularsystemandisusuallyassociatedwithincreasesinbloodpressure,heartrate,andcardiacoutput.
Otheranestheticinductiondrugseithercausenochangeinhemodynamicvariablesorproducevasodilationwith
cardiacdepression.Theincreaseinhemodynamicvariablesisassociatedwithincreasedworkandmyocardialoxygen
consumption.Thenormalheartisabletoincreaseoxygensupplybyincreasedcardiacoutputanddecreased
coronaryvascularresistance,sothatcoronarybloodflowisappropriatefortheincreasedoxygenconsumption.The
hemodynamicchangesarenotrelatedtothedoseofketamine(e.g.,thereisnohemodynamicdifferencebetween
administrationof0.5and1.5mg/kgIV).Itisalsointerestingthataseconddoseofketamineproduceshemodynamic
effectslessthanorevenoppositetothoseofthefirstdose.Thehemodynamicchangesafteranesthesiainduction
withketaminetendtobethesameinhealthypatientsandthosewithavarietyofacquiredorcongenitalheart
diseases.Inpatientswithcongenitalheartdisease,therearenosignificantchangesinshuntdirectionsorfractionor
systemicoxygenationafterketamineinductionofanesthesia.Inpatientswhohaveelevatedpulmonaryartery
pressure(aswithmitralvalvularandsomecongenitallesions),ketamineseemstocauseamorepronounced
increaseinpulmonarythaninsystemicvascularresistance.
Themechanismbywhichketaminestimulatesthecirculatorysystemremainsenigmatic.Itappearsnottobea
peripheralmechanismsuchasbaroreflexinhibition,butrathertobecentral.Thereissomeevidencethatketamine
willattenuatebaroreceptorfunctionviaaneffectonNMDAreceptorsinthenucleustractussolitarius.Ketamine
injecteddirectlyintotheCNSproducesanimmediatesympatheticnervoussystemhemodynamicresponse.
Ketaminealsocausesthesympathoneuronalreleaseofnorepinephrine,whichcanbedetectedinvenousblood.
Blockadeofthiseffectispossiblewithbarbiturates,benzodiazepines,anddroperidol.Ketamineinvitroprobablyhas
negativeinotropiceffects.Myocardialdepressionhasbeendemonstratedinisolatedrabbithearts,intactdogs,
chronicallyinstrumenteddogs,andisolatedcanineheartpreparations.However,inisolatedguineapighearts,
ketaminewastheleastdepressantofallthemajorinductiondrugs.Thefactthatketaminemayexertitsmyocardial
effectsbyactinguponmyocardialioniccurrents(whichmayexertdifferenteffectsfromspeciestospeciesoramong
tissuetypes)mayexplainthetissueandanimalmodelvariancesindirectmyocardialaction.
Thecentrallymediatedsympatheticresponsestoketamineusuallyoverridethedirectdepressanteffectsof
ketamine.Therearesomeperipheralnervoussystemactionsofketaminethatplayanundeterminedroleinthe
hemodynamiceffectsofthedrug.Ketamineinhibitsintraneuronaluptakeofcatecholaminesinacocainelikeeffect
andinhibitsextraneuronalnorepinephrineuptake.
Usage:Ketaminecanbeusedasasupplementoradjuncttoregionalanesthesia,extendingtheusefulnessofthe
primary(localanesthetic)formofanesthesia.Inthissettingketaminecanbeusedpriortotheapplicationofpainful
blocks,butmorecommonlyitisusedforsedationorsupplementalanesthesiaduringlongoruncomfortable
procedures.Whenusedforsupplementationofregionalanesthesia,ketamine(0.5mg/kgIV)combinedwith
diazepam(0.15mg/kgIV)isbetteracceptedbyhumanpatientsandnotassociatedwithgreatersideeffectsas
comparedwithunsedatedpatients.
Weuseitmainlyasamildmeansforrestrainingtheanimal(changingcollarsetc.),andforpreparingtheanimal
foranesthesia(placementofthecatheter,oxygenation,induction,etc.).

DosageandAdministration:ItcanbegivenIMorIV.It isdistributedasKetalarbyParkeDavisandasKetasetor
KetajectbyBristolLaboratories.Atropineshouldbeadministeredbeforehand.Itcausesmildrespiratorydepression
andmildcardiacstimulation.Dosagesfordifferentprimatespeciescanbefoundinthefollowingtable.
Species

Restraint(mg/kg)

Preanesthetic(mg/kg)

Aotustrivirgatus(owl)

1012

2025mg/kg

Cebuscapuchin

1315

2530

Cercopithicusaethiops

1012

2530

MacacaFascicullaris.

1215

2025

M.fuscata(japanese)

10

M.mulata(rhesus)

510

2025

M.nemestrina(pigtail)

57.5

1520

M.radiata(bonnet)

1215

2530

M.arctoides(stumptail)

57.5

2025

Saimirisciureus(squirrel)

1215

2530

InhalationAnesthetics
NitrousOxide
Description:Nitrousoxideisprobablythemostcommonsupplementusedwithopioidbasedanesthesia.Nitrous
oxidehasminimaleffectsoncardiovasculardynamics,butstillcandepressmyocardialcontractility.Inaddition,
nitrousoxideincombinationwithopioidsisusuallyassociatedwithsignificantcardiovasculardepression.After
administrationofmorphine(2mg/kg),nitrousoxideproducesconcentrationdependentdecreasesinstrokevolume,
cardiacoutput,andarterialbloodpressureandincreasesinSVR.Whilefentanylaloneproducesnoventricular
dysfunction(eveninthepresenceofsignificantcoronaryarterystenosis),theadditionofnitrousoxidecanresultin
significantcardiovasculardepression.PerhapsalowerFIO2inadditiontonitrousoxidereducescardiovascular
performance.Myocardialischemiaanddysfunctionmayoccurduringinhalationofnitrousoxideascoronaryblood
flowdecreasesasaresultofhypotensionandanincreaseincoronaryvascularresistance.Alternatively,increasesin
SVRassociatedwithnitrousoxidesupplementationofopioidsmayinpartcausethedeteriorationincardiacoutput
andfunction.Otherstudiesdemonstratethatnitrousoxidedoesnotexacerbatemyocardialischemia.Myocardial
dysfunctionwithnitrousoxidemaynotbeevidentwithroutinemonitoring(i.e.,arterialbloodpressure),becauseof
theelevatedSVR.Inspiteofthesepotentialproblems,nitrousoxideremainsapopularsupplement.Nitrousoxide
maybevaluableandsafeasasupplementtoopioidanesthesiainchildrenundergoingrepairofcongenitalcardiac
defects.
Usage:Forallproceduresinwhichcorticalsuppressionmustbeavoided.Itmustalwaysbeusedtogetherwith
analgesics.
DosageandAdministration:Wetypicallyusethisin1lt/minwith1lt/minOxygenflow(50%).
Isoflurane
Description:Isofluraneisthenewestinhalantanestheticavailable.Thevaporpressureofisofluraneresemblesthat
ofhalothanesothatitcanbeadministeredinahalothanetypevaporizer.Isofluranehasthelargestcirculatory
marginofsafetyofallpotenthalogenatedagents.Itproducestheleastmyocardialdepressionatagivenmultipleof
theminimumalveolarconcentration.Inyounganimalsitmayincreaseheartrate,andthusitisoccasionally

associatedwithtachycardia.Similartohalothane,
isofluranedoescauserespiratorydepression,andhence
itshouldbeusedcarefully,withcontinuousmonitoringoftheanimal.Inourprocedures,weusuallyrestrainthe
animalwithKetamine,andweperformtheintubationunderpropofolorbarbiturateanesthesia.Inductionof
surgicalanesthesiaisthereforeaccomplishedwithlowerisofluraneconcentrations.
Isofluranewasthemostslowlymetabolizedofthefluorinatedinhaledanestheticsuntiltherecentintroductionof
desflurane.Whatlittlemetabolismthereisresultsfromoxidationoftheacarbon.Aswithenflurane,the
difluoromethylcarbonofisofluraneisresistanttooxidation.However,tracesoftrifluoroaceticacidmaybeexcreted
intheurineofratsandhumans.Trifluoroacetaldehydeandtrifluoroacetylchloride,expectedintermediatesbetween
isofluraneandtrifluoroaceticacid,mayalsobeproduced.Althoughphenobarbital,phenytoin,ethanol,andisoniazid
pretreatmentsincreasethedefluorinationofisoflurane,enzymeinductionhasnotproducedserumFconcentrations
ofclinicalsignificance.Prolongedexposuretosubanestheticconcentrationsofisofluraneenhancedthehexobarbital
sleepingtimeofrats.Miceexposedtoasmuchas0.5percentisofluranefor4hoursperday,5daysperweekfor9
weekshadnosignificantchangesinhepaticmicrosomalcytochromeP450orb5contentsorindefluorinationrates
ofmethoxyflurane,enflurane,orisoflurane.
Usage:Weuseitforallsurgicalproceduresrequiringgeneralsurgicalanesthesia.
DosageandAdministration:Wetypicallyuse3.5%fora6to8kganimalforabout3minutes,andsubsequently
reducetheconcentrationto1.21.5%.Isofluraneismetabolizedtosuchasmallextentthatanyincreasein
metabolismwouldbeinconsequential(seedetailsinCharlesShort,1987).Thereisgreaterprotectionoftheliver
duringisofluraneanesthesiathanhalothane.Finally,insharpcontrasttohalothane,isofluraneisnonflammable.
Desflurane
Description:Desflurane(SUPRANE)isthenewestvolatileanestheticandhaslowsolubilityinlipidsandblood.
Chemicallyitisthedifluoromethyl1fluoro2,2,2trifluoroethylether.Desfluraneisnonflammable,stableincarbon
dioxide,absorbent,andnoncorrosivetometals.Solubilityinrubberandplasticsisunimportantclinically.Theboiling
pointofdesfluraneisclosetoroomtemperature,anddeliveryofpreciseconcentrationsisachievedbyusinga
specialheatedvaporizertogeneratepurevapor,whichisdilutedappropriatelywithgases(i.e.,oxygenwithor
withoutnitrousoxide).
Althoughthesubstitutionofthechlorineofisofluranewiththefluorineindesfluranereducesthebloodsolubility
tonearthatofnitrousoxide,thepotencyofdesflurane,whichislessthanthatofisoflurane,ismuchgreaterthan
thatofnitrousoxide.Theresultisapreciselycontrolledanestheticwithrapidonsetandrapidrecovery.These
characteristicsareparticularlydesirablefortheexpandingpracticeofoutpatientsurgery.
Atinhaledconcentrationsgreaterthan6%,thepungencyofdesfluranemaycauseirritation,withcoughing,
breathholding,orlaryngospasm.Consequently,anesthesiausuallyisinducedwithanintravenousagent,and
desfluraneisintroducedafterintubationofthetracheatosecuretheairway.Thepropertiesofdesfluranepermit
anesthesiatobeestablishedrapidly.Unlikesituationswithhalothane,isoflurane,orenflurane,thealveolar(or
blood)concentrationofdesfluranewillbe80%ofthatdeliveredfromthevaporizerafteronly5minutes.Conversely,
whendesfluraneisdiscontinued,thesmallbloodandtissuesolubilitycoefficientsensurethattheagentiseliminated
rapidlyintheexhaledgas.Recoveryisapproximatelytwiceasrapidaswithisoflurane,andpatientsareableto
respondtocommandswithin5to10minutesofdiscontinuingdesflurane.
CirculatoryEffects:Thecirculatoryeffectsofdesfluraneresemblethoseofisoflurane.Bloodpressuredecreasesina
dosedependentmanner,mainlybydecreasingsystemicvascularresistance,whilecardiacoutputispreserveduntil
excessivedosesofdesfluraneareadministered.Cardiacratetendstoincrease,particularlyduringinductionor
abruptincreasesindeliveredconcentration.Thismaybeaccompaniedbyanincreaseinsystemicbloodpressure
associatedwithincreasedplasmacatecholamines.However,thesechangesaretransient,and,liketheother
halogenatedethers,desfluranedoesnotpredisposetoventriculararrhythmias.

Thedistributionofsystemicbloodflowisalteredina subtlefashionduringdesfluraneanesthesia.Splanchnic,
renal,cerebral,andcoronarybloodflowsarepreservedintheabsenceofhypotension,whereashepaticbloodflow
maybereduced.Coronaryvasculardilatationleadingtoischemiaasaresultof"coronarysteal"hasnotbeen
observedwithdesfluraneinanimalmodels,anddesfluraneisnotassociatedwithincreasedadverseoutcomesin
patientswithcoronaryarterydisease.
Respiration:.Ventilatorydepressionisprofoundwithdesflurane;inpatientsbreathingspontaneously,thearterial
carbondioxidetensionincreases,andventilationmayceaseataconcentrationof2MAC.Theseandothereffectsof
desfluraneonrespiratoryfunctionaresimilartothoseofothervolatileanesthetics
NervousSystem:Desfluranedecreasescerebralvascularresistanceandcerebralmetabolicrateandisassociated
withanincreaseofintracranialpressure.Autoregulationofcerebralbloodflowismaintained,andbloodflow
remainsresponsivetochangesincarbondioxideconcentration.Theseeffectsofdesfluranearesimilartothoseof
theotheragentsdiscussedpreviously.ChangesinEEGwithdesfluranearesimilartothosewithisoflurane,and
seizurelikeactivityisnotobserved.
Usage:Weuseitforproceduresthatrequireimmediatewakingupoftheanimal.
DosageandAdministration:46%withairor3%withN2O.

IntravenousBarbiturateAnesthetics
Thebarbituratesreversiblydepresstheactivityofallexcitabletissues.TheCNSisexquisitelysensitive,and,even
whenbarbituratesaregiveninanestheticconcentrations,directeffectsonperipheralexcitabletissuesareweak.
However,seriousdeficitsincardiovascularandotherperipheralfunctionsoccurinacutebarbiturateintoxication.
ThebarbituratescanproducealldegreesofdepressionoftheCNS,rangingfrommildsedationtogeneral
anesthesia.Certainbarbiturates,particularlythosecontaininga5phenylsubstituent(phenobarbital,
mephobarbital),haveselectiveanticonvulsantactivity.Theantianxietypropertiesofthebarbituratesarenot
equivalenttothoseexertedbythebenzodiazepines,especiallywithrespecttothedegreeofsedationthatis
produced.Thebarbituratesmayhaveeuphorianteffects.
Exceptfortheanticonvulsantactivitiesofphenobarbitalanditscongeners,thebarbituratespossessalowdegree
ofselectivityandtherapeuticindex.Thus,itisnotpossibletoachieveadesiredeffectwithoutevidenceofgeneral
depressionoftheCNS.Painperceptionandreactionarerelativelyunimpaireduntilthemomentofunconsciousness,
andinsmalldosesthebarbituratesincreasethereactiontopainfulstimuli.Hence,theycannotberelieduponto
producesedationorsleepinthepresenceofevenmoderatepain.Insomeindividualsandinsomecircumstances,
suchasinthepresenceofpain,barbituratescauseovertexcitementinsteadofsedation.Thefactthatsuch
paradoxicalexcitementoccurswithotherCNSdepressantssuggeststhatitmayresultfromdepressionofinhibitory
centers.
Pentobarbital
Description:Pentobarbitalisabarbiturateanesthetic,suppliedasNembutalbyAbbottLaboratories.Itisusedto
provideanesthesiaforlongsurgicalprocedures.Itsdurationofactionrangesfrom3060minutes.Thereisa
tendencytounderdosesmallanimalsandoverdoselargeanimalsinthesamespeciesandagegroupbecausedrug
doseswithinagroupultimatelydependonmetabolicsize.Thisistheanestheticmostcommonlyusedinthis
laboratory.
Usage:Rarelyforgeneralanesthesia.
DosageandAdministration:Nembutal2430mg/kg,butwhenketamineorotherpreanestheticonboard,useabout
1/3to1/6ofit,soeither8mg/kgor4mg/kg.Inductiondosedependsonthedrugsusedtorestraintheanimal.We

typicallyuse8mg/kgasaninductiondose,with4mg/kg givenasmaintenancedoses.Weusethe50mg/ml
concentration.Forthisconcentrationthedosageis0.16ml/kg(forInduction)0.08ml/kg(forMaintenance).
Thiopental
Description:Thiopentalisanultrashortactingthiobarbiturateusedforinductionofanesthesia.Itisdistributedas
PentothalbyAbbottLaboratories.
Respiration:.Unlikesomeoftheinhalationalanesthetics,thiopentalisnotirritatingtotherespiratorytract,andyet
coughing,laryngospasm,andevenbronchospasmoccurwithsomefrequency.Thebasisofthesereactionsis
unknown;theydisappearasadeeperplaneofanesthesiaisestablished.Thepresenceofsaliva,theinsertionofan
airway,orpartialobstructionbysofttissuesmaytriggeroneoralloftheseresponses.Moderatedosesofthiopental
donotdepresstheseairwayreflexes.
Thiopentalproducesadoserelateddepressionofrespirationthatcanbeprofound.Boththeresponsetocarbon
dioxideandtheresponsetohypoxiaarereducedorevenabolished.Followingadoseofthiopentalsufficientto
causesleep,tidalvolumeisdecreased,and,despiteasmallincreaseofrespiratoryrate,theminutevolumeis
reduced;thefunctionalresidualcapacitymaybereduced,especiallyifcoughingoccurs;andthearterialtensionof
carbondioxiderisesslightly.Largerdosesofthiopentalcausemoreprofoundchanges,andrespirationismaintained
onlybymovementsofthediaphragm.Surgicalmanipulationsprovideastimulustorespirationand,withinlimits,can
offsettherespiratorydepression.
Circulation:.Followingtheadministrationofananestheticdoseofthiopentaltoanormaladult,thearterialblood
pressuredecreasesonlytransientlyandthenreturnsessentiallytonormal.Cardiacoutputusuallyisdecreased
somewhat,buttotalperipheralvascularresistanceisunchangedorincreased.Bloodflowtotheskinandbrainis
decreased,butthattootherorgansremainsessentiallynormal.
Inthepresenceofhemorrhageorotherformofhypovolemia,circulatoryinstability,sepsis,toxemia,orshock,
theadministrationofa"normal"doseofthiopentalmayresultinhypotension,circulatorycollapse,andcardiac
arrest.Thiopentaloranyothergeneralanestheticagentshouldbeusedverycautiouslyinpatientswiththese
conditions.Thebaroreceptorsystemappearsunaffectedbythiopental,butsympatheticnerveactivityisreduced.
Concentrationsofcatecholaminesinplasmaarenotincreased,andtheheartisnotsensitizedtoepinephrine.
Arrhythmiasareuncommonexceptinthepresenceofhypercapniaorarterialhypoxemia.
Cerebralbloodflowandcerebralmetabolicratearereducedwiththiopentalandotherbarbiturates.Intracranial
pressureisreducedmarkedly,andthiseffectisutilizedclinicallyinanesthesiaforneurosurgeryorinother
circumstanceswhenelevatedintracranialpressuresareexpected.Dosesofthiopentalsufficienttocausean
isoelectricEEGprotectthebrainduringischemia,butnotifcardiacarrestorheadinjuryhasalreadyrenderedthe
EEGisoelectric.
Usage:Forsingleunitrecordingsistheonlyappropriatebarbituratesincepentobarbitalsuppressescellactivity.
DosageandAdministration:Atotal1520mg/kgIVShouldbegiventoeffect(at30sec.intervals)Startwithathird
toahalfofthecalculateddosage.

IntravenousNonbarbiturateAnesthetics
DiprivanInjection(Propofol)
Description:DiprivanInjectionisanintravenoussedativehypnoticagentforuseintheinductionandmaintenanceof
anesthesiaorsedation.Intravenousinjectionofatherapeuticdoseofpropofolproduceshypnosisrapidlywith
minimalexcitation,usuallywithin40secondsfromthestartofaninjection(thetimeforonearmbraincirculation).
Aswithotherrapidlyactingintravenousanestheticagents,thehalftimeofthebloodbrainequilibrationis
approximately1to3minutes,andthisaccountsfortherapidinductionofanesthesia.

Thepharmacodynamicpropertiesofpropofolare
dependentuponthetherapeuticbloodpropofol
concentrations.Steadystatepropofolbloodconcentrationsaregenerallyproportionaltoinfusionrates,especially
withinanindividualpatient.Undesirablesideeffectssuchascardiorespiratorydepressionarelikelytooccurat
higherbloodconcentrationswhichresultfrombolusdosingorrapidincreaseininfusionrate.Anadequateinterval
(3to5minutes)mustbeallowedbetweenclinicaldosageadjustmentsinordertoassessdrugeffects.The
hemodynamiceffectsofDiprivanInjectionduringinductionofanesthesiavary.Ifspontaneousventilationis
maintained,themajorcardiovasculareffectsarearterialhypotension(sometimesgreaterthana30%decrease)with
littleornochangeinheartrateandnoappreciabledecreaseincardiacoutput.Ifventilationisassistedorcontrolled
(positivepressureventilation),thedegreeandincidenceofdecreaseincardiacoutputareaccentuated.Additionofa
potentopioid(e.g.,fentanyl,sufentanil)whenusedasapremedicantfurtherdecreasescardiacoutputand
respiratorydrive.
IfanesthesiaiscontinuedbyinfusionofDiprivanInjection,thestimulationofendotrachealintubationand
surgerymayreturnarterialpressuretowardsnormal.However,cardiacoutputmayremaindepressed.Comparative
clinicalstudieshaveshownthatthehemodynamiceffectsofDiprivanInjectionduringinductionofanesthesiaare
generallymorepronouncedthanwithotherIVinductionagentstraditionallyusedforthispurpose.During
maintenance,DiprivanInjectioncausesadecreaseinventilationusuallyassociatedwithanincreaseincarbon
dioxidetensionwhichmaybemarkeddependingupontherateofadministrationandotherconcurrentmedications
(e.g.,opioids,sedatives,etc.).
Usage:DiprivanInjectionisanIVanestheticagentthatcanbeusedforbothinductionand/ormaintenanceof
anesthesiaaspartofabalancedanesthetictechniqueforinpatientandoutpatientsurgeryinadultsandinchildren3
yearsofageorolder.
InductionOfGeneralAnesthesia:Monkeysrequire2.5to3.5mg/kgofDiprivanInjectionforinductionwhen
unpremedicatedorwhenlightlypremedicatedwithoralbenzodiazepinesorintramuscularopioids.Aswithother
sedativehypnoticagents,theamountofintravenousopioidand/orbenzodiazepinepremedicationwillinfluencethe
responseofthepatienttoaninductiondoseofDiprivanInjection.Attentionshouldbepaidtominimizepainon
injectionwhenadministeringDiprivanInjectiontoanimals.RapidbolusesofDiprivanInjectionmaybeadministered
ifsmallveinsarepretreatedwithlidocaineorwhenantecubitalorlargerveinsareutilized.DiprivanInjection
administeredinavariablerateinfusionwithnitrousoxide6070%providessatisfactoryanesthesiaformostpediatric
patients3yearsofageorolder,ASAIorII,undergoinggeneralanesthesia.
MaintenanceOfGeneralAnesthesia:MaintenancebyinfusionofDiprivanInjectionatarateof200300
mcgm/kg/minshouldimmediatelyfollowtheinductiondose.Followingthefirsthalfhourofmaintenance,ifclinical
signsoflightanesthesiaarenotpresent,theinfusionrateshouldbedecreased;duringthisperiod,infusionratesof
125150mcgm/kg/minaretypicallyneeded.However,youngerchildren(5yearsorless)mayrequirelarger
maintenanceinfusionratesthanolderchildren.
Precautions:Monkeysshouldbecontinuouslymonitoredforearlysignsofsignificanthypotensionand/or
bradycardia.Treatmentmayincludeincreasingtherateofintravenousfluid,elevationoflowerextremities,useof
pressoragents,oradministrationofatropine.Apneaoftenoccursduringinductionandmaypersistformorethan60
seconds.Ventilatorysupportmayberequired.
AttentionshouldbepaidtominimizepainonadministrationofDiprivanInjection.Transientlocalpaincanbe
minimizedifthelargerveinsoftheforearmorleg(e.g.safenous).Painduringintravenousinjectionmayalsobe
reducedbypriorinjectionofIVlidocaine(1mLofa1%solution).Withlidocainepretreatment,painisminimal
(incidencelessthan10%)andwelltolerated.Venoussequelae(phlebitisorthrombosis)havebeenreportedrarely
(<1%).Intwowellcontrolledclinicalstudiesusingdedicatedintravenouscatheters,noinstancesofvenoussequelae
wereobservedupto14daysfollowinginduction.Intraarterialinjectioninanimalsdidnotinducelocaltissueeffects.
Accidentalintraarterialinjectionhasbeenreportedinhumanpatients,and,otherthanpain,therewerenomajor
sequelae.

Intentionalinjectionintosubcutaneousor
perivasculartissuesofanimalscausedminimaltissue
reaction.Duringthepostmarketingperiod,therehavebeenrarereportsoflocalpain,swelling,blisters,and/or
tissuenecrosisfollowingaccidentalextravasationofDiprivanInjection.Perioperativemyoclonia,rarelyincluding
convulsionsandopisthotonos,hasoccurredintemporalrelationshipincasesinwhichDiprivanInjectionhasbeen
administered.Clinicalfeaturesofanaphylaxis,whichmayincludeangioedema,bronchospasm,erythemaand
hypotension,occurrarelyfollowingDiprivanInjectionadministration,althoughuseofotherdrugsinmostinstances
makestherelationshiptoDiprivanInjectionunclear.
TherehavebeenrarereportsofpulmonaryedemaintemporalrelationshiptotheadministrationofDiprivan
Injection,althoughacausalrelationshipisunknown.DiprivanInjectionhasnovagolyticactivity.Reportsof
bradycardia,asystole,andrarely,cardiacarresthavebeenassociatedwithDiprivanInjection.Theintravenous
administrationofanticholinergicagents(e.g.atropineorglycopyrrolate)shouldbeconsideredtomodifypotential
increasesinvagaltoneduetoconcomitantagents(e.g.,succinylcholine)orsurgicalstimuli.
DrugInteractions:TheinductiondoserequirementsofDiprivanInjectionmaybereducedinpatientswith
intramuscularorintravenouspremedication,particularlywithnarcotics(e.g.,morphine,meperidine,andfentanyl,
etc.)andcombinationsofopioidsandsedatives(e.g.,benzodiazepines,barbiturates,chloralhydrate,droperidol,
etc.).TheseagentsmayincreasetheanestheticorsedativeeffectsofDiprivanInjectionandmayalsoresultinmore
pronounceddecreasesinsystolic,diastolic,andmeanarterialpressuresandcardiacoutput.
DiprivanInjectiondoesnotcauseaclinicallysignificantchangeinonset,intensityordurationofactionofthe
commonlyusedneuromuscularblockingagents(e.g.,succinylcholineandnondepolarizingmusclerelaxants).No
significantadverseinteractionswithcommonlyusedpremedicationsordrugsusedduringanesthesiaorsedation
(includingarangeofmusclerelaxants,inhalationalagents,analgesicagents,andlocalanestheticagents)havebeen
observed.
Ifoverdosageoccurs,DiprivanInjectionadministrationshouldbediscontinuedimmediately.Overdosageislikely
tocausecardiorespiratorydepression.Respiratorydepressionshouldbetreatedbyartificialventilationwithoxygen.
Cardiovasculardepressionmayrequirerepositioningofthepatientbyraisingthepatient'slegs,increasingtheflow
rateofintravenousfluidsandadministeringpressoragentsand/oranticholinergicagents.
DosageAndAdministration:Inductiondoseformonkeys:2.5to3.5mg/kgadministeredover2030seconds.
Infusionformonkeys:125to300mcgm/kg/min(7.5to18mg/kg/h).Whenindicated,initiationofsedationshould
beginat5mcgm/kg/min(0.3mg/kg/h).Theinfusionrateshouldbeincreasedbyincrementsof5to10
mcgm/kg/min(0.3to0.6mg/kg/h)untilthedesiredlevelofsedationisachieved.Aminimumperiodof5minutes
betweenadjustmentsshouldbeallowedforonsetofpeakdrugeffect.Bolusadministrationof10or20mgshould
onlybeusedtorapidlyincreasedepthofsedationinpatientswherehypotensionisnotlikelytooccur
DilutionPriorToAdministration:WhenDiprivanInjectionisdilutedpriortoadministration,itshouldonlybe
dilutedwith5%DextroseInjection,USP,anditshouldnotbedilutedtoaconcentrationlessthan2mg/mLbecauseit
isanemulsion.Indilutedformithasbeenshowntobemorestablewhenincontactwithglassthanwithplastic(95%
potencyafter2hoursofrunninginfusioninplastic).
AdministrationWithOtherFluids:CompatibilityofDiprivanInjectionwiththecoadministrationof
blood/serum/plasmahasnotbeenestablished.DiprivanInjectionhasbeenshowntobecompatiblewhen
administeredwiththefollowingintravenousfluids.

5%DextroseInjection,USP

LactatedRingersInjection,USP

LactatedRingersand5%DextroseInjection

5%Dextroseand0.45%SodiumChlorideInjection,

5%Dextroseand0.2%SodiumChlorideInjection,USP

USP

HandlingProcedures:Parenteraldrugproductsshouldbeinspectedvisuallyforparticulatematterand
discolorationpriortoadministrationwheneversolutionandcontainerpermit.Propofolundergoesoxidative
degradation,inthepresenceofoxygen,andisthereforepackagedundernitrogentoeliminatethisdegradation
path.Storebelow22degC(72degF).Donotstorebelow4degC(40degF).Refrigerationisnotrecommended.
Shakewellbeforeuse.DiprivanInjectionisasterileemulsioncontaining10mg/mLofpropofolsuitablefor
intravenousadministration.Inadditiontotheactivecomponent,propofol,theformulationalsocontainssoybeanoil
(100mg/mL),glycerol(22.5mg/mL)andegglecithin(12mg/mL);withsodiumhydroxidetoadjustpH.Theemulsion
isisotonicandhasapHof78.5.Strictaseptictechniquemustalwaysbemaintainedduringhandling.
Xylazine
Description:Xylazineisanonnarcoticcompoundactingassedativeandanalgesicaswellasamusclerelaxant.
XylazineisdistributedasRompunbyBayvetDivisionofMilesLaboratories.Theprincipalpharmacologicalactivities
develop3to5minafterIVand10to15minafterIMinjection.Itsmajorusefulness,however,iswhencombined
withketamine.Alwayspremedicatewithatropine.Xylazinecancausevomiting.
Usage:WemainlyuseitincombinationwithKetamineforminorprocedures,whichhoweverrequiretheavoidance
ofunwantedanimalmovements.
DosageandAdministration:Dosage0.51.0mg/kgIM.Thecombinationofketamineandxylazineprovideseffect
anesthesiaformoderatedurationprocedures.Thetwosubstancescanbedeliveredfromthesamesyringe.Dosage
0.6mg/kgxylazineand7mg/kgketamine

LocalAnesthetics
Localanestheticspreventthegenerationandtheconductionofthenerveimpulse.Theirprimarysiteofactionisthe
cellmembrane.Conductionblockcanbedemonstratedinsquidgiantaxonsfromwhichtheaxoplasmhasbeen
removed.Localanestheticsblockconductionbydecreasingorpreventingthelargetransientincreaseinthe
permeabilityofexcitablemembranestoNa+thatnormallyisproducedbyaslightdepolarizationofthemembrane.
ThisactionoflocalanestheticsisduetotheirdirectinteractionwithvoltagegatedNa+channels.Astheanesthetic
actionprogressivelydevelopsinanerve,thethresholdforelectricalexcitabilitygraduallyincreases,therateofrise
oftheactionpotentialdeclines,impulseconductionslows,andthesafetyfactorforconductiondecreases;these
factorsdecreasetheprobabilityofpropagationoftheactionpotential,andnerveconductionfails.
InadditiontoNa+channels,localanestheticsalsocanbindtoothermembraneproteins.Inparticular,theycan
blockK+channels.However,sincetheinteractionoflocalanestheticswithK+channelsrequireshigher
concentrationsofdrug,blockadeofconductionisnotaccompaniedbyanylargeorconsistentchangeinresting
membranepotentialduetoblockofK+channels.
Quaternaryanalogsoflocalanestheticsblockconductionwhenappliedinternallytoperfusedgiantaxonsof
squid,buttheyarerelativelyineffectivewhenappliedexternally.Theseobservationssuggestthatthesiteatwhich
localanestheticsact,atleastintheirchargedform,isaccessibleonlyfromtheinnersurfaceofthemembrane.
Therefore,localanestheticsappliedexternallyfirstmustcrossthemembranebeforetheycanexertablocking
action.Althoughavarietyofphysicochemicalmodelshavebeenproposedtoexplainhowlocalanestheticsachieve
conductionblock,itisnowgenerallyacceptedthatthemajormechanismofactionofthesedrugsinvolvestheir
interactionwithoneormorespecificbindingsiteswithintheNa+channel.

Lidocaine
Lidocaineisusedtoproducelocalanesthesiafollowingsubcutaneousinjection.ItisdistributedasXylocainebyAstra
andasLidocainebyElkinsSinn.Dosage0.5%solutionforinfiltrationanesthesia.
Procaine
Procaineisasyntheticlocalanesthetic.Itisreadilyabsorbedfollowingparenteraladministrationandthusdoesnot
longremainatthesiteofinjection.ItissuppliedasNovocainebyWinthropBreon.Dosage0.250.5%forinfiltration
anesthesia,0.52.0%forperipheralnerveblock,and10%forspinalanesthesia.

MuscleRelaxants
Vecuroniumbromide
Description:Norcuron(vecuroniumbromide)forinjectionisanondepolarizingneuromuscularblockingagentof
intermediateduration.Norcuronissuppliedasasterilenonpyrogenicfreezedriedbufferedcakeofveryfine
microscopiccrystallineparticlesforintravenousinjectiononly.Each10mLvialcontains10mgvecuroniumbromide,
20.75mgcitricacidanhydrous,16.25mgsodiumphosphatedibasicanhydrous,97mgmannitol(toadjusttonicity),
sodiumhydroxideand/orphosphoricacidtobufferandadjusttoapHof4.Each20mLvialcontains20mgof
vecuroniumbromide,41.5mgcitricacidanhydrous,32.5mgsodiumphosphatedibasicanhydrous,194mgmannitol
(toadjusttonicity),sodiumhydroxideand/orphosphoricacidtobufferandadjusttoapHof4.
Norcuronactsbycompetingforcholinergicreceptorsatthemotorendplate.Theantagonismtoacetylcholineis
inhibitedandneuromuscularblockisreversedbyacetylcholinesteraseinhibitorssuchasneostigmine,edrophonium,
andpyridostigmine.Norcuronisabout1/3morepotentthanpancuronium;thedurationofneuromuscularblockade
producedbyNorcuronisshorterthanthatofpancuroniumatinitiallyequipotentdoses.
ThetimetoonsetofparalysisdecreasesandthedurationofmaximumeffectincreaseswithincreasingNorcuron
doses.Theuseofaperipheralnervestimulatorisrecommendedinassessingthedegreeofmuscularrelaxationwith
allneuromuscularblockingdrugs.TheED90(doserequiredtoproduce90%suppressionofthemuscletwitch
responsewithbalancedanesthesia)hasaveraged0.057mg/kg(0.049to0.062mg/kginvariousstudies).Aninitial
Norcurondoseof0.08to0.10mg/kggenerallyproducesfirstdepressionoftwitchinapproximately1minute,good
orexcellentintubationconditionswithin2.5to3minutes,andmaximumneuromuscularblockadewithin3to5
minutesofinjectioninmostpatients.Underbalancedanesthesia,thetimetorecoveryto25%ofcontrol(clinical
duration)isapproximately25to40minutesafterinjectionandrecoveryisusually95%completeapproximately45
65minutesafterinjectionofintubatingdose.TheneuromuscularblockingactionofNorcuronisslightlyenhancedin
thepresenceofpotentinhalationanesthetics.IfNorcuronisfirstadministeredmorethan5minutesafterthestart
oftheinhalationofenflurane,isoflurane,orhalothane,orwhensteadystatehasbeenachieved,theintubatingdose
ofNorcuronmaybedecreasedbyapproximately15%.
RepeatedadministrationofmaintenancedosesofNorcuronhaslittleornocumulativeeffectonthedurationof
neuromuscularblockade.Therefore,repeatdosescanbeadministeredatrelativelyregularintervalswithpredictable
results.Afteraninitialdoseof0.08to0.10mg/kgunderbalancedanesthesia,thefirstmaintenancedose(suggested
maintenancedoseis0.010to0.015mg/kg)isgenerallyrequiredwithin25to40minutes;subsequentmaintenance
doses,ifrequired,maybeadministeredatapproximately12to15minuteintervals.Halothaneanesthesiaincreases
theclinicaldurationofthemaintenancedoseonlyslightly.Underenfluraneamaintenancedoseof0.010mg/kgis
approximatelyequalto0.015mg/kgdoseunderbalancedanesthesia.Therecoveryindex(timefrom25%to75%
recovery)isapproximately1525minutesunderbalancedorhalothaneanesthesia.WhenrecoveryfromNorcuron
neuromuscularblockingeffectbegins,itproceedsmorerapidlythanrecoveryfrompancuronium.Oncespontaneous
recoveryhasstarted,theneuromuscularblockproducedbyNorcuronisreadilyreversedwithvarious
anticholinesteraseagents,e.g.pyridostigmine,neostigmine,oredrophoniuminconjunctionwithananticholinergic
agentsuchasatropineorglycopyrrolate.RapidrecoveryisafindingconsistentwithNorcuron'sshortelimination

halflife,althoughtherehavebeenoccasionalreportsof
intensivecare.

prolongedneuromuscularblockadeinpatientsinthe

Unlikeothernondepolarizingskeletalmusclerelaxants,Norcuronhasnoclinicallysignificanteffectson
hemodynamicparameters.Norcuronwillnotcounteractthosehemodynamicchangesorknownsideeffects
producedbyorassociatedwithanestheticagents,otherdrugsorvariousotherfactorsknowntoalter
hemodynamics.Studiesinvolvingroutinehemodynamicmonitoringingoodrisksurgicalpatientsrevealthatthe
administrationofNorcuronindosesuptothreetimesthatneededtoproduceclinicalrelaxation(0.15mg/kg)did
notproduceclinicallysignificantchangesinsystolic,diastolicormeanarterialpressure.Theheartrate,undersimilar
monitoring,remainedunchangedinsomestudiesandwasloweredbyameanofupto8%inotherstudies.Alarge
doseof0.28mg/kgadministeredduringaperiodofnostimulation,whilepatientswerebeingpreparedforcoronary
arterybypassgrafting,wasnotassociatedwithalterationsinratepressureproductorpulmonarycapillarywedge
pressure.Systemicvascularresistancewasloweredslightlyandcardiacoutputwasincreasedinsignificantly.
MalignantHyperthermia:Manydrugsusedinanestheticpracticearesuspectedofbeingcapableoftriggeringa
potentiallyfatalhypermetabolismofskeletalmuscleknownasmalignanthyperthermia.Thereareinsufficientdata
derivedfromscreeninginsusceptibleanimals(swine)toestablishwhetherornotNorcuroniscapableoftriggering
malignanthyperthermia.
AdverseReactions:Themostfrequentadversereactiontonondepolarizingblockingagentsasaclassconsistsof
anextensionofthedrug'spharmacologicalactionbeyondthetimeperiodneeded.Thismayvaryfromskeletal
muscleweaknesstoprofoundandprolongedskeletalmuscleparalysisresultinginrespirationinsufficiencyorapnea.
InadequatereversaloftheneuromuscularblockadeispossiblewithNorcuronaswithallcurariformdrugs.These
adversereactionsaremanagedbymanualormechanicalventilationuntilrecoveryisjudgedadequate.Littleorno
increaseinintensityofblockadeordurationofactionwithNorcuronisnotedfromtheuseofthiobarbiturates,
narcoticanalgesics,nitrousoxide,ordroperidol.
Overdosage:Prolongedtoprofoundextensionsofparalysisand/ormuscleweaknessaswellasmuscleatrophy
havebeenreportedafterlongtermusetosupportmechanicalventilationintheintensivecareunit.The
administrationofNorcuronhasbeenassociatedwithrareinstancesofhypersensitivityreactions(bronchospasm,
hypotensionand/ortachycardia,sometimesassociatedwithacuteurticariaorerythema).
Thepossibilityofiatrogenicoverdosagecanbeminimizedbycarefullymonitoringmuscletwitchresponseto
peripheralnervestimulation.ExcessivedosesofNorcuronproducedenhancedpharmacologicaleffects.Residual
neuromuscularblockadebeyondthetimeperiodneededmayoccurwithNorcuronaswithotherneuromuscular
blockers.Thismaybemanifestedbyskeletalmuscleweakness,decreasedrespiratoryreserve,lowtidalvolume,or
apnea.Aperipheralnervestimulatormaybeusedtoassessthedegreeofresidualneuromuscularblockadefrom
othercausesofdecreasedrespiratoryreserve.
Respiratorydepressionmaybedueeitherwhollyorinparttootherdrugsusedduringtheconductofgeneral
anesthesiasuchasnarcotics,thiobarbituratesandothercentralnervoussystemdepressants.Undersuch
circumstancestheprimarytreatmentismaintenanceofapatentairwayandmanualormechanicalventilationuntil
completerecoveryofnormalrespirationisassured.Regonol(pyridostigminebromide)injection,neostigmine,or
edrophonium,inconjunctionwithatropineorglycopyrrolatewillusuallyantagonizetheskeletalmusclerelaxant
actionofNorcuron.Satisfactoryreversalcanbejudgedbyadequacyofskeletalmuscletoneandbyadequacyof
respiration.Aperipheralnervestimulatormayalsobeusedtomonitorrestorationoftwitchheight.Failureof
promptreversal(within30minutes)mayoccurinthepresenceofextremedebilitation,carcinomatosis,andwith
concomitantuseofcertainbroadspectrumantibiotics,oranestheticagentsandotherdrugswhichenhance
neuromuscularblockadeorcauserespiratorydepressionoftheirown.Undersuchcircumstancesthemanagementis
thesameasthatofprolongedneuromuscularblockade.Ventilationmustbesupportedbyartificialmeansuntilthe
patienthasresumedcontrolofhisrespiration.Priortotheuseofreversalagents,referenceshouldbemadetothe
specificpackageinsertofthereversalagent.

Usage:Usedformusclerelationsinneurophysiology

experimentsandsomeoftheMRIexperiments.

DosageandAdministration:Norcuron(vecuroniumbromide)forinjectionisforintravenoususeonly.Toobtain
maximumclinicalbenefitsofNorcuronandtominimizethepossibilityofoverdosage,themonitoringofmuscle
twitchresponsetoperipheralnervestimulationisadvised.TherecommendedinitialdoseofNorcuronis0.08to
0.10mg/kg(1.4to1.75timestheED90)givenasanintravenousbolusinjection.Thisdosecanbeexpectedto
producegoodorexcellentnonemergencyintubationconditionsin2.5to3minutesafterinjection.Underbalanced
anesthesia,clinicallyrequiredneuromuscularblockadelastsapproximately2530minutes,withrecoveryto25%of
controlachievedapproximately25to40minutesafterinjectionandrecoveryto95%ofcontrolachieved
approximately4565minutesafterinjection.Inthepresenceofpotentinhalationanesthetics,theneuromuscular
blockingeffectofNorcuronisenhanced.IfNorcuronisfirstadministeredmorethan5minutesafterthestartof
inhalationagentorwhensteadystatehasbeenachieved,theinitialNorcurondosemaybereducedby
approximately15%,i.e.,0.060to0.085mg/kg.
Duringprolongedsurgicalprocedures,maintenancedosesof0.010to0.015mg/kgofNorcuronare
recommended;aftertheinitialNorcuroninjection,thefirstmaintenancedosewillgenerallyberequiredwithin25to
40minutes.However,clinicalcriteriashouldbeusedtodeterminetheneedformaintenancedoses.
SinceNorcuronlacksclinicallyimportantcumulativeeffects,subsequentmaintenancedoses,ifrequired,maybe
administeredatrelativelyregularintervalsforeachpatient,rangingapproximatelyfrom12to15minutesunder
balancedanesthesia,slightlylongerunderinhalationagents.(Iflessfrequentadministrationisdesired,higher
maintenancedosesmaybeadministered.)Shouldtherebereasonfortheselectionoflargerdosesinindividual
patients,initialdosesrangingfrom0.15mg/kgupto0.28mg/kghavebeenadministeredduringsurgeryunder
halothaneanesthesiawithoutilleffectstothecardiovascularsystembeingnotedaslongasventilationisproperly
maintained.
UseByContinuousInfusion:Afteranintubatingdoseof80100mcgm/kg,acontinuousinfusionof1
mcgm/kg/mincanbeinitiatedapproximately2040minlater.InfusionofNorcuronshouldbeinitiatedonlyafter
earlyevidenceofspontaneousrecoveryfromthebolusdose.Longtermintravenousinfusiontosupportmechanical
ventilationintheintensivecareunithasnotbeenstudiedsufficientlytosupportdosagerecommendations.The
infusionofNorcuronshouldbeindividualizedforeachpatient.Therateofadministrationshouldbeadjusted
accordingtothepatient'stwitchresponseasdeterminedbyperipheralnervestimulation.Aninitialrateof1
mcgm/kg/minisrecommended,withtherateoftheinfusionadjustedthereaftertomaintaina90%suppressionof
twitchresponse.Averageinfusionratesmayrangefrom0.8to1.2mcgm/kg/min.
Inhalationanesthetics,particularlyenfluraneandisofluranemayenhancetheneuromuscularblockingactionof
nondepolarizingmusclerelaxants.Inthepresenceofsteadystateconcentrationsofenfluraneorisoflurane,itmay
benecessarytoreducetherateofinfusion2560percent,4560minaftertheintubatingdose.Underhalothane
anesthesiaitmaynotbenecessarytoreducetherateofinfusion.InfusionsolutionsofNorcuroncanbepreparedby
mixingNorcuronwithanappropriateinfusionsolutionsuchas5%glucoseinwater,0.9%NaCl,5%glucoseinsaline,
orLactatedRingers.Unusedportionsofinfusionsolutionsshouldbediscarded.
Compatibility:Norcuroniscompatibleinsolutionwith:0.9%NaClsolution,5%glucoseinwaterSterilewaterfor
injection5%glucoseinsaline,LactatedRingers,Usewithin24hoursofmixingwiththeabovesolutions.Parenteral
drugproductsshouldbeinspectedvisuallyforparticulatematteranddiscolorationpriortoadministrationwhenever
solutionandcontainerpermit.

OpioidAnalgesicsandAntiOpioids
Opioiddrugsareusedprimarilyforthetreatmentofpain.SomeoftheCNSmechanismsthatreducetheperception
ofpainalsoproduceastateofwellbeingoreuphoria.Thus,opioiddrugsalsoaretakenoutsideofmedicalchannels
forthepurposeofobtainingtheeffectsonmood.Thispotentialforabusehasgenerated


muchresearchonseparatingthemechanismofanalgesiafromthatofeuphoriainthehopeofeventuallydeveloping
apotentanalgesicthatdoesnotproduceeuphoria.Althoughthisresearchhasledtoadvancesinunderstandingthe
physiologyofpain,thestandardmedicationsforseverepainremainthederivativesoftheopiumpoppy(opiates)
andsyntheticdrugsthatactivatethesamereceptors(opioids).Drugsmodeledaftertheendogenousopioidpeptides
mayonedayprovidemorespecifictreatment,butnoneofthesecurrentlyisavailableforclinicaluse.Medications
thatdonotactatopiatereceptors,suchasthenonsteroidalantiinflammatorydrugs,haveanimportantrolein
certaintypesofpain,especiallychronicpain;butforacutepainandforseverechronicpain,theagonistopioid
drugsarethemosteffective.Potentialfuturetreatmentsmayincludepreventingthedevelopmentofopioid
toleranceusingNMDAreceptorantagonists.
Themostcommonuseofopioiddrugsisforthetreatmentofacutepain.Somepatientsinpainliketherelaxing,
anxiolytic,euphorigenicpropertiesofopioidsasmuchasthereliefofpain.Thisisparticularlytrueinhighanxiety
situations,suchasthecrushingchestpainofamyocardialinfarction.Normalvolunteerswithnopaingivenopioids
inthelaboratorymayreporttheeffectsasunpleasantbecauseofthesideeffectssuchasnausea,vomiting,and
sedation.Patientswithpainrarelydevelopabuseoraddictionproblems.Ofcourse,patientsreceivingopioids
developtoleranceroutinely,andifthemedicationisstoppedabruptly,theywillshowthesignsofanopioid
withdrawalsyndrome,theevidenceforphysicaldependence.
Themajorriskforabuseoraddictionoccursinpatientscomplainingofpainwithnoclearphysicalexplanationor
withevidenceofachronicdisorderthatisnotlifethreatening.Examplesarechronicheadaches,backaches,
abdominalpain,orperipheralneuropathy.Eveninthesecases,anopioidmightbeconsideredasabriefemergency
treatment,butlongtermtreatmentwithopioidsisnotadvisable.Inthoserelativelyrarepatientswhodevelop
abuse,thetransitionfromlegitimateusetoabuseoftenbeginswithpatientsreturningtotheirphysicianearlierthan
scheduledtogetanewprescriptionorvisitingemergencyroomsofdifferenthospitalscomplainingofacutepainand
askingforanopioidinjection.
MechanismsandSitesofOpioidInducedAnalgesia:Opioidinducedanalgesiaisduetoactionsatseveralsiteswithin
theCNS;bothspinalandmultiplesupraspinalsiteshavebeenidentified.Morphineandothermopioidagonists
selectivelyinhibitvariousnociceptivereflexesandinduceprofoundanalgesiawhenadministeredintrathecallyor
instilledlocallyintothedorsalhornofthespinalcord;othersensorymodalities(e.g.,touch)usuallyareunaffected.
Atleastthreemechanismsappeartobeinvolved.Opioidreceptorsontheterminalsofprimaryafferentnerves
mediateinhibitionofthereleaseofneurotransmitters,includingsubstanceP.Morphinealsoantagonizestheeffects
ofexogenouslyadministeredsubstancePbyexertingpostsynapticinhibitoryactionsoninterneuronsandonthe
outputneuronsofthespinothalamictractthatconveysnociceptiveinformationtohighercentersinthebrain.Both
dandkagonistsappeartoactsimilarly;however,kagonistssuppressnoxiousthermalstimulionlyslightly,andtheir
maximaleffectsonvisceralpainaredistinctlylower.
Profoundanalgesiaalsocanbeproducedbytheinstillationofmorphineintothethirdventricleorinvarioussites
inthemidbrainandmedulla,mostnotablytheperiaqueductalgraymatter,thenucleusraphemagnus,andthelocus
ceruleus.Eitherelectricalorchemicalstimulationatthesesitesalsoinducesanalgesiathatisantagonizedby
naloxone,suggestingmediationbyendogenousopioidpeptides.Althoughthecircuitryhasnotbeenclearlydefined,
allofthesemaneuversresultinenhancedactivityindescendingaminergicbulbospinalpathwaysthatexert
inhibitoryeffectsontheprocessingofnociceptiveinformationinthespinalcord.Analgesiaduetodopioidreceptors
ismediatedspinallythroughthedorsalhorn.Althoughddrugsalsoareanalgesicsupraspinallyinanimalmodels,the
sitesofactionhavenotbeenidentified.Animalmodelssuggestthatagonistsatk1receptorsmediateanalgesia
spinally,whileagonistsatk3receptorsactsupraspinally.
Simultaneousadministrationofmorphineatbothspinalandsupraspinalsitesresultsinsynergyinanalgesic
response,withatenfoldreductioninthetotaldoseofmorphinenecessarytoproduceequivalentanalgesiaateither


sitealone.Themechanismsresponsibleforspinal/supraspinalsynergyarereadilydistinguishedfromthoseinvolved
withsupraspinalanalgesia.Inadditiontothewelldescribedspinal/supraspinalsynergy,synergisticm/mandm/d
receptorinteractionsalsohavebeenobservedwithinthebrainstembetweentheperiaqueductalgray,locus
ceruleus,andnucleusraphemagnus.
MechanismofOtherCNSEffects:Highdosesofopioidscanproducemuscularrigidityinhumanbeings.Chestwall
rigiditysevereenoughtocompromiserespirationisnotuncommonduringanesthesiawithfentanyl,alfentanil,and
sufentanil.Opioidsandendogenouspeptidescausecatalepsy,circling,andstereotypicalbehaviorinratsandother
animals.
Themechanismbywhichopioidsproduceeuphoria,tranquility,andotheralterationsofmoodisnotentirely
clear.Microinjectionofmopioidsintotheventraltegmentumactivatesdopaminergicneuronsthatprojecttothe
nucleusaccumbens;thispathwayispostulatedtobeacriticalelementinthereinforcingeffectsofopioidsand,by
inference,opioidinducedeuphoria.Animalswillworktoreceivesuchinjectionsorinjectionsintothenucleus
accumbensitselforitsprojectionareas.Theadministrationofdopaminergicantagonistsdoesnotconsistently
preventthereinforcingeffectsofopioids,suggestingthatsomenondopaminergicmechanismsmayalsoplayarole.
Theneuralsystemsthatmediateopioidreinforcementintheventraltegmentumappeartobedistinctfromthose
involvedintheclassicalmanifestationsofphysicaldependenceandanalgesia.Theactivationofdreceptorsalsomay
producereinforcingeffects.Incontrasttomagonists,kagonistsinhibitthefiringofdopaminecontainingcellsinthe
substantianigraandinhibitdopaminereleasefromcorticalandstriatalneurons.Asmentionedabove,theyproduce
dysphoriceffectsratherthaneuphoria.Thelocusceruleuscontainsbothnoradrenergicneuronsandhigh
concentrationsofopioidreceptorsandispostulatedtoplayacriticalroleinfeelingsofalarm,panic,fear,and
anxiety.Activityinthelocusceruleusisinhibitedbybothexogenousopioidsandendogenousopioidlikepeptides.
EffectsontheHypothalamus:Opioidsaltertheequilibriumpointofthehypothalamicheatregulatorymechanisms,
suchthatbodytemperatureusuallyfallsslightly.However,chronichighdosagemayincreasebodytemperature.
Miosis:Morphineandmostmandkagonistscauseconstrictionofthepupilbyanexcitatoryactiononthe
parasympatheticnerveinnervatingthepupil.Followingtoxicdosesofmagonists,themiosisismarkedandpinpoint
pupilsarepathognomonic;however,markedmydriasisoccurswhenasphyxiaintervenes.Sometolerancetothe
mioticeffectdevelops,butaddictswithhighcirculatingconcentrationsofopioidscontinuetohaveconstricted
pupils.Therapeuticdosesofmorphineincreaseaccommodativepowerandlowerintraoculartensioninbothnormal
andglaucomatouseyes.
Convulsions:Inanimals,highdosesofmorphineandrelatedopioidsproduceconvulsions.Severalmechanisms
appeartobeinvolved,anddifferenttypesofopioidsproduceseizureswithdifferentcharacteristics.Morphinelike
drugsexcitecertaingroupsofneurons,especiallyhippocampalpyramidalcells;theseexcitatoryeffectsprobably
resultfrominhibitionofthereleaseofgammaaminobutyricacid(GABA)byinterneurons.Selectivedagonists
producesimilareffects.Theseactionsmaycontributetotheseizuresthatareproducedbysomeagentsatdoses
onlymoderatelyhigherthanthoserequiredforanalgesia,especiallyinchildren.However,withmostopioids,
convulsionsoccuronlyatdosesfarinexcessofthoserequiredtoproduceprofoundanalgesia,andseizuresarenot
seenwhenpotentmagonistsareusedtoproduceanesthesia.
Naloxoneismorepotentinantagonizingconvulsionsproducedbysomeopioids(e.g.,morphine,methadone,and
dpropoxyphene)thanthoseproducedbyothers(e.g.,meperidine).Theproductionofconvulsantmetabolitesofthe
latteragentmaybepartiallyresponsible(seebelow).Anticonvulsantagentsmaynotalwaysbeeffectivein
suppressingopioidinducedseizures.
Respiration:Morphinelikeopioidsdepressrespiration,atleastinpartbyvirtueofadirecteffectonthebrainstem
respiratorycenters.Therespiratorydepressionisdiscernibleevenwithdosestoosmalltodisturbconsciousnessand


increasesprogressivelyasthedoseisincreased.Inhumanbeings,deathfrommorphinepoisoningisnearlyalways
duetorespiratoryarrest.Therapeuticdosesofmorphineinhumanbeingsdepressallphasesofrespiratoryactivity
(rate,minutevolume,andtidalexchange)andmayalsoproduceirregularandperiodicbreathing.Thediminished
respiratoryvolumeisdueprimarilytoaslowerrateofbreathing,andwithtoxicamountstheratemayfallto3or4
breathsperminute.Althoughrespiratoryeffectscanbedocumentedreadilywithstandarddosesofmorphine,
respiratorydepressionisrarelyaproblemclinicallyintheabsenceofunderlyingpulmonarydysfunction.However,
thecombinationofopiateswithothermedications,suchasgeneralanesthetics,tranquilizers,alcohol,orsedative
hypnotics,maypresentagreaterriskofrespiratorydepression.
Maximalrespiratorydepressionoccurswithin5to10minutesafterintravenousadministrationofmorphineor
within30or90minutesfollowingintramuscularorsubcutaneousadministration,respectively.Maximaldepressant
effectsoccurmorerapidlywithmorelipidsolubleagents.Followingtherapeuticdoses,respiratoryminutevolume
maybereducedforaslongas4to5hours.Theprimarymechanismofrespiratorydepressionbyopioidsinvolvesa
reductionintheresponsivenessofthebrainstemrespiratorycenterstocarbondioxide.Opioidsalsodepressthe
pontineandmedullarycentersinvolvedinregulatingrespiratoryrhythmicityandtheresponsivenessofmedullary
respiratorycenterstoelectricalstimulation.Hypoxicstimulationofthechemoreceptorsstillmaybeeffectivewhen
opioidshavedecreasedtheresponsivenesstoCO2,andtheinhalationofO2maythusproduceapnea.Afterlarge
dosesofmorphineorothermagonists,patientswillbreatheifinstructedtodoso,butwithoutsuchinstructionthey
mayremainrelativelyapneic.
BecauseoftheaccumulationofCO2,respiratoryrateandsometimesevenminutevolumecanbeunreliable
indicatorsofthedegreeofrespiratorydepressionthathasbeenproducedbymorphine.Naturalsleepalsoproduces
adecreaseinthesensitivityofthemedullarycentertoCO2,andtheeffectsofmorphineandsleepareadditive.
Numerousstudieshavecomparedmorphineandmorphinelikeopioidswithrespecttotheirratiosofanalgesicto
respiratorydepressantactivities.Moststudieshavefoundthat,whenequianalgesicdosesareused,thedegreeof
respiratorydepressionobservedwithmorphinelikeopioidsisnotsignificantlydifferentfromthatseenwith
morphine.However,thepartialagonistandagonist/antagonistopioidsarelesslikelytocausesevererespiratory
depressionandarefarlesscommonlyassociatedwithdeathcausedbyoverdosage.
Highconcentrationsofopioidreceptors,aswellasofendogenouspeptides,arefoundinthemedullaryareas
believedtobeimportantinventilatorycontrol.Asmentionedpreviously,respiratorydepressionmaybemediated
byasubpopulationofmreceptors(m2),distinctfromthosethatareinvolvedintheproductionofsupraspinal
analgesia(m1).Severerespiratorydepressionislesslikelyaftertheadministrationoflargedosesofselectivek
agonists.
NauseantandEmeticEffects:Nauseaandvomitingproducedbymorphinelikedrugsareunpleasantsideeffects
causedbydirectstimulationofthechemoreceptortriggerzoneforemesis,intheareapostremaofthemedulla.
Certainindividualsnevervomitaftermorphine,whereasothersdosoeachtimethedrugisadministered.Nausea
andvomitingarerelativelyuncommoninrecumbentpatientsgiventherapeuticdosesofmorphine,butnausea
occursinapproximately40%andvomitingin15%ofambulatorypatientsgiven15mgofthedrugsubcutaneously.
Thissuggeststhatavestibularcomponentalsoisoperative.Indeed,thenauseantandemeticeffectsofmorphine
aremarkedlyenhancedbyvestibularstimulation,andmorphineandrelatedsyntheticanalgesicsproducean
increaseinvestibularsensitivity.Allclinicallyusefulmagonistsproducesomedegreeofnauseaandvomiting.
Careful,controlledclinicalstudiesusuallydemonstratethat,inequianalgesicdosage,theincidenceofsuchside
effectsisnotsignificantlylowerthanthatseenwithmorphine.Drugsthatareusefulinmotionsicknessare
sometimeshelpfulinreducingopioidinducednauseainambulatorypatients;phenothiazinesarealsouseful.

Fentanyl
Description:Fentanylisanopioidanalgesic.Fentanylinteractspredominatelywiththeopioidmureceptor.These
mubindingsitesarediscretelydistributedinthehumanbrain,spinalcord,andothertissues.Inclinicalsettings,
fentanylexertsitsprincipalpharmacologiceffectsonthecentralnervoussystem.Itsprimaryactionsoftherapeutic
valueareanalgesiaandsedation.Fentanylmayincreasethepatient'stoleranceforpainanddecreasetheperception
ofsuffering,althoughthepresenceofthepainitselfmaystillberecognized.
Inadditiontoanalgesia,alterationsinmood,euphoriaanddysphoria,anddrowsinesscommonlyoccur.Fentanyl
depressestherespiratorycenters,depressesthecoughreflex,andconstrictsthepupils.Analgesicbloodlevelsof
fentanylmaycausenauseaandvomitingdirectlybystimulatingthechemoreceptortriggerzone,butnauseaand
vomitingaresignificantlymorecommoninambulatorythaninrecumbentpatients,asisposturalsyncope.
Opioidsincreasethetoneanddecreasethepropulsivecontractionsofthesmoothmuscleofthegastrointestinal
tract.Theresultantprolongationingastrointestinaltransittimemayberesponsiblefortheconstipatingeffectof
fentanyl.Becauseopioidsmayincreasebiliarytractpressure,somepatientswithbiliarycolicmayexperience
worseningratherthanreliefofpain.Whileopioidsgenerallyincreasethetoneofurinarytractsmoothmuscle,the
neteffecttendstobevariable,insomecasesproducingurinaryurgency,inothers,difficultyinurination.At
therapeuticdosages,fentanylusuallydoesnotexertmajoreffectsonthecardiovascularsystem.However,some
patientsmayexhibitorthostatichypotensionandfainting.Histamineassaysandskinwhealtestinginmanindicate
thatclinicallysignificanthistaminereleaserarelyoccurswithfentanyladministration.Assaysinmanshowno
clinicallysignificanthistaminereleaseindosagesupto50mcgm/kg.
Fentanyl,insmall(2to5mg/kg)oranesthetic(10to100mg/kg)doses,infrequentlycausessignificantdecreases
inarterialbloodpressurewhengivenalone,eveninpatientswithpoorleftventricularfunction(LVF).Mostevidence
indicatesthatfentanylproduceslittleornochangeinmyocardialcontractility,althoughafewinvestigatorshave
reportedanegativeinotropiceffect.Virtuallyallhemodynamicvariables,includingheartrate,arterialblood
pressure,cardiacoutput,systemicandpulmonaryvascularresistance,andpulmonaryarteryocclusionorwedge
pressure,remainunchangedafterlarge(anesthetic)dosesoffentanyl.
Anestheticinductionwithfentanylisassociatedwiththeleastchangeinmeanarterialpressureandmyocardial
performance.Whilesufentanildoesnotproducehemodynamicinstability,itdoescausemyocardialdepression.
Perhapsfentanylispreferredoversufentanilinpatientswithpoorleftventricularfunction.Ontheotherhand,other
investigatorshavefoundbetterhemodynamicstability,lesshypotension,andlessventricularstrokeworkafter
sufentanilthanafterfentanylinpatientsundergoingvalvularheartsurgery.
Hypotensionafterfentanylisoftenrelatedtoassociatedbradycardiaandcanbepreventedortreatedwith
anticholinergics,ephedrine,orevenpancuronium.Patientswithhighsympathetictonearemorelikelytoexperience
hypotensionafterfentanyl.
Usage:Usedinsurgicalprocedureasperioperativeanalgesic.
DosageandAdministration:Fentanylis100timesmorepotentthanmorphine.Theonsetofthedrugisimmediate
whenitisgivenIVandthedurationofactionis30to60minafterasingleIVdoseof100micrograms.FollowingIM
injectiontheonsetis7to8minandthedurationis1to2hr.ItisdistributedasSublimazebyJanssen
Pharmaceutica.Dosage0.050.15milligram/kgIMorSQ.
Sufentanil
Sufentanil,whichis7to10timesaspotentasfentanyl,causeshypotensionwithequalorgreaterfrequencyas
comparedwiththelatter.Sincesufentanilisavailableinconcentrationssimilartothoseoffentanyl(50mg/ml)one
obviouspossiblecauseofhypotensionisrelativeoverdose.Sufentanildoesnotproduceincreasesinplasma
histaminebutdoescausevagalinducedbradycardia.Aswithfentanyl,mildtonodepressionofcardiacindexand

pumpfunctionisusuallyobservedaftersufentanilin
humans.Ablationofsympathetictoneandenhanced
parasympathetictonearethemostlikelymechanismsforsufentanilassociatedhypotension.Sufentanilinduced
hypotensionmayalsobemediatedbyadirectdepressionofvascularsmoothmuscle.
Severalstudiessuggestthatsufentanilnotonlyismorepotentthanfentanylbutalsoisclosertoa"complete
anesthetic."TheseclaimsaresupportedbygreaterMACreductionduringcoadministrationofinhalationanesthetics
inlaboratoryanimalsandlesshemodynamicresponsestostimulisuchasintubationinhumans180ascompared
withfentanyl.Sufentanilcancausemorehypotensionthanequipotentdosesoffentanyl.Itisfoundthatsufentanil
(5mg/kg)produceslowermeanarterialbloodpressuresthanfentanyl(25mg/kg)duringinductionofanesthesiain
patientsundergoingcoronaryarterysurgery.Ithasbeenalsoshownthatalthoughsufentanil(15mg/kg)attenuated
thehemodynamicresponsetoendotrachealintubationbetterthanfentanyl(75mg/kg),itimpairedmyocardial
functionanddepressedsystolicbloodpressuremore.
Usage:Analgesicusedduringandaftersurgicalprocedures.
DosageandAdministration:.Dosage8ug/kg.
Buprenorphine
Description:DistributedasBuprenex.Durationofactionis812hours.Peakactionat3hours.Sideeffectsinclude
respiratorydepression,whichwillmanifestitselfasagradualslowingofbreathingandincreasedintracranial
pressure.Buprenorphineisathebainederivative,whichissimilartomorphineinstructurebutapproximately33
timesaspotent.Buprenorphineisapartialmureceptoragonistandalsobindstodeltaandkappareceptors,butits
activityatthelattertwositesisrelativelyinsignificant.91Althoughbuprenorphineishighlylipophilic,itsopiate
receptorassociationanddissociationareslow.Whereasfentanyldisassociatesrapidlyfrommureceptors(t6.8
minutes),buprenorphine,whichhasahigheraffinity,takesmuchlonger(t166minutes).Thus,plasmalevelsdo
notparallelCNSeffects.Buprenorphine'sonsetofactionisslow,anditspeakeffectmaynotoccuruntil3hours,and
thedurationofitseffectisprolonged(upto10hours).Metabolismoccursintheliver,withbiliaryexcretionofmost
metabolites.Themetabolitesofbuprenorphone,buprenorphone3glucuronide,andnorbuprenorphineare
significantlylesspotentandhaveloweraffinitiesforthemureceptor.Theiraccumulationinpatientswithrenal
failureisunlikelytocausesignificantpharmacologicactivity.Buprenorphine'svolumeofdistributionis2.8L/kgand
itsclearanceis20ml/kg/min.Therecommendedinitialanalgesicdoseis0.3to0.4mg.
Thesubjectiveeffects(e.g.,euphoria)ofbuprenorphinearesimilartothoseofmorphine,althoughtheyoccur
lessfrequently.Nauseaandvomitingarethemostcommonsideeffects.Buprenorphineproducesrespiratory
depression,withaceilingafter0.15to1.2mginadults.Higherdosesdonotproducefurtherrespiratorydepression
andmayactuallyresultinincreasedventilation(predominanceofantagonisticactions).Nonetheless,atsomedoses
respiratorydepressionisimpressiveafterbuprenorphine.Reversalwithnaloxoneislimitedowingto
buprenorphine'shighaffinityforandslowdissociationfromthemuopiaterecovery;verylargedosesofnaloxone
and/ordoxaprammayberequiredforfullreversal.Buprenorphine(0.6mgIV)reversestroublesomefentanyl
inducedpostoperativerespiratorydepressionaswellasdoesnaloxone(0.4mg)andbetterpreservesanalgesia.
DopramshouldbeadministeredifNarcandoesnotreversetherespiratorydepression.
Buprenorphinehasbeensuccessfullyusedforpremedication(0.3mgIM),astheanalgesiccomponentin
balancedanesthesia(4.5to12mg/kg),771andforpostoperativepaincontrol(0.3mgIM).Sublingualadministration
(0.4mg)hasalsoprovedeffective.Liketheotheragonistantagonistcompounds,buprenorphineisnotacceptableas
asoleanesthetic,anditsreceptorkineticprofilerestrictsitsusefulnessifothermureceptoragonistsareused
concurrently.Ontheotherhand,inlargedosesbuprenorphinemightbeofvalueasanalternativetomethadonefor
maintenancetherapyinopiateaddicts.Thehemodynamiceffectsofbuprenorphinearesimilartothoseof
morphine.Opioidwithdrawalsymptomsdevelopslowly(5to10days)afterbuprenorphineisdiscontinuedfollowing
chronicuse.Incontrasttootheropioidcompounds(antagonists,agonists,andagonistantagonists)buprenorphine
producesminimaleffectsinmethadonemaintainedopioidabusers.

Usage:Analgesicusedduringandaftersurgical

procedures.

DosageandAdministration:0.010.03mg/kgIMorSCevery812hrs.
Naloxone
Description:Narcan,anarcoticantagonist,isasyntheticcongenerofoxymorphone.Itantagonizestheopioideffects
bycompetingforthesamereceptorsites.thusreversingnarcoticdepressionresultingfromopioidoverdose.Its
durationofactionisapproximately4hours;therefore,itmayneedtobeadministeredmorethanonce.Itis
distributedasNarcanbyDuPont.WhenusingNarcanagainstBuprenexyoumayneedtouse10Xthenormaldose
Usage:Toreversetheeffectsofpossibleoverdoseofnarcotics.NotethatNaloxoneisnoteffectiveagainst
respiratorydepressionduetononopioiddrugs.Reversalofbuprenorphineinducedrespiratorydepressionmaybe
incomplete.Ifanincompleteresponseoccurs,respirationsshouldbemechanicallyassistedusingAMBU.
DosageandAdministration:.Dosage0.010.05mg/kgIMorIVWeusuallyusethe0.4mg/kgconcentration.For
thisconcentrationandforanaveragedosageof0.03mg/kgthedosageis:0.075ml/kg.

NonOpioidAnalgesics
Acetaminophen
Description:DistributedasTylenol.Givenpriortoandfollowingsurgeryfor48hours,ofteninconjunctionwith
otheranalgesics.Providesmildtomoderateanalgesia.Canbefoundinvarietyofsizetablets.Oftenitisconvenient
tousechildrensTylenolbecauseofthesmallernumberofmilligramspertablet.Tylenolcanbealsofoundinasyrup
form.
Usage:Formildanalgesia.
DosageandAdministration:10mg/kgP.O.2timesdaily.

OtherDrugs
Antibiotics
Antibioticsaresubstancesproducedbyvariousspeciesofmicroorganisms(bacteria,fungi,actinomycetes)that
suppressthegrowthofothermicroorganismsandeventuallymaydestroythem.However,commonusageoften
extendsthetermantibioticstoincludesyntheticantibacterialagents,suchasthesulfonamidesandquinolones,
whicharenotproductsofmicrobes.Hundredsofantibioticshavebeenidentified,andmanyhavebeendevelopedto
thestagewheretheyareofvalueinthetherapyofinfectiousdiseases.Antibioticsdiffermarkedlyinphysical,
chemical,andpharmacologicalproperties;antibacterialspectra;andmechanismsofaction.Weusethem:
1. Forsystemicinfectionsorillnesses
2. Forpreandpostsurgicalprofylaxis
3. Forthemaintenanceofimplants
Agentsofthefirstcategorywillonlybealwaysselectedforusebythedesignatedveterinarian.Nopersoninthe
laboratoryshouldeveradministerantibioticstothemonkeyswithoutpreviouslyconsultingtheveterinarian.
Specificagentsoftheothertwocategoriesareroutinelyusedforthemaintenanceofimplants,orbeforeand
afterthesurgery.Thefollowingdescribestheproperties,dosages,andtypesofadministrationoftheantimicrobial
drugsusedinthelab:
Ampicillin
Description:Ampicillinisasemisyntheticpenicillinderivedfromthebasicpenicillinnucleus,6aminopenicillanic
acid.AmpicillinisnotonlybactericidalagainstthegrampositiveorganismsusuallysusceptibletopenicillinG,but
alsoagainstthegramnegativebacteria.Itis,however,ineffectivefororganismswhichproducepenicillinase,
includingthepenicillinGresistantstrainsofstaphylococci.Weuseitforthetreatmentofskinandskinstructure
infectionscausedbybetalactamaseproducingstrainsofStaphylococcusaureus,E.coli,Klebsiellaspp.,andProteus
mirabilis;microbescommonlyfoundinmonkeyswithimplants.Itcanbealsogivenforinfectionscausedby
meningococcus,pneumococcus,gonococcus.
Usage:Localapplicationinchambersusedforsurfacecorticalrecordings.Ampicillinshouldbeusedifthe
susceptibilitytestshowssensitivityoftheculturedpathogenstothisdrug.
DosageandAdministration:Locallyca.0.5mlaftereachcleaningofthechamber.Systemically,thedosageis20
mg/kgevery8hours.Itisadministeredintramuscularly.
BacitracinOphthalmicOintment
Description:Bacitracinzinc(orpolymyxinBsulfate)ophthalmicointmentisasterileantimicrobialointmentfor
ophthalmicuse.Eachgramcontains:bacitracinzincequivalentto500bacitracinunits,polymyxinBsulfate
equivalentto10,000polymyxinBunits,andwhitepetrolatum.Bacitracinzincisthezincsaltofbacitracin,amixture
ofrelatedcyclicpolypeptides(mainlybacitracinA)producedbythegrowthofanorganismoftheLicheniformis
groupofBacillusSubtilisvarTracy.Ithasapotencyofnotlessthan40bacitracinunitspermg.PolymyxinBsulfateis
thesulfatesaltofpolymyxinB1andB2whichareproducedbythegrowthofBacillusPolymyxa(Prazmowski)Migula
(Fam.Bacillaceae).Ithasapotencyofnotlessthan6,000polymyxinBunitspermg,calculatedonananhydrous
basis.


Usage:AwiderangeofantibacterialactionisprovidedbytheoverlappingspectraofbacitracinandpolymyxinB
sulfate.Bacitracinisbactericidalforavarietyofgrampositiveandgramnegativeorganisms.Itinterfereswith
bacterialcellwallsynthesisbyinhibitionoftheregenerationofphospholipidreceptorsinvolvedinpeptidoglycan
synthesis.PolymyxinBisbactericidalforavarietyofgramnegativeorganisms.Itincreasesthepermeabilityofthe
bacterialcellmembranebyinteractingwiththephospholipidcomponentsofthemembrane.Bacitracinzincand
polymyxinBsulfatetogetherareconsideredactiveagainstthefollowingmicroorganisms:StaphylococcusAureus,
streptococciincludingStreptococcusPneumoniae,EscherichiaColi,HaemophilusInfluenzae,Klebsiella/Enterobacter
species,NeisseriaSpecies,andPseudomonasAeruginosa.Theproductdoesnotprovideadequatecoverageagainst
SerratiaMarcescens.Bacitracinisindicatedforthetopicaltreatmentofsuperficialinfectionsoftheexternaleyeand
itsadnexacausedbysusceptiblebacteria.Suchinfectionsencompassconjunctivitis,keratitisand
keratoconjunctivitis,blepharitisandblepharoconjunctivitis.
DosageandAdministration:Applytheointmentevery3or4hoursfor7to10days,dependingontheseverityof
theinfection.
Bacitracinneomycinpolymyxin
Description:Commonlyreferredtoastripleantibiotic,thisointmentisforexternaluseonly.Donotapplytothe
eye.
Usage:Weusethisaroundtheheadpostafterithasbeencleanedandpostoperativelyonthesurgicalwoundsto
preventinfections.
DosageandAdministration:Applyasneededdirectlyupontheinfectedarea.Usuallyonceaday.
Bactrim
Bactrim(trimethoprimandsulfamethoxazole)IVInfusion,isasterilesolutionforintravenousinfusiononly.Itisa
syntheticantibacterialcombinationproduct.Each5mLcontains80mgtrimethoprim(16mg/mL)and400mg
sulfamethoxazole(80mg/mL)compoundedwith40%propyleneglycol,10%ethylalcoholand0.3%diethanolamine;
1%benzylalcoholand0.1%sodiummetabisulfiteaddedaspreservatives,waterforinjection,andpHadjustedto
approximately10withsodiumhydroxide.
Excretionoftrimethoprimandsulfamethoxazoleisprimarilybythekidneysthroughbothglomerularfiltration
andtubularsecretion.Urineconcentrationsofbothtrimethoprimandsulfamethoxazoleareconsiderablyhigher
thanaretheconcentrationsintheblood.Thepercentofdoseexcretedinurineovera12hourperiodfollowingthe
intravenousadministrationofthefirstdoseof240mgoftrimethoprimand1200mgofsulfamethoxazoleonday1
rangedfrom17%to42.4%asfreetrimethoprim;7%to12.7%asfreesulfamethoxazole;and36.7%to56%astotal
(freeplustheN4acetylatedmetabolite)sulfamethoxazole.WhenadministeredtogetherasBactrim,neither
trimethoprimnorsulfamethoxazoleaffectstheurinaryexcretionpatternoftheother.Bothtrimethoprimand
sulfamethoxazoledistributetosputumandvaginalfluid;trimethoprimalsodistributestobronchialsecretions,and
bothpasstheplacentalbarrierandareexcretedinbreastmilk.Sulfamethoxazoleinhibitsbacterialsynthesisof
dihydrofolicacidbycompetingwithParaaminobenzoicacid(PABA).Trimethoprimblockstheproductionof
tetrahydrofolicacidfromdihydrofolicacidbybindingtoandreversiblyinhibitingtherequiredenzyme,dihydrofolate
reductase.Thus,Bactrimblockstwoconsecutivestepsinthebiosynthesisofnucleicacidsandproteinsessentialto
manybacteria.
Usage:BactrimIVInfusionisindicatedinthetreatmentofPneumocystisCariniipneumoniainhumansormonkeys,
andtreatmentofenteritiscausedbysusceptiblestrainsofShigellaFlexneriandShigellaSonnei.BactrimIVInfusionis
alsoindicatedinthetreatmentofsevereorcomplicatedurinarytractinfectionsduetosusceptiblestrainsof
EscherichiaColi,Klebsiellaspecies,Enterobacterspecies,MorganellaMorganiiandProteusspecies,whenoral

administrationofBactrimisnotfeasibleandwhenthe
organismisnotsusceptibletosingleagentantibacterials
effectiveintheurinarytract.WeuseBactrimbothlocallyinchambersandsystemically.
DosageandAdministration:15to20mg/kgperdayinthreeorfourequallydivideddosesevery6to8hoursforup
to14days.ForPneumoniathetotaldailydoseis15to20mg/kg(basedonthetrimethoprimcomponent)givenin3
or4equallydivideddosesevery6to8hoursforupto14days.Forsevereurinarytractinfectionsthetotaldailydose
is8to10mg/kg(basedonthetrimethoprimcomponent)givenin2or4equallydivideddosesevery6,8or12hours
forupto14daysforsevereurinarytractinfectionsand5daysforshigellosis.Themaximumrecommendeddaily
doseis60mLperday.
NotethatBactrimIVInfusionmustbediluted.Each5mlshouldbeaddedto125mlof5%dextroseinwater.
Afterdilutingwith5%dextroseinwaterthesolutionshouldnotberefrigeratedandshouldbeusedwithin6hours.If
adilutionof5mLper100mLof5%dextroseinwaterisdesired,itshouldbeusedwithin4hours.Ifuponvisual
inspectionthereiscloudinessorevidenceofcrystallizationaftermixing,thesolutionshouldbediscardedandafresh
solutionprepared.
Baytril
Description:Baytrilisthebrandnameforthesubstanceenrofloxacin.Enrofloxacinisasyntheticchemotherapeutic
agentfromtheclassofthequinolonecarboxylicacidderivatives.ItisaDNAgyraseinhibitor,wherebygyraseisa
synthesispromotingenzyme,essentialforbacteria.IthasantibacterialactivityagainstabroadspectrumofGram
negativeandGrampositivebacteria,includingPseudomonasaeruginosa,Klebsiellaspp.,Clostridiumperfringens,E.
coli,Enterobacterspp.,Staph.(coag.+),andStrep.(alphahemol.).
Usage:Enrofloxacinisoneofthemostimportantantibioticsforourlab,notonlybecauseithasabroadrangeof
activity,butalsobecauseitpenetratesalltissuesandbodyfluids,includingthebrain.Moreover,itisveryeffective
fortreatingdermalinfectionscausedbysusceptiblestrainsofEscherichiacoliandStaphylococcusaureus,the2most
commonbacteriaaroundtheimplants.Weuseitsystemicallyifananimalshasinfectedtissuesarounditsimplants.
DosageandAdministration:Enrofloxacinisoneoftheveryfewdrugswehavethatcanbeadministeredonceaday,
therebyeliminatingtheneedofinjectingtheanimalmultipletimesdaily.Itshouldbeusedwhenevermildto
moderateinfectionsarenoticed,anddefinitelybeforeandaftereverysurgicaloperation.Thedosageis5mg/kg/day
or1.5mg/kg2wiseaday.Ifpossible(iftheanimalisanesthetized)thedosagecanbedividedintwoinjectionsdaily.
Injectionshouldbegivenintramuscularly(IM).
Cephalothin
Description:Cephalothinisabroadspectrumantibioticactingagainststreptococci,staphylococci,Klebsiella,
salmonella.Itshouldbereservedforseriousinfections.
Usage:Drs.NeilLipmanandRobertMarini,theveterinariansatMIT,suggestedthisdrugstronglyformeningitis.It
shouldbeusedwithcaution,asitisasdangerousasthechloramphenicol.ItisdistributedasKeflinbyEliLillyandas
SeffinbyGlaxo.Inointmentitcanbealsousedfortheeye,ifacornealulcerispresent.Inthelattercasedonotuse
asteroidbasedophthalmicsolutionorointment.Ifindoubt,getveterinariantoexamineeye.Donotconfuse
Cephalothinwiththeregulartripleantibiotics(thatcannotbeappliedontheeye).
DosageandAdministration:Theointmentcanbeappliedtotheeye34timesdaily.Dosage2035mg/kgIV,IM,SQ,
twoorthreetimesperday.WeusuallyuseKeflin(100mg/ml).Forthisconcentrationthedosageduringsurgeryis
0.30ml/kgBacitracinneomycinpolymyxinhydrocortisone
Chloramphenicol
Description:Chloramphenicolisaverypotentantibioticthatshouldbereservedforseriousinfectionscausedby
susceptibleorganisms.Itentersthecerebrospinalfluidevenintheabsenceofmeningealinflammation,appearingin

concentrationsabouthalfofthosefoundintheblood.
Seriousandfatalblooddyscrasiasareknowntooccur
aftertheadministrationofchloramphenicol.Itmustnotbeusedwhenlesspotentiallydangerousagentswillbe
effective.Thissubstanceshouldbeadministeredwithgloveson.ItisdistributedasChloromycetinbyParkeDavis.
Usage:Weuseitmainlywhenmeningitisissuspected.
DosageandAdministration:50mg/kgperdayindivideddosesIVonly.
Cleocin
Description:CleocinphosphateSterileSolutioninvialscontainsClindamycinphosphate,awatersolubleesterof
Clindamycinandphosphoricacid.EachmLcontainstheequivalentof150mgClindamycin,0.5mgdisodiumedetate
and9.45mgbenzylalcoholaddedaspreservativeineachmL.
Usage:Clindamycinisanantibioticusedinthetreatmentofinfectionscausedbysusceptibleanaerobicbacteriaas
wellasforinfectionscausedbystreptococci,staphylococciandpneumococci.Anaerobicbacteriaareresponsiblefor
certainseriousrespiratorytractinfections,seriousskinandsofttissueinfections,septicemia.Clindamycinis
particularlyindicatedwhenpenicillinisinappropriate.SinceClindamycindoesnotdiffuseadequatelyintothe
cerebrospinalfluid,thedrugshouldnotbeusedinthetreatmentofmeningitis.ItshouldbenotedthatClindamycin
therapyhasbeenassociatedwithseverecolitiswhichmayendupbeingfatal.ItisdistributedasClindamycinby
Upjohn.
DosageandAdministration:20to40mg/kg/day(IMorIV)in3or4equaldoses.Thehigherdoseswouldbeusedfor
moresevereinfections.Asanalternativetodosingonabodyweightbasis,monkeysmaybedosedonthebasisof
squaremetersbodysurface:350mg/M(squared)/dayforseriousinfectionsand450mg/M(squared)/dayformore
severeinfections.Parenteraltherapymaybechangedtooralcleocin.Treatmentshouldbecontinuedforatleast10
days.
Erythromycin
Description:Erythromycinismainlyanorallyeffectiveantibiotic,andtheIVinjectionisindicatedonlywhenoral
administrationisimpossible.Itdoesnotpenetratethebloodbrainbarrier,butitdiffusesreadilyintointracellular
fluids,andantibacterialactivitycanbeachievedatessentiallyalltheothersites.Itcanbeusedforminor
streptococcalandstaphylococcalinfections
Usage:Usedinthechambersorsystemically,accordingtotheveterinariansinstructions.
DosageandAdministration:Erythromycinlactobionate1020mg/kgI.V.perday.Itmustbeadministeredby
continuousinfusion.Erythromycinethylsuccinatesuspensionsmaybeadministeredwithoutregardtomealsina
dosage1020mg/kg/dayinequallydivideddoses.Forsevereinfectionsthisdosagemaybedoubled.
GenopticOintmentandSolution(GentamycinOphthalmic)
Description:Genopticisasterile,topicalantiinfectiveagentforophthalmicuse.Gentamicinsulfateisawater
solubleantibioticoftheaminoglycosidegroup.GentamicinisobtainedfromculturesofMicromonosporaPurpurea.
ItisamixtureofthesulfatesaltsofgentamicinC1,C2,andC1A.Allthreecomponentsappeartohavesimilar
antimicrobialactivities.Gentamicinsulfateoccursasawhitetobuffpowderandissolubleinwaterandinsolublein
alcohol.EachmLcontainsgentamicinsulfateequivalentto3mg(0.3%)gentamicinbasewith:Liquifilm(r)(polyvinyl
alcohol)14mg(1.4%);benzalkoniumchloride,edetatedisodium,sodiumphosphate,dibasic;sodiumchloride;
hydrochloricacidand/orsodiumhydroxidetoadjustthepH;andpurifiedwater.Thesolutionisanaqueous,
bufferedsolutionwithapHof7.27.5.EachgramofGenopticointmentcontainsgentamicinsulfate,USP
(equivalentto3.0mggentamicin)inabaseofwhitepetrolatum,withmethylparaben(0.5mg)andpropylparaben
(0.1mg)aspreservatives.

Usage:InVitrogentamicinsulfateisactiveagainstmany strainsofthefollowingmicroorganisms:Staphylococcus
Aureus,StaphylococcusEpidermidis,StreptococcusPyogenes,StreptococcusPneumoniae,EnterobacterAerogenes,
EscherichiaColi,HaemophilusInfluenzae,KlebsiellaPneumoniae,NeisseriaGonorrhoeae,PseudomonasAeruginosa,
andSerratiaMarcescens.Genopticointmentandsolutionareindicatedinthetopicaltreatmentofocularbacterial
infectionsincludingconjunctivitis,keratitis,keratoconjunctivitis,cornealulcers,blepharitis,blepharoconjunctivitis,
acutemeibomianitis,anddacryocystitis,causedbysusceptiblestrainsofthefollowingmicroorganisms:
StaphylococcusAureus,StaphylococcusEpidermidis,StreptococcusPyogenes,StreptococcusPneumoniae,
EnterobacterAerogenes,EscherichiaColi,HaemophilusInfluenzae,KlebsiellaPneumoniae,NeisseriaGonorrhoeae,
PseudomonasAeruginosa,AndSerratiaMarcescens.
DosageandAdministration:Genopticsolution:Instilloneortwodropsintotheaffectedeye(s)everyfourhours.In
severeinfections,dosagemaybeincreasedtoasmuchastwodropseveryhour.Genopticointment:Applyasmall
amount(about1/2inch)totheaffectedeyetwotothreetimesaday.
NeosporinOphthalmicOintment
Description:NeosporinOphthalmicOintment(neomycinandpolymyxinBsulfatesandbacitracinzincophthalmic
ointment)isasterileantimicrobialointmentforophthalmicuse.Eachgramcontains:neomycinsulfateequivalentto
3.5mgneomycinbase,polymyxinBsulfateequivalentto10,000polymyxinBunits,bacitracinzincequivalentto400
bacitracinunits,andspecialwhitepetrolatum,q.s.NeomycinsulfateisthesulfatesaltofneomycinBandC,which
areproducedbythegrowthofStreptomycesFradiaeWaksman(Fam.Streptomycetaceae).Ithasapotency
equivalentofnotlessthan600mcgmofneomycinstandardpermg,calculatedonananhydrousbasis.PolymyxinB
sulfateisthesulfatesaltofpolymyxinB1andB2whichareproducedbythegrowthofBacillusPolymyxa
(Prazmowski)Migula(Fam.Bacillaceae).Ithasapotencyofnotlessthan6,000polymyxinBunitspermg,calculated
onananhydrousbasis.Bacitracinzincisthezincsaltofbacitracin,amixtureofrelatedcyclicpolypeptides(mainly
bacitracinA)producedbythegrowthofanorganismoftheLicheniformisgroupofBacillusSubtilisvarTracy.Ithasa
potencyofnotlessthan40bacitracinunitspermg.
Usage:Awiderangeofantibacterialactionisprovidedbytheoverlappingspectraofneomycin,polymyxinBsulfate,
andbacitracin.Neomycinisbactericidalformanygrampositiveandgramnegativeorganisms.Itisan
aminoglycosideantibioticwhichinhibitsproteinsynthesisbybindingwithribosomalRNAandcausingmisreadingof
thebacterialgeneticcode.PolymyxinBisbactericidalforavarietyofgramnegativeorganisms.Itincreasesthe
permeabilityofthebacterialcellmembranebyinteractingwiththephospholipidcomponentsofthemembrane.
Bacitracinisbactericidalforavarietyofgrampositiveandgramnegativeorganisms.Itinterfereswithbacterialcell
wallsynthesisbyinhibitionoftheregenerationofphospholipidreceptorsinvolvedinpeptidoglycansynthesis.
Neomycinsulfate,polymyxinBsulfate,andbacitracinzinctogetherareconsideredactiveagainstthefollowing
microorganisms:StaphylococcusAureus,streptococciincludingStreptococcusPneumoniae,EscherichiaColi,
HaemophilusInfluenzae,Klebsiella/Enterobacterspecies,Neisseriaspecies,andPseudomonasAeruginosa.The
productdoesnotprovideadequatecoverageagainstSerratiaMarcescens.
NeosporinOphthalmicOintmentisindicatedforthetopicaltreatmentofsuperficialinfectionsoftheexternaleye
anditsadnexacausedbysusceptiblebacteria.Suchinfectionsencompassconjunctivitis,keratitisand
keratoconjunctivitis,blepharitisandblepharoconjunctivitis.
DosageandAdministration:Applytheointmentevery3or4hoursfor7to10days,dependingontheseverityof
theinfection.
Panalog
Dosage:Panalogcreamcombinesnystatin,neomycinsulfate,thiostrepton,andtriamcinoloneacetonide(potent
corticosteroid).

Usage:Itprovidesfourbasictherapeuticeffects:anti
inflammatory,antipruritic,antifungalandantibacterial.
Donotuseifpusispresentsincethedrugmayallowtheinfectiontospread.
DosageandAdministration:Formildinflammations,applicationmayrangefromoncedailytoonceaweek.For
severeconditionsPanalogCreammaybeappliedasoftenas2to3timesdaily,ifnecessary.
Polytrim(trimethoprim&polymyxin)
Description:PolytrimOphthalmicSolution(trimethoprimsulfateandpolymyxinBsulfate)isasterileantimicrobial
solutionfortopicalophthalmicuse.EachmLcontainstrimethoprimsulfateequivalentto1mgtrimethoprimand
polymyxinBsulfate10,000units.Trimethoprimisasyntheticantibacterialdrugactiveagainstawidevarietyof
aerobicgrampositiveandgramnegativeophthalmicpathogens.Trimethoprimblockstheproductionof
tetrahydrofolicacidfromdihydrofolicacidbybindingtoandreversiblyinhibitingtheenzymedihydrofolate
reductase.Thisbindingisverymuchstrongerforthebacterialenzymethanforthecorrespondingmammalian
enzyme.Forthatreason,trimethoprimselectivelyinterfereswithbacterialbiosynthesisofnucleicacidsand
proteins.Whenusedtopically,trimethoprimandpolymyxinBabsorptionthroughintactskinandmucous
membranesisinsignificant.VitrostudieshavedemonstratedthattheantiinfectivecomponentsofPolytrimare
activeagainstthefollowingbacterialpathogensthatarecapableofcausingexternalinfectionsoftheeye:
StaphylococcusAureusandStaphylococcusEpidermidis,StreptococcusPyogenes,StreptococcusFaecalis,
StreptococcusPneumoniae,HaemophilusInfluenzae,HaemophilusAegyptius,EscherichiaColi,Klebsiella
Pneumoniae,ProteusMirabilis(indolenegative),ProteusVulgaris(indolepositive),EnterobacterAerogenes,and
SerratiaMarcescens.polymyxinB:PseudomonasAeruginosa,EscherichiaColi,KlebsiellaPneumoniae,Enterobacter
AerogenesandHaemophilusInfluenzae.
Usage:PolytrimOphthalmicSolutionisindicatedinthetreatmentofsurfaceocularbacterialinfections,including
acutebacterialconjunctivitis,andblepharoconjunctivitis,causedbysusceptiblestrainsofthefollowing
microorganisms:StaphylococcusAureus,StaphylococcusEpidermidis,StreptococcusPneumoniae,Streptococcus
Viridans,HaemophilusInfluenzaeandPseudomonasAeruginosa.
DosageandAdministration:ClinicalstudieshaveshownPolytrimtobesafeandeffectiveforuseinchildrenover
twomonthsofage.Thedosageregimenisthesameasforadults.
Tribrissen
Description:Tribrissenisacombinationof40mgtrimethoprimand200mgsulfadiazinein30mlof24%aqueous
suspensionforsubcutaneousadministration.Itisactiveagainstawidespectrumofbacterialpathogens,bothgram
negativeandgrampositive.Tribrissentherapyisindicatedinanimalswherepotentsystemicantibacterialaction
againstsensitiveorganismsisrequired.TribrissenisdistributedbyBurroughsWellcome.Tribrissenistheantibiotic
mostfrequentlyusedbeforeandaftersurgeryinthislaboratory.
Usage:Itisindicatedduringtreatmentofwoundinfectionsandabscesses,acuterespiratoryinfections,acute
septicemiaduetostreptococcuszooepidemicusetc.
DosageandAdministration:0.1mlof24%solutionperkgperday.Forsevereinfections,theinitialdosemaybe
followedbyonehalfthenormaldailydoseevery12hours.AdministerIMorsubcutaneously15mg/kg2timesa
day(totalof30mg/kg).

AdrenergicDrugs
Epinephrine
Description:Epinephrineisasympathomimeticdrug.Itisthemostpotentalphareceptoractivator.Itisgivenasan
emergencydoseforfailingcirculationorextremelycongestedrespiration.Itisnotusedincardiacfailureorin
hemorrhagic,traumatic,orcariogenicshock.Itisalsousedashemostaticagent.

Usage:Epinephrineisusedincardiacasystoleorincases whereapressoreffectisneededimmediatelytocounter
decreasesinbloodpressure.Phenylephrinecanalsobeusedtoelevatebloodpressure.Itisdistributedas
AdrenalineinjectionbyParkeDavisandasEpinephrineinjectionbyAstra,ElkinsSinnandAstra.Wegenerallyuseit
withsalineirrigationfluid,sinceitconstrictsbloodvesselsandthereforedecreasesbleeding.
DosageandAdministration:0.01mg/kgIVorIMforirrigation:1ml/200mlsaline.

Antiarrhythmics
Brevibloc
Description:Brevibloc(esmololHCL)isanantiarrhythmicdrugthatcanbeusedwhenevershorttermcontrolof
ventricularratewithashortactingagentisdesirable.Breviblocisrelativelyselectivebetablocker(beta1blocker).
Notethatifyougiveanonselectivebetablockerlikepropranolol,youwillcausebothadropinHRbutalsoadropin
bloodpressure,whichissometimesdangerousforthemonkey.Monkeyshaveonaverage145/85bloodpressure.
Bloodpressureabove150/95isconsideredtobehypertension.Breviblocisindicatedfortherapidcontrolof
ventricularrateinanimalswithatrialfibrillationoratrialflutter.Forexample,Breviblocisindicatedforthe
treatmentoftachycardiaandhypertension(itwilldosomethingsagainsthighpressureaswell.Selectivebutnot
specific)thatoccurduringinductionandtrachealintubation,duringsurgery,onemergencefromanesthesia,andin
thepostoperativeperiod.Yet,usageofthedrugforpreventingsucheventsisnotrecommended.
Warnings:Inclinicaltrials2050%ofhumanpatientstreatedwithBreviblochaveexperiencedhypotension,
generallydefinedassystolicpressurelessthan90mmHg(inmonkeysthisisabout80mmHg)and/ordiastolic
pressurelessthan50mmHg.Hypotensioncanoccuratanydosebutisdoserelatedsothatdosesbeyond0.2
mg/kg/minarenotrecommended.AllanimalstreatedwithBreviblocmustbecloselymonitored.Donotleaveyour
monkeyintherecoveryroomaloneordonotgetinvolvedinactivitiesthatareguaranteedtointerferewithyour
attendingtheanimal.Iftheanimalisanesthetizedandthedrugisbeinginfused,terminationoftheinfusionreverses
theeffectsofBreviblocwithin30minutes.Keepinmindthatcontinueddepressionofthemyocardiumwithbeta
blockingagentsoveraperiodoftimecan,insomecases,leadtocardiacfailure.Stoptheadministrationofthedrug
immediatelyifyounoticeanabnormalityintheanimalsECG.
Usage:Usethisdrugwithgreatcautioninthefollowingcases:(a)Tachycardiaduringtrachealintubation.(b)
Tachycardiaduringsurgery.Firstcheck,whetheranesthesiaisappropriate.Iftachycardiapersistdespiteappropriate
anesthesia,anddespitetheabsenceofanypainfulsurgicalmanipulation,thenadministerBrevibloc(0.5mg/kg/min
loadingdose),slowly.(c)Hypertensionduringsurgery.(d)Postsurgicalarrhythmias
DosageandAdministration:BrevibloccanbepurchasedasAmpuloramultidosevial.ThevialhasdilutedBrevibloc
(0.2mg/ml)andcanbeusedasis.The2.5gAmpul,however,isnotfordirectintravenousinjection.Thisdosageform
isaconcentrated,potentdrugwhichmustbedilutedpriortoitsinfusion.Breviblocshouldnotbeadmixedwith
sodiumbicarbonate.Breviblocshouldnotbemixedwithotherdrugspriortodilutioninasuitableintravenousfluid.
Todilute,asepticallypreparea10mg/mLinfusion,byaddingone2.5gAmpultoa250mLcontainer,ofacompatible
intravenoussolution.Breviblocinjectionwasfoundtobecompatiblewiththefollowingsolutionsandwasstablefor
atleast24hoursatcontrolledroomtemperatureorunderrefrigeration:
1. Dextrose(5%)Injection,USP
2. Dextrose(5%)inLactatedRinger'sInjection
3. Dextrose(5%)inRinger'sInjection
4. Dextrose(5%)andSodiumChloride(0.45%)Injection,USP
5. Dextrose(5%)andSodiumChloride(0.9%)Injection,USP

6. LactatedRinger'sInjection,USP
7. PotassiumChloride(40mEq/liter)inDextrose(5%)Injection,USP
8. SodiumChloride(0.45%)Injection,USP
9. SodiumChloride(0.9%)Injection,USP
10. BreviblocinjectionisnotcompatiblewithSodiumBicarbonate(5%)Injection,USP.

Antiemetics
Inapsine(Droperidol)
Description:Inapsine(droperidol)isaneuroleptic(tranquilizer)agentavailableinampoulesandvials.Eachmilliliter
contains2.5mgofdroperidolinanaqueoussolutionadjustedtopH3.4+/0.4withlacticacid.Inapsinein10mL
multidosevialsalsocontains1.8mgofmethylparabenand0.2mgpropylparaben.Droperidolischemicallyidentified
as1(1(3(pfluorobenzoyl)propyl)1,2,3,6tetrahydro4pyridyl)2benzimidazolinonewithamolecularweightof
379.43.Forchemicalstructure(s),clickhere,orusethebuttononthetoolbar.Inapsineisasterile,nonpyrogenic
aqueoussolutionforintravenousorintramuscularinjection.
Inapsine(droperidol)producesmarkedtranquilizationandsedation.Itallaysapprehensionandprovidesastate
ofmentaldetachmentandindifferencewhilemaintainingastateofreflexalertness.Inapsineproducesan
antiemeticeffectasevidencedbytheantagonismofapomorphineindogs.Itlowerstheincidenceofnauseaand
vomitingduringsurgicalproceduresandprovidesantiemeticprotectioninthepostoperativeperiod.Inapsine
potentiatesotherCNSdepressants.Itproducesmildalphaadrenergicblockade,peripheralvasculardilatationand
reductionofthepressoreffectofepinephrine.Itcanproducehypotensionanddecreasedperipheralvascular
resistanceandmaydecreasepulmonaryarterialpressure(particularlyifitisabnormallyhigh).Itmayreducethe
incidenceofepinephrineinducedarrhythmias,butitdoesnotpreventothercardiacarrhythmias.Theonsetof
actionofsingleintramuscularandintravenousdosesisfromthreetotenminutesfollowingadministration,although
thepeakeffectmaynotbeapparentforuptothirtyminutes.Thedurationofthetranquilizingandsedativeeffects
generallyistwotofourhours,althoughalterationofalertnessmaypersistforaslongastwelvehours.
Usage:Inapsine(droperidol)isindicated:toproducetranquilizationandtoreducetheincidenceofnauseaand
vomitinginsurgicalanddiagnosticprocedures.Forpremedication,induction,andasanadjunctinthemaintenance
ofgeneralandregionalanesthesia.inneuroleptanalgesiainwhichInapsineisgivenconcurrentlywithanopioid
analgesic,suchasSublimaze(fentanylcitrate)Injection,toaidinproducingtranquilityanddecreasinganxietyand
pain.
DosageandAdministration:Dosageshouldbeindividualized.Someofthefactorstobeconsideredindetermining
thedoseareage,bodyweight,physicalstatus,underlyingpathologicalcondition,useofotherdrugs,typeof
anesthesiatobeusedandthesurgicalprocedureinvolved.Vitalsignsshouldbemonitoredroutinely.Formonkeysa
doseaslowas1.0to1.5mg(0.4to0.6mL)per20to25poundsisrecommendedforpremedicationorforinduction
ofanesthesia.
Promethazine
Preventionandcontrolofvomiting,asanadjuncttoanalgesicsforthecontrolofpostoperativepain.Itis
contraindicatedfollowingadministrationoflargedosesofbarbituratesornarcotics.ItisdistributedasPhenerganby
Wyeth.Dosage25mgIMsingledoseevery6hours.

RespiratoryStimulants
DopramV
Description:DopramisabrandnameofDoxapramHydrochloride.Doxapramis1ethyl4(2morpholinoethyl)3,3
diphenyl2pyrrolidinonehydrochloridehydrate.Doxapramstimulatesprimarilyrespirationbyaneffectonthebrain
stem,sincesectioningofreflexpathwaysdonotabolishitsaction.Thedetectionofincreasedelectricalactivityin
boththeinspiratoryandexpiratorycentersofthemedulla,atdosesaslowas0.2mg/kgconstitutesconfirmationof
thistypeofaction.Onlyafterhighdoseswereotherpartsofthebrainandspinalcordstimulated.Doxapramdoes
notproduceconvulsionsasreadilyasotherstimulants.Excessivedoesmayproducetohyperventilationwhichmay
leadtorespiratoryalkalosis.
Therespiratorystimulanteffectsofdoxapramarenotblocked(atleastindogs)byanestheticdosesofthe
following:phenobarbitalsodium,pentobarbitalsodium,thiopentalsodium,halothane,methoxyflurane.Itstimulates
respirationthatwasdepressedseverelybymorphineormeperidine.Theactionofdoxapramisrapidusually
beginninginafewseconds.Thedurationandintensityofresponsedependsuponthedoes,theconditionsofthe
animalatthetimethedrugisadministered,anddepthofanesthesia.Dopramisavailablein20mLmultipledose
vialsofthesterilesolution.Theconcentrationis20mg/mL.
Usage:Incasesofrespiratoryarrestduetooverdosewithbarbiturates.
DosageandAdministration:Thedosageofdoxaprammustbeadjustedfordepthofanesthesia,respiratoryvolume
andrate.Dosagecanberepeatedin15to20minutes,ifnecessary.Dopramisadministeredintravenously(IV)only.
Dosageforbarbiturateanesthesiais2.55mg/kg.Dosageforgasanesthesiais0.5mg/kg.

AntiinflammatoryAgents
Decadron(Dexamethasone)
Description:Decadron(Dexamethasonesodiumphosphate),asyntheticadrenocorticalsteroid,isawhiteorslightly
yellow,crystallinepowder.Itisfreelysolubleinwaterandisexceedinglyhygroscopic.Eachmilliliterofdecadron
Phosphateinjection,4mg/mL,containsdexamethasonesodiumphosphateequivalentto4mgdexamethasone
phosphateor3.33mgdexamethasone.InactiveingredientspermL:8mgcreatinine,10mgsodiumcitrate,sodium
hydroxidetoadjustpH,andWaterforInjectionq.s.,with1mgsodiumbisulfite,1.5mgmethylparaben,and0.2mg
propylparabenaddedaspreservatives.EachmilliliterofdecadronPhosphateinjection,24mg/mL,contains
dexamethasonesodiumphosphateequivalentto24mgdexamethasonephosphateor20mgdexamethasone.
InactiveingredientspermL:8mgcreatinine,10mgsodiumcitrate,0.5mgdisodiumedetate,sodiumhydroxideto
adjustpH,andWaterforInjectionq.s.,with1mgsodiumbisulfite,1.5mgmethylparaben,and0.2mg
propylparabenaddedaspreservatives.
DecadronPhosphateinjectionhasarapidonsetbutshortdurationofactionwhencomparedwithlesssoluble
preparations.Becauseofthis,itissuitableforthetreatmentofacutedisordersresponsivetoadrenocorticalsteroid
therapy.Naturallyoccurringglucocorticoids(hydrocortisoneandcortisone),whichalsohavesaltretaining
properties,areusedasreplacementtherapyinadrenocorticaldeficiencystates.Theirsyntheticanalogs,including
dexamethasone,areprimarilyusedfortheirpotentantiinflammatoryeffectsindisordersofmanyorgansystems.
Glucocorticoidscauseprofoundandvariedmetaboliceffects.Inaddition,theymodifythebody'simmuneresponses
todiversestimuli.Atequipotentantiinflammatorydoses,dexamethasonealmostcompletelylacksthesodium
retainingpropertyofhydrocortisoneandcloselyrelatedderivativesofhydrocortisone.
Usage:Preoperatively,andintheeventofserioustraumaorillness,inpatientswithknownadrenalinsufficiencyor
whenadrenocorticalreserveisdoubtfulShockunresponsivetoconventionaltherapyifadrenocorticalinsufficiency
existsorissuspected.

DosageandAdministration:DecadronPhosphate
injection,4mg/mLForIntravenous,Intramuscular,
Intraarticular,Intralesional,AndSoftTissueInjection.DecadronPhosphateinjection,24mg/mLForIntravenous
InjectionOnly.DecadronPhosphateinjectioncanbegivendirectlyfromthevial,oritcanbeaddedtoSodium
ChlorideInjectionorDextroseInjectionandadministeredbyintravenousdrip.Solutionsusedforintravenous
administrationorfurtherdilutionofthisproductshouldbepreservativefreewhenusedintheneonate,especially
theprematureinfant.Whenitismixedwithaninfusionsolution,sterileprecautionsshouldbeobserved.Since
infusionsolutionsgenerallydonotcontainpreservatives,mixturesshouldbeusedwithin24hours.
Neodecadron
Description:TheOphthalmicOintmentNeodecadroncontainsineachgram:dexamethasonesodiumphosphate
equivalentto0.5mg(0.05%)dexamethasonephosphateandneomycinsulfateequivalentto3.5mgneomycinbase.
Inactiveingredients:whitepetrolatumandmineraloil.Corticosteroidssuppresstheinflammatoryresponsetoa
varietyofagents,andtheyprobablydelayorslowhealing.Sincecorticosteroidsmayinhibitthebody'sdefense
mechanismagainstinfection,aconcomitantantimicrobialdrugmaybeusedwhenthisinhibitionisconsideredtobe
clinicallysignificantinaparticularcase.
Whenadecisiontoadministerbothacorticosteroidandanantimicrobialismade,theadministrationofsuch
drugsincombinationhastheadvantageofgreaterpatientcomplianceandconvenience,withtheaddedassurance
thattheappropriatedosageofbothdrugsisadministered,plusassuredcompatibilityofingredientswhenbothtypes
ofdrugareinthesameformulationand,particularly,thatthecorrectvolumeofdrugisdeliveredandretained.The
relativepotencyofcorticosteroidsdependsonthemolecularstructure,concentration,andreleasefromthevehicle.
TheantiinfectivecomponentinOphthalmicOintmentNeodecadronisincludedtoprovideactionagainstspecific
organismssusceptibletoit.NeomycinsulfateisactiveInVitroagainstsusceptiblestrainsofthefollowing
microorganisms:StaphylococcusAureus,EscherichiaColi,HaemophilusInfluenzae,Klebsiella/Enterobacterspecies,
andNeisseriaspecies.Theproductdoesnotprovideadequatecoverageagainst:PseudomonasAeruginosa,Serratia
Marcescens,andstreptococci,includingStreptococcusPneumoniae.
Usage:Forsteroidresponsiveinflammatoryocularconditionsforwhichacorticosteroidisindicatedandwhere
bacterialinfectionorariskofbacterialocularinfectionexists.Ocularsteroidsareindicatedininflammatory
conditionsofthepalpebralandbulbarconjunctiva,cornea,andanteriorsegmentoftheglobewheretheinherent
riskofsteroiduseincertaininfectiveconjunctivitisisacceptedtoobtainadiminutioninedemaandinflammation.
Theyarealsoindicatedinchronicanterioruveitisandcornealinjuryfromchemical,radiation,orthermalburns,or
penetrationofforeignbodies.Theuseofacombinationdrugwithanantiinfectivecomponentisindicatedwhere
theriskofinfectionishighorwherethereisanexpectationthatpotentiallydangerousnumbersofbacteriawillbe
presentintheeye.Theparticularantiinfectivedruginthisproductisactiveagainstthefollowingcommonbacterial
eyepathogens:

StaphylococcusAureus

EscherichiaColi

HaemophilusInfluenzae

Klebsiella/Enterobacterspecies

Neisseriaspecies

Theproductdoesnotprovideadequatecoverageagainst:

PseudomonasAeruginosa

SerratiaMarcescens

Streptococci,includingStreptococcusPneumoniae

DosageandAdministration:Thedurationoftreatmentwillvarywiththetypeoflesionandmayextendfromafew
daystoseveralweeks,accordingtotherapeuticresponse.ApplyathincoatingofOphthalmicOintment
Neodecadronthreeorfourtimesaday.Whenafavorableresponseisobserved,reducethenumberofdaily
applicationstotwo,andlatertooneadayasmaintenancedoseifthisissufficienttocontrolsymptoms.
SoluMedrol(Methylprednisolone)
Description:SoluMedrolSterilePowdercontainsmethylprednisolonesodiumsuccinateastheactiveingredient.
Methylprednisolonesodiumsuccinate,USP,occursasawhite,ornearlywhite,odorlesshygroscopic,amorphous
solid.Itisverysolubleinwaterandinalcohol;itisinsolubleinchloroformandisveryslightlysolubleinacetone.
Naturallyoccurringglucocorticoids(hydrocortisoneandcortisone),whichalsohavesaltretainingproperties,are
usedasreplacementtherapyinadrenocorticaldeficiencystates.Theirsyntheticanalogsareprimarilyusedfortheir
potentantiinflammatoryeffectsindisordersofmanyorgansystems.Glucocorticoidscauseprofoundandvaried
metaboliceffects.Inaddition,theymodifythebody'simmuneresponsestodiversestimuli.Methylprednisoloneisa
potentantiinflammatorysteroidsynthesizedintheResearchLaboratoriesofTheUpjohnCompany.Ithasagreater
antiinflammatorypotencythanprednisoloneandevenlesstendencythanprednisolonetoinducesodiumand
waterretention.Methylprednisolonesodiumsuccinatehasthesamemetabolicandantiinflammatoryactionsas
methylprednisolone.Whengivenparenterallyandinequimolarquantities,thetwocompoundsareequivalentin
biologicactivity.TherelativepotencyofSoluMedrolSterilePowderandhydrocortisonesodiumsuccinate,as
indicatedbydepressionofeosinophilcount,followingintravenousadministration,isatleastfourtoone.Thisisin
goodagreementwiththerelativeoralpotencyofmethylprednisoloneandhydrocortisone.
Usage:Incasesofbraininjuryduetoelectrodesortoimplantedguidetubes.Notethatconvulsionshavebeen
reportedwithconcurrentuseofmethylprednisoloneandcyclosporin.Drugsthatinducehepaticenzymessuchas
phenobarbital,phenytoinandrifampinmayincreasetheclearanceofmethylprednisoloneandmayrequireincreases
inmethylprednisolonedosetoachievethedesiredresponse.Drugssuchastroleandomycinandketoconazolemay
inhibitthemetabolismofmethylprednisoloneandthusdecreaseitsclearance.Therefore,thedoseof
methylprednisoloneshouldbetitratedtoavoidsteroidtoxicity.Methylprednisolonemayincreasetheclearanceof
chronichighdoseaspirin.Thiscouldleadtodecreasedsalicylateserumlevelsorincreasetheriskofsalicylate
toxicitywhenmethylprednisoloneiswithdrawn.Aspirinshouldbeusedcautiouslyinconjunctionwith
corticosteroidsinpatientssufferingfromhypoprothrombinemia.Theeffectofmethylprednisoloneonoral
anticoagulantsisvariable.Therearereportsofenhancedaswellasdiminishedeffectsofanticoagulantwhengiven
concurrentlywithcorticosteroids.Therefore,coagulationindicesshouldbemonitoredtomaintainthedesired
anticoagulanteffect.
DosageandAdministration:Whenhighdosetherapyisdesired,therecommendeddoseofSoluMedrolSterile
Powderis30mg/kgadministeredintravenouslyoveratleast30minutes.Thisdosemayberepeatedevery4to6
hoursfor48hours.Ingeneral,highdosecorticosteroidtherapyshouldbecontinuedonlyuntilthepatient's
conditionhasstabilized;usuallynotbeyond48to72hours.Althoughadverseeffectsassociatedwithhighdose
shorttermcorticoidtherapyareuncommon,pepticulcerationmayoccur.Prophylacticantacidtherapymaybe
indicated.Inotherindicationsinitialdosagewillvaryfrom10to40mgofmethylprednisolonedependingonthe
clinicalproblembeingtreated.Thelargerdosesmayberequiredforshorttermmanagementofsevere,acute

conditions.Theinitialdoseusuallyshouldbegivenintravenouslyoveraperiodofseveralminutes.Subsequentdoses
maybegivenintravenouslyorintramuscularlyatintervalsdictatedbythepatient'sresponseandclinicalcondition.
Corticoidtherapyisanadjunctto,andnotreplacementforconventionaltherapy.Dosagemaybereducedforinfants
andchildrenbutshouldbegovernedmorebytheseverityoftheconditionandresponseofthepatientthanbyage

orsize.Itshouldnotbelessthan0.5mgperkgevery24
710days.

hours.Forstrokesweuse0.5mg/kg2timesadayIMfor

Dosagemustbedecreasedordiscontinuedgraduallywhenthedrughasbeenadministeredformorethanafew
days.Ifaperiodofspontaneousremissionoccursinachroniccondition,treatmentshouldbediscontinued.Routine
laboratorystudies,suchasurinalysis,twohourpostprandialbloodsugar,determinationofbloodpressureandbody
weight,andachestXrayshouldbemadeatregularintervalsduringprolongedtherapy.UpperGIXraysare
desirableinpatientswithanulcerhistoryorsignificantdyspepsia.SoluMedrolmaybeadministeredbyintravenous
orintramuscularinjectionorbyintravenousinfusion,thepreferredmethodforinitialemergencyusebeing
intravenousinjection.Toadministerbyintravenous(orintramuscular)injection,preparesolutionasdirected.
AnticoagulantsandAnticoagulantAntidotes

Anticoagulants
Heparin
Description:HeparinSodiumInjection,USPisasterilesolutionofheparinsodiumderivedfrombovinelungtissue,
standardizedforanticoagulantactivity.Heparinisaheterogeneousgroupofstraightchainanionic
mucopolysaccharidescalledglycosaminoglycanshavinganticoagulantproperties,thatispreventingbloodclotting.
Fulldoseheparintherapyusuallyisadministeredbycontinuousintravenousinfusion.TheUSPunitofheparinisthe
quantitythatprevents1.0mlofcitratedsheepplasmafromclottingfor1houraftertheadditionof0.2mlof1%
CaCl2.Treatmentisinitiatedwithabolusinjectionof5000U,followedby1200to1600Uperhourdeliveredbyan
infusionpump.TherapyroutinelyismonitoredbytheaPTT.Aclottingtimeof1.5to2.5timesthenormalmeanaPTT
value(usually50to80seconds)istherapeutic.Theriskofrecurrenceofthromboembolismisgreaterinpatientswho
donotachievethislevelofanticoagulationwithinthefirst24hours.Initially,theaPTTshouldbemeasuredandthe
infusionrateadjustedevery6hours;doseadjustmentsmaybeaidedbyuseofanomogram.Onceasteadydosage
scheduleisestablished,dailymonitoringissufficient.
Subcutaneousadministrationofheparincanbeusedforthelongtermmanagementofpatientsinwhomwarfarinis
contraindicated(e.g.,duringpregnancy).Atotaldailydoseofabout35,000Uadministeredasdivideddosesevery8
to12hoursusuallyissufficienttoachieveanaPTTof1.5timesthecontrolvalue(measuredmidwaybetweendoses).
Monitoringgenerallyisunnecessaryonceasteadydosagescheduleisestablished.
Lowdoseheparintherapysometimesisusedprophylacticallytopreventdeepvenousthrombosisand
thromboembolisminsusceptiblepatients,e.g.,postoperatively.Asuggestedregimenforsuchtreatmentis5000U
ofheparingivensubcutaneouslyevery8to12hours.Laboratorymonitoringisunnecessary,sincethisregimendoes
notprolongtheaPTT.

Usage:WeuseitinsterilesalinetoflushIVcatheters.Wealsouseitintherinsesolutionforaperfusion.
DosageandAdministration:Dosageis2units/mlsalineWeusuallyusethe1,000units/mlconcentration.Forthis
concentrationthedosageis0.5ml/(250mlsaline[0.9%sodiumchloride]).HeparinistobeadministeredIVorby
deepsubcutaneousroutes.
Protamine
Description:Protaminesaresimpleproteinsoflowmolecularweight,richinarginineandstronglybasic.This
stronglybasicnatureaccountsfortheirantiheparineffectwhichmakesitausefulantidotetoheparinoverdose.Itis
distributedassuchbyEliLilly.
Usage:IncasesofHeparinOverdose(Shouldneverhappen!)

DosageandAdministration:ItshouldbegivenIVvery
Eachmgprotamineneutralizes90USPunitsofheparin.

slowly;notmorethan50mginevery10minuteperiod.

Diuretics
Furosemide
Description:Furosemideisapotentdiureticwhichiseffective510minutesafterIVadministration.
Usage:Weuseitforthecontrolofintracranialpressure.ItisdistributedasLasixbyHoechstRoussel.
DosageandAdministration:28mg/kgIV.

AntidiarrhealCompounds
Lomotil
Description:Lomotil(Searle&Co)isanantidiarrhealcompound.Itisacombinationofdiphenoxylate(2.5mg)and
atropine(0.25mg)Theetiologyoftheproblemshouldbedeterminedbeforeusingthisdrug.
Usage:Incasesofseverediarrhea.
DosageandAdministration:2mg(adults),1mg(infants)1/2tablet.

ReplacementFluids
LactatedRingersSolution
Description:Polyionic,isotonicsolutionforfluidtherapy.Forthemonkeythewaterlossintermsofbodyweightis
(1)Respiratory/cutaneouslosses15ml/kg,(2)Fecal10ml/kg,and(3)Urinary20ml/kgperday,withtotallossof
approx.4050ml/kg/dayor2ml/kg/hr.Theexactdriprateshouldbeadjustedforeachprocedure.Awater
deprivedanimalshouldbegivenreplacementfluidsalongwithmaintenancefluids.
Usage:Inallsurgeriesformaintainingthemonkeysfluidrequirementsduringtheoperativeperiod.Duringsurgery
waterisalsolostfromthesurgicalsite,fromthevasculareffectsofanestheticagents,andfromsequestrationof
interstitialfluidsfromsurgicaltrauma.Totallossisapprox.2.5ml/kg/hr.FormaintenanceuseisotonicLactated
Ringers(0.18%)with4%Dextrose,orplainLactatedRingers(0.9%).OurIVdrips(pediatric)give60drops/ml
(Drp/ml).Dropsperminute(dpm)arecomputedbasedon:dpm=(Drp/ml)*(ml/kg/hr)*Weight/60
DosageandAdministration:315ml/kg/hr.

SummaryofDrugsforMacaques

DrugDosageChartsforMPIK
Drugs

Dosage

0.020.05mg/kgIM
0.0050.01mg/kgIM

Duration

Anticholinergics

Atropine
Glycopyrrolate
Dissociatives

Ketamine

520mg/kgIM
Ketamine&xylazine7mg/kg&0.6mg/kgIM
Ketamine&xylazine10mg/kg&0.252mg/kgIM
Tiletamine&zolazepam
1.53.0mg/kgIM

1530min

1530min

45138min
&46mg/kgIM4560min

Barbiturate Anesthetics

Pentobarbital
Pentobarbital
Thiopental

2030mg/kgIV(induction)

8mg/kgif15mg/kgKetamineused
57mg/kgIV(induction)

3060min

2.55mg/kgIV(induction)
0.30.4mg/kg/min(infusion)

510min

Non-barbiturate Anesthetics

Propofol
Propofol

Neuroleptanalgesics

Fentanyldroperidol(InnovarVet)
Fentanylfluanisone(Hypnorm)

0.10.3ml/kgIM

0.3ml/kgIM

Opioid Analgesics

Fentanyl

Sufenta

Sufentamite
Morphine
Oxymorphone
Meperidine
Buprenophrine

0.003mg/kgIV

0.01mg/kg
0.01mg/kg

12mg/kgIM

0.15mg/kgIM
2mg/kgIM

0.01mg/kgIM

15min

46hr

4hr
68hr

Non-Opioid Analgesics

Aspirin

Aspiringrectalsuppositories
Ketorolac

325mgPO
125mg/5kg

1530mgIM

Drugs

Dosage

Duration

Muscle Relaxants

Pancuronium
Vecuronium
Atracurium

0.080.1mg/kgIVfollowedby03ug/kg/min
0.040.06mg/kgIVfollowedby0.4ug/kg/min
0.250.3mg/kgIVfollowedby1.5ug/kg/min

4hr

Anticholinesterases

Neostigmine

0.05mg/kg

Inhalation Anesthetics

NitrousOxide

Halothane
Isoflurane
Enflurane
Desflurane
Desflurane

Additionof30%reducesMAC
Halothanefrom1.15to0.75%
Enfluranefrom1.84to1.46%
1MAC=0.891.15%
1MAC=1.28%
1MAC=1.84%
1MAC=6.4%ifnoFentanylisused
1MAC=3.5%ifFentanylisused

5mg
0.05mg/kg
5mg/kg
0.04mg/kg

Miscellaneous

Valium
Brevibloc
Dopram
Naloxon