пеницилин

Introductiontothecompound

Basicinformation

Chinesename:penicillin

Chinesealias:penicillin

Englishname:benzylpenicillin

Englishalias:cilloral;pradupen;Ursopen;benzylpenicillin;cosmopen;

CASNumber:61-33-6

Molecularformula:C₁₆H₁₈N₂O₄S

Molecularweight:334.39000

Accuratemass:334.09900

PSA:112.01000

LogP:1.18960

Physicalandchemicalproperties

Density:1.42g/cm³

Boilingpoint:663.3ºCat760mmHg

Flashpoint:355ºC

Refractiveindex:1.655

Storageconditions:ventilated,lowtemperatureanddry

Safetyinformation

Customscode:32041900

WGKGermany:2

Hazardcategorycode:R42/43

Safetyinstructions:S36/37

RTECSnumber:XH9700000

Dangerousgoodsmark:Xn

R&DHistory

Beforethe1940s,humanshadnotbeenabletomasteradrugthatcouldeffectivelytreatbacterialinfectionswithlowsideeffects.Ifsomeonehastuberculosisatthattime,itmeansthatthepersonwilldiesoon.Inordertochangethissituation,scientificresearchershavecarriedoutlong-termexploration,butthebreakthroughprogressmadeinthisregardisduetoanaccidentaldiscovery.

Inmoderntimes,in1928,BritishbacteriologistFlemingfirstdiscoveredtheworld'sfirstantibiotic,penicillin.AlexanderFlemingdiscoveredpenicillinduetoaluckymistake.

In1928,BritishscientistFlemingfirstdiscoveredpenicillininexperimentalresearch,butduetothelackofadvancedtechnologyanddeepunderstandingatthattime,Flemingdidnotseparatepenicillinalone.

In1929,Flemingpublishedhisresearchresults.Unfortunately,thispaperhasnotreceivedtheattentionofthescientificcommunitysinceitwaspublished.

Whenviewingthepetridishwithamicroscope,Flemingfoundthatthestaphylococcalcoloniessurroundingthemoldhadbeendissolved.ThismeansthatacertainsecretionofmoldcaninhibitStaphylococcus.Thesubsequentidentificationshowedthattheabove-mentionedmoldwasPenicilliumspp.Therefore,Flemingcalledtheantibacterialsubstancesecretedbyitaspenicillin.Unfortunately,Fleminghasnotbeenabletofindawaytoextracthigh-puritypenicillin,sohecultivatedthepenicilliumstrainsforgenerations,andin1939providedthestrainstotheBritishpathologistFlo,whowaspreparingtosystematicallystudypenicillin.Li(HowardWalterFlorey)andbiochemistQianEn.

In1938,theGermanchemistErnstChannsawFleming’spaperinapileofoldbooks,andbegantodopurificationexperiments.

FloryandChanre-experimentedwithpenicillinin1940.TheyinjectedeightmicewithalethaldoseofStreptococcusandthentreatedfourofthemwithpenicillin.Withinafewhours,onlythefourmicethathadbeentreatedwithpenicillinwerealiveandhealthy.Sincethen,aseriesofclinicaltrialshaveconfirmedtheefficacyofpenicillinonvariousbacterialinfectionssuchasstreptococcusanddiphtheriabacillus.Thereasonwhypenicillincankillbacteriawithoutharminghumancellsisthatthepenicillanecontainedinpenicillincanhinderthesynthesisofthecellwallofthebacteria,causingthebacteriatodissolveanddie,whilehumanandanimalcellshavenocellwall.

Inthewinterof1940,QianEnextractedalittlepenicillin.Althoughthiswasamajorbreakthrough,itwasfarfromclinicalapplication.

In1941,thebatonofpurificationofpenicillinwaspassedtothehandsofAustralianpathologistWalterFlory.WiththeassistanceoftheU.S.military,Floryseparatedstrainsfromthesoilbroughtbackfromtheairportsofvariouscountrieswhenthepilotswentoutformissions,increasingtheproductionofpenicillinfrom2unitspercubiccentimeterto40units.

About1941,thepathologistHowardFloryofOxfordUniversityinEnglandandthebiochemistQianEnrealizedtheseparationandpurificationofpenicillin,anddiscovereditscurativeeffectoninfectiousdiseases,butpenicillincanmakesomepeopleAnallergicreactionoccurs,soaskintestmustbedonebeforeapplication.Mostoftheantibioticsusedareextractedfrommicrobialculturefluid,andsomeantibioticscanbesynthesizedartificially.Becausedifferenttypesofantibioticshavedifferentchemicalcomponents,theirmechanismofactiononmicroorganismsisalsoverydifferent.Someinhibitthesynthesisofproteins,someinhibitthesynthesisofnucleicacids,andsomeinhibitthesynthesisofcellwalls.

Throughaperiodofintenseexperimentation,FloryandChannfinallyusedfreeze-dryingtoextractpenicillincrystals.Later,Floryfoundamoldonamelonthatcouldextractalargeamountofpenicillin,andusedcornflourtoprepareacorrespondingculturesolution.Drivenbytheseresearchresults,Americanpharmaceuticalcompaniesbeganmassproductionofpenicillinin1942.

By1943,pharmaceuticalcompanieshaddiscoveredawaytomass-producepenicillin.AtthattimeBritainandtheUnitedStateswereatwarwithNaziGermany.Thisnewdrugisveryeffectiveincontrollingwoundinfections.

InOctober1943,FlorysignedthefirstbatchofpenicillinproductioncontractswiththeUSmilitary.PenicillinwasbornattheendofWorldWarIIandquicklyreversedthebattleoftheAllies.Afterthewar,penicillinwaswidelyused,savingtensofmillionsoflives.By1944,thesupplyofmedicinewassufficienttotreatallAlliedsoldierswhoparticipatedinthewarduringtheSecondWorldWar.Becauseofthisgreatinvention,in1945,Fleming,FloryandChannwontheNobelPrizeinPhysiologyorMedicineforthe"discoveryofpenicillinanditsclinicaleffects".

In1945,BritishchemistD.C.HodgkinusedX-raydiffractiontodeterminethemolecularstructureofpenicillin.

OnSeptember5,1944,China'sfirstbatchofdomesticallyproducedpenicillinswasborn,unveilingthehistoryofChina'sproductionofantibiotics.Asoftheendof2001,China'sannualoutputofpenicillinaccountedfor60%oftheworld'stotalannualoutputofpenicillin,rankingfirstintheworld.

In2002,Biroletal.proposedamodelbasedontheprocessmechanism.Theprocesscomprehensivelyconsideredthevariousphysiologicalchangesofmicroorganismsduringfermentationandfoundthatthisisaverycomplicatedprocess.Inordertostudythepenicillinprocessmoreconveniently,Birolextendedthenon-structuralmodelproposedbyBajpaiandReuss,andfurthersimplifiedthemodeltofacilitateresearch.

Mainfunctions

Penicillinisanimportantantibioticwithhighefficiency,lowtoxicityandwideclinicalapplication.Itssuccessfuldevelopmentgreatlyenhancedtheabilityofhumanstoresistbacterialinfectionsandledtothebirthoftheantibioticfamily.Itsappearanceopenedupanewerainthetreatmentofdiseaseswithantibiotics.Throughdecadesofimprovement,penicillininjectionandoralpenicillinhavebeenabletotreatpneumonia,meningitis,endocarditis,diphtheria,anthraxandotherdiseasesrespectively.Followingpenicillin,antibioticssuchasstreptomycin,chloramphenicol,oxytetracycline,tetracycline,etc.continuetobeproduced,enhancingtheabilityofhumanstotreatinfectiousdiseases.Butatthesametime,theresistanceofsomebacteriaisgraduallyincreasing.Inordertosolvethisproblem,researchersarecurrentlydevelopingmorepotentantibiotics,exploringhowtopreventgermsfromacquiringresistancegenes,anddevelopingantibacterialdrugsusingplantsasrawmaterials.

Penicillincannottoleratetheenzymesproducedbydrug-resistantstrains(suchasdrug-resistantStaphylococcusaureus),andiseasilydestroyedbyit,anditsantibacterialspectrumisnarrow,anditismainlyeffectiveagainstGram-positivebacteria.PenicillinGcanbedividedintopotassiumsaltandsodiumsalt.Potassiumsaltcannotbedirectlyinjectedintravenously.Whenintravenousinfusion,theamountofpotassiumionsmustbecarefullycalculatedtoavoidtheformationofhyperkalemiaandinhibitheartfunctionandcausedeath.

Thetoxicityofpenicillinantibioticsisverysmall.Becauseβ-lactamsactonthecellwallofbacteria,whilehumanshaveonlycellmembraneswithoutcellwalls,theyarelesstoxictohumans.Inadditiontocausingsevereallergicreactions,Undernormaldosage,itstoxicityisnotobvious.

Tousethisproduct,anintradermaltestmustbedonefirst.Penicillinallergytestincludesskintestmethod(referredtoaspenicillinskintest)andinvitrotestmethod,ofwhichintradermalinjectionismoreaccurate.Theskintestitselfisalsodangerous.About25%ofpatientswhodiefromanaphylacticshockdiefromtheskintest.Therefore,adequaterescuepreparationsshouldbemadeduringskintestorinjectionadministration.Whenchangingtoadifferentbatchofpenicillin,itisalsonecessarytorepeattheskintest.Thedrypowdercanbestoredformanyyearswithoutexpiration,buttheinjectionsolutionandtheskintestsolutionareunstable,anditisbettertoprepareitfresh.Andforthosewithrenaldysfunction,thedosageshouldbeadjustedappropriately.Inaddition,topicalapplicationhasmanychancesofsensitization,andbacteriaarepronetodrugresistance,soitisnotrecommended.

Classification

Picillinwasusedclinicallyintheearly1940s.Afteralotofresearchonpenicillin,somepenicillinwasdiscovered.Whenpeoplechemicallymodifiedpenicillin,someeffectivepenicillinwasobtained.Semi-syntheticpenicillins.Inthe1970s,somepenicillinswerefoundfrommicrobialmetabolitesthataresimilartopenicillinandalsocontainβ-lactamringsinsteadoftetrahydrothiazoleringstructures.Thesepenicillinscanbedividedintothreegenerations:Thefirst-generationpenicillinreferstonaturalpenicillin,suchaspenicillinG(benzylpenicillin);thesecond-generationpenicillinreferstothesemi-syntheticpenicillinbychangingthesidechainofpenicillinnucleus-6-aminopenicillanicacid(6-APA),Suchasmethicillin,carbenicillin,andampicillin;thethird-generationpenicillinhasacorestructurewiththesameβ-lactamringaspenicillin,butdoesnothaveatetrahydrothiazolering,suchasthiomycinandnocardinWhite.

Accordingtoitscharacteristics,itcanbedividedinto:

PenicillinG:suchaspenicillinGpotassium,penicillinGsodium,long-actingCillin`penicillinG,peillinG,penicillin,penicillin,penicillinsodium,benzylpenicillinsodium,penicillinpotassium,benzylpenicillinpotassium,etc.

PenicillinV:(alias:phenoxymethylpenicillin,6-phenoxyacetamidopenicillanoicacid)suchaspenicillinVpotassium(includingavarietyofdosageforms)).

Enzyme-resistantpenicillin:suchasoxacillin(XinqingII),chlorazolepenicillin,etc.

Ampicillin:suchasampicillin,amoxicillin,etc.

Anti-pseudomonaspenicillin:suchascarbenicillin,piperacillin,ticarcillin,etc.

MecillinanditsestersofPimethicillin:SuchasmecillinanditsestersofPimethicillin,etc.,whicharemoreresistanttoenzymesandareresistanttocertainnegativebacilli(suchaslargeintestine,gramLebsiellaandSalmonella)areeffectivebutpoorlyeffectiveagainstPseudomonasaeruginosa.

Methicillins:suchastamoxicillin,etc.

Preparationmethod

Theproductionmethodofnaturalpenicillinandsemi-syntheticpenicilliniscompletelydifferent.

[Naturalpenicillin]

TheproductionofpenicillinGcanbedividedintotwosteps:strainfermentationandextractionandpurification.①Fermentationofstrains:inoculatethePenicilliumchrysogenumonasolidmediumandcultivatefor7-10daysat25°CtoobtainasporecultureofPenicillium.Usesterilewatertomakeasuspensionofsporesandinoculateitintothesterilizedmediumintheseedtank,passinsterileair,stir,andincubateat27°Cfor24to28hours,andtheninoculatetheseedculturesolutionintothefermentor.Inthesterilizedmediumcontainingthephenylaceticacidprecursor,sterileairwaspassedthrough,stirred,andculturedat27°Cfor7days.Thephenylaceticacidprecursorandanappropriateamountofculturemediumneedtobesupplementedduringthefermentationprocess.②Extractionandpurification:coolingandfilteringthepenicillinfermentationbroth.Thefiltrateissubjectedtomulti-stagecountercurrentextractionwithbutylacetateintheextractionmachineundertheconditionofpH2to2.5toobtainthebutylesterextract,whichistransferredtothebuffersolutionofpH7.0to7.2,andthentransferredtothebutylester.Thisbutylesterextractisdecolorizedbyactivatedcarbon,addedwithasalt-formingagent,andsubjectedtoazeotropicdistillationtoobtainpenicillinGpotassiumsalt.PenicillinGsodiumsaltispreparedbypassingpenicillinGpotassiumsaltthroughionexchangeresin(sodiumtype).

[Semi-syntheticpenicillin]

Using6APAasanintermediateandavarietyofchemicallysynthesizedorganicacidsforacylationreaction,varioustypesofSemi-syntheticpenicillin.

6APAisobtainedbycleavingpenicillinGorVwithpenicillinacylaseproducedbymicroorganisms.Enzymereactionisgenerallycarriedoutundertheconditionsof40～50℃andpH8～10;enzymeimmobilizationtechnologyhasbeenappliedtotheproductionof6APA,whichsimplifiesthecleavageprocess.6APAcanalsobemadebychemicallycrackingfrompenicillinG,butthecostishigher.Theintroductionofthesidechainistofirstmakethecorrespondingorganicacidintoanacidchloridewithachlorinatingagent,andthenuseaninorganicororganicbaseasacondensingagenttocarryoutanacylationreactionwith6APAaccordingtothestabilityoftheacidchlorideinwaterororganicsolvents.Thecondensationreactioncanalsobecarriedoutdirectlyinthelysatewithoutseparating6APA.

[Penicillinconcentrationmethod]

Amethodofusingpenicillintospecificallykillwild-typecellsandretainauxotrophiccells.Penicillincaninhibitthesynthesisofbacterialcellwalls,soitcanonlykillbacteriathataregrowingandreproducing,butnotbacteriathatstopdividing.Intheselectiveliquidmediumthatcanonlygrowthewildtypebutnotthemutanttype,thewildtypeiskilledbypenicillin,whilethemutanttypeisnotkilled,sothatthewildtypeiseliminatedandthemutanttypeisconcentrated.Itcanbeappliedtobacteriaandactinomycetes,andisoneofthecommonmethodsforscreeningauxotrophicmutants.

Drugdescription

Pharmacologicalefficacy

Picillinantibioticsarethegeneraltermforalargeclassofantibioticsinβ-lactams,duetotheactionofβ-lactamsBecauseofthecellwallsofbacteria,humanshaveonlycellmembraneswithoutcellwalls.Penicillinantibioticshavelittletoxicityandaretheantibioticswiththehighestchemotherapyindex.However,thecommonallergicreactiontopenicillinantibioticsranksfirstamongvariousdrugs,withanincidenceofupto5%to10%.Itisaskinreaction,showingrash,angioedema,andthemostseverecaseisanaphylacticshock,mostlyafterinjectionItoccurswithinafewminutes,andthesymptomsaredyspnea,cyanosis,bloodpressuredrop,coma,stifflimbs,andfinallyconvulsions.Failuretorespondintimecancausedeath.

Variousroutesofadministrationorapplicationofvariouspreparationscancauseanaphylacticshock,butinjectionshavethehighestincidence.Theoccurrenceofallergicreactionshasnothingtodowiththesizeofthedrugdose.Peoplewhoarehighlyallergictothisproductcancauseshockeveninverysmallamounts.Injectionintothebodycancauseepilepticseizures.Large-doselong-terminjectionistoxictothecentralnervoussystem(suchascausingconvulsions,coma,etc.),anditcanberecoveredbystoppingthedrugorreducingthedose.

Oraluseiseasilydestroyedbygastricacidanddigestiveenzymes.Afterintramuscularinjectionorsubcutaneousinjection,theabsorptionisfaster,andthepeakbloodconcentrationisreachedwithin15-30minutes.Penicillinhasashorthalf-lifeinthebodyandismainlyexcretedintheurineinitsoriginalform.

Thepharmacologicaleffectofpenicillinistointerferewiththesynthesisofbacterialcellwalls.ThestructureofpenicillinissimilartotheD-alanyl-D-alanineinthestructureofthecellwallmucopeptide.Itcancompetewiththelatterfortranspeptidase,hindertheformationofmucopeptides,causecellwalldefects,andmakebacterialosetheircellwalls.Permeablebarrier,killingbacteria.

Pharmacokinetics

Picillinisnotacidresistantandshouldnotbetakenorally.Afterintramuscularinjection,thepeakbloodconcentration(Cmax)isreachedwithin0.5hours,whichcanbewidelydistributedintissuesandbodyfluids,andeasilypenetratesintoinflammatorytissues.Theconcentrationinthechest,abdominalcavityandjointcavityfluidisabout50%oftheserumconcentration.Thisproductcanpassthroughtheplacenta,butitisdifficulttopassthroughtheblood.Thecerebrospinalfluidbarrier,milkmaycontainasmallamountofpenicillin,whichisnoteasytopenetrateintotheeyes,bonetissues,areaswithoutbloodsupplyandabscesses.Theplasmaproteinbindingrateis45%-65%,andthebloodeliminationhalf-life(t1/2β)isabout30minutes.Itcanbeextendedto2.5-10hoursforpeoplewithimpairedrenalfunction,anditcanalsobeextendedfortheelderlyandnewborns.About19%ofthisproductismetabolizedintheliver,mainlysecretedandexcretedthroughtherenaltubules.Undernormalrenalfunction,about75%ofthedoseisexcretedfromthekidneywithin6hours,andasmallamountisexcretedthroughthebiliarytract.Hemodialysiscanremovethisproduct,butperitonealdialysiscannot.

Combinedreaction

Theproblemofdrugabuseintheclinichascausedsomeadversereactions,especiallythecompatibilityofpenicillinwithotherdrugs.Theinteractionsandadversereactionsproducedcannotbeignoredof.

1.Penicillincannotbecombinedwithsimilarantibiotics

Becausetheirantibacterialspectrumandantibacterialmechanismaremostlysimilar,thecombinedeffectisnotadditive.Onthecontrary,combinedmedicationaggravateskidneydamage,andcanalsocausedyspneaorrespiratoryarrest.Thereiscross-resistancebetweenthem,andthecombinedapplicationoftwoβ-lactamantibioticsisnotrecommended.

2.Penicillincannotbeusedincombinationwithsulfadrugsandtetracyclines

Picillinisa"bactericide"duringthebreedingperiod,whichhindersthesynthesisofbacterialcellwallsTetracyclineisa"bacteriostaticagent",whichaffectsthesynthesisofbacterialprotein.Thecombinedeffectofthetwoisanantagonisticeffect.Undernormalcircumstances,itshouldnotbeusedincombination.Clinicaldatashowthattheantibacterialefficacyofpenicillinaloneis90%,theefficacyofsulfadrugsaloneis81%,andtheantibacterialefficacyofthecombinationofthetwodrugsis75%.Itcannotbeusedincombinationunlesstherearespecialcircumstances.

3.Penicillincannotbemixedwithaminoglycosidedrugsforinfusion

Mixingthetwoisthesameastheinfusionsetforpatientinfusion,becauseoftheβ-lactamofpenicillinGentamicincanbeinactivated.Themechanismisachemicalinteractionbetweenthetwo.Therefore,mixedapplicationisstrictlyprohibited.Penicillinintravenousdripandgentamicinintramuscularinjectionshouldbeused.

Tosumup,theimpropercombinationofpenicillin,duetodruginteractions,leadingtoadversedrugreactionscannotbeunderestimated.Penicillinisthemostcommonlyusedantibioticforthetreatmentofvariousinfectiousdiseases.Strictlygrasptheindicationsofthemedication,rationallyuseitincombination,andtakeeffectivemeasurestoreduceunnecessaryadversereactions.

⒋Chloramphenicol,erythromycin,tetracyclines,sulfadrugsandotherbacteriostaticagentscaninterferewiththebactericidalactivityofpenicillin,andshouldnotbecombinedwithpenicillins,especiallyinthetreatmentofmeningitisorseverecasesthatrequirerapidsterilizationWheninfected.

⒌Probenecid,aspirin,indomethacin,phenylbutazone,andsulfadrugscanreducetheexcretionofpenicillinsintherenaltubules,therebyincreasingthebloodconcentrationofpenicillinsandmaintainingthemforalongtime.Thehalf-lifeisprolonged,andtoxicitymayalsoincrease.

⒍Picillinpotassiumorsodiumisincompatiblewithheavymetals,especiallycopper,zincandmercury,becausethelattercandestroytheoxidizedthiazoleringofpenicillin.Rubbertubesorbottlestoppersmadeofzinccompoundscanalsoaffecttheviabilityofpenicillin.Acidicglucoseinjectionortetracyclineinjectioncandestroytheactivityofpenicillin.Penicillincanalsobeinactivatedbyoxidizingorreducingagentsorhydroxylcompounds.

⒎Ceflotin,lincomycin,tetracycline,vancomycin,erythromycinethylsuccinate,amphotericinB,norepinephrine,meta-hydroxylamine,phenytoinsodium,hydroxyhydrochlorideareaddedtopenicillinintravenousinfusionTurbiditywillappearafteroxazine,prochlorperazine,promethazine,vitaminBgroup,vitaminC,etc.Therefore,theproductshouldnotbeinstilledtogetherwithotherdrugs.

⒏Penicillincanenhancetheeffectofwarfarin.

⒐Aftertheproductismixedwithaminoglycosideantibiotics,theantibacterialactivityofthetwodrugsissignificantlyweakened,sothetwodrugscannotbeadministeredinthesamecontainer.

Drugtoxicity

Penicillinallergy

Itisquicklyabsorbedafteroraladministration,about75%～90%canbeabsorbedfromthegastrointestinaltract.Foodhasnosignificanteffectondrugabsorption.Itsproteinbindingrateis17%-20%,andthehalf-decayperiodofbloodelimination(t1/2)is1to1.3hours.Aftertakingthedrug,about24%to33%ofthedoseisIntrahepaticmetabolism,within6hours,46%to68%ofthedoseisexcretedintheurineastheprototypedrug,andsomedrugsareexcretedthroughthebiliarytract.Theserumhalf-lifeofpatientswithsevererenalinsufficiencycanbeextendedto7hours.Serumdialysiscanremovepenicillin,butperitonealdialysishasnoeffectonremovingtheproduct.

Picillinistheleasttoxicsideeffectofvariousantibiotics,becauseitsmechanismofactionistodestroytheprocessandstructureofcellwallformation,andthehumanbodyhasnocellwall.Penicillinhasbasicallynopharmacologicaltoxicitytothehumanbody,butlargedosesofpenicillinmayalsocausenervoussystempoisoning.Themainreasonforthesideeffectsofpenicillinistheinsufficientpurificationofpenicillin,andtheimpuritiesinitareeasytomakethehumanbodyallergic.

⒈Allergicreactions:Penicillinallergicreactionsaremorecommon,rankingfirstamongvariousdrugs.Severeallergicreactionsareanaphylacticshock(typeIallergy),theincidencerateis0.004%to0.015%,typeIIallergiesarehemolyticanemia,drugeruption,contactdermatitis,interstitialnephritis,asthmaattacks,etc.,typeIIIallergiesThereaction,theserotypereaction,isalsomorecommon,withanincidenceof1%to7%.Patientswithanaphylacticshockwhoarenotrescuedintimehaveahighmortalityrate.Therefore,onceitoccurs,itmustberescuedonthespot,immediatelygivethepatientanintramuscularinjectionof0.1%epinephrine0.5-1ml,ifnecessary,dilutewith5%glucoseorsodiumchlorideinjectionforintravenousinjection,iftheclinicalmanifestationdoesnotimprove,repeatithalfanhourlater.Iftheheartbeatstops,adrenalinecanbeinjectedintotheheart.Atthesametime,intravenousinfusionoflargedosesofadrenalcortexhormonestosupplementbloodvolume;patientswithpersistentlypersistentbloodpressurewillbegivenvasoactivedrugssuchasdopamine.Canalsoconsidertheuseofantihistaminestorelieveurticaria.Patientswithbreathingdifficultiesshouldbegivenoxygeninhalationorartificialrespiration,andthosewithobviouslaryngealedemashouldhaveatracheotomyintime.Theapplicationofpenicillinaseisoflittlesignificance.

Principleofallergy

Picillinisunstableandcanbedecomposedintopenicillinthiazolicacidandpenicillonicacid.Theformercanbepolymerizedintopenicillinthiazolicacidpolymer,combinedwithpolypeptidesorproteinstoformpenicilliumthiazolicacidprotein,whichisanimmediateallergenandthemaincauseofallergicreactions;thelattercanalsointeractwithcysteine​​inthebodyAcidformsadelayedallergen-penicillinacidprotein,whichisrelatedtoserumsickness-likereactions.

⒉Toxicreaction:Penicillintoxicreactionisrare,andperipheralneuritismayoccurintheareaof​​intramuscularinjection.Intrathecalinjectionofmorethan20,000unitsorintravenousinfusionoflargedosesofpenicillincancausemuscleclonus,convulsions,comaandotherreactions(penicillinencephalopathy),whicharemorecommonininfants,theelderlyandpatientswithimpairedrenalfunction.Penicillincanoccasionallycausepsychoticepisodes,andindividualpatientsmayexperienceanxiety,fever,shortnessofbreath,highbloodpressure,rapidheartrate,hallucinations,convulsions,coma,etc.aftertheapplicationofprocainepenicillin.Themechanismofthisreactionisunknown.

⒊Doubleinfection:Penicillin-resistantStaphylococcusaureus,Gram-negativebacilliorCandidaalbicansinfectioncanoccurduringtreatmentwithpenicillin.Over-proliferationofCandidacanmakethetonguecoatingbrownorevenblack.

⒋Hyperkalemia(hypokalemia)andhypernatremia:Ifalargeamountofpenicillinpotassiumisadministeredintravenously,hyperkalemiaorpotassiumpoisoningmayoccur.High-dosepenicillinsodium,especiallyforpatientswithimpairedrenalfunctionorcardiacinsufficiency,cancausehypernatremia.Aftergivingpatients100millionunitsofpenicillinsodiumdaily,asmallnumberofpatientsmaydevelophypokalemia,metabolicalkalosisandhypernatremia.

⒌Hertzianreactionandtreatmentcontradiction:whenpenicillinisusedtotreatsyphilis,leptospirosisorotherinfections,symptomsmayincrease.ItiscalledHerxianreaction,whichisasystemicreactioncausedbythekillingofalargenumberofpathogens.Treatmentcontradictionsarealsoseeninpatientswithsyphilis,becausethesyphilislesionsdisappeartooquicklyaftertreatment,butthetissuerepairisslow,orthefibroustissueshrinks,whichhindersorganfunction.

6.Veterinaryclinicalallergiesaregenerallymild,mainlymanifestedassweating,excitement,restlessness,muscletremor,dyspnea,rapidheartrate,unstablestanding,sometimeshives,eyelidandfacialedema,Vulvaandrectumswellingandasepticcellulitis,shockandevendeathinseverecases.

[Cause]

Penicillinisunstableandcanbedecomposedintopenicillinthiazolicacidandpenicillonicacid.Theformercanbepolymerizedintopenicillinthiazolicacidpolymer,combinedwithpolypeptidesorproteinstoformpenicilliumthiazolicacidprotein,whichisanimmediateallergenandthemaincauseofallergicreactions;thelattercanalsointeractwithcysteine​​inthebodyAcidformsadelayedallergen-penicillinacidprotein,whichisrelatedtoserumsickness-likereactions.Patientswithahistoryofdrugallergyorallergicreactionshaveahigherincidenceoftopicalmedicationsandlong-actingpreparations.

Inclinicaluse,hightemperature,acid-base,andheavymetalionsshouldbeavoided.TrytoavoidusingglucoseinjectionwithanacidicPHvalueasasolvent,andwhenusing0.9%sodiumchlorideasasolvent,itshouldbepreparedimmediately,otherwiseitwillbeplacedfortoolonganditwillcausethedecompositionofpenicillin.Causestheoccurrenceofallergicreactions.

[Firstaidmeasures]

⒈Stopthemedicationimmediately,liedown,andrescueonthespot,withheadlowandfeethigh.

⒉Subcutaneousinjectionof0.1%epinephrinehydrochloride0.5～1ml,childrencanreduceit,andthensubcutaneousinjectionof0.5mleveryhalfanhour,untiltheriskperiod,addcorticosteroidsorantihistaminesifnecessary.

⒊Patientswithcardiacarrestshouldundergocardiacchestcompressionorintracardiacinjectionof0.1%epinephrinehydrochloride1ml.

⒋Oxygeninhalation,mouth-to-mouthartificialrespirationwhenbreathingisinhibited,andintramuscularinjectionofnicotinicacidorlobelineandotherrespiratorystimulants.

Laryngealedemaaffectsthetracheotomyduringbreathing.

⒌Usehydrocortisone200mg,ordexamethasone5-10mginto50%Glucose40mlintravenousinjection,oradd5-10%Glucose500mlintravenously.

⒍Vasoactivedrugssuchasdopamine,alamin,etc.canbeusedaccordingtotheneedsofthedisease.

⒎Correctacidosisandtheapplicationofhistaminedrugs.

⒏Keepwarm,preventcolds,keepnursingrecords,anddonotmove.

⒐AcupunctureacupuncturepointsinRenzhong,Neiguan,Yintang,Hegu,Yongquan,etc.

⒑MoxamoxibustioncanbeusedatacupointssuchasNeiguan,Hegu,Yongquan,Guanyuan,andZhongwan.

Penicillinencephalopathy

Picillinencephalopathyisararecentralnervoussystemtoxicreactionofpenicillin.Usuallyonlyasmallamountofpenicillinpassesthroughtheblood-brainbarrier.Whentheintravenousinfusionspeedistoolarge,alargeamountofdrugswillquicklyenterthebraintissue,thatis,theconcentrationofthedruginthebloodandcerebrospinalfluidwillincrease,whichinterfereswithnormalnervefunctionsandcausesseverecentralnervoussystemresponses,suchashyperreflexia,impairedperception,andhallucinations,Convulsions,lethargy,etc.,called"penicillinencephalopathy."

Thepathogenesisofpenicillinencephalopathyisunknown.Thereasonisthatthedruginhibitsthesynthesisandtransportofcentralnervoussysteminhibitorytransmitterγ-aminobutyricacid(GABA)toacertainextent,andinhibitscentralnervoussystemNa+-K+-ATPasereducestherestingmembranepotential.Someliteraturebelievesthatitmayberelatedtothecationsinthesodiumsaltofpenicillin.Itisbelievedthatthetoxiceffectsofsodium,lithium,ammonium,strontium,calcium,magnesium,andpotassiumincreaseinorder.Inaddition,itisrelatedtothepurityofthepreparation,individualdifferences,dosesize,injectionmethod,speed,Theconcentrationisallrelated.SomescholarshaveprovedthatwhentheconcentrationofpenicillinGinthecerebrospinalfluidexceeds8u-10u/ml,toxicreactionscanoccur.Somepeoplethinkthatthepoorfunctionoftheblood-brainbarrieristhemainreason.Afterpenicillinentersthebody,90%isexcretedbythekidneys.Infantshavepoorkidneyfunction,whichprolongstheirhalf-life,increasestheirbloodconcentration,increasestoxicity,andproducesneurotoxiceffects.Leadtoincreasedexcitabilityofthebrain-convulsions,thatis,"penicillinencephalopathy.Atpresent,itisrecommendedthatthedosageofpenicillinininfantsis<600,000u/kg·d,andneonates<400,000u/kg·d.Patientswithinsufficiencyandpoorcirculationshouldbeusedwithcaution.

Duetothedeclineinrenalfunctionintheelderly,penicillinandotherbroad-spectrumpenicillinshaveaprolongedhalf-life?Forexample,penicillinGintravenouslyhasahalf-lifeof0.55ina25-year-oldyouthThehalf-lifeofprocainepenicillinis10hoursin25-year-oldsand18hoursin70-year-olds;thehalf-lifeofprocainepenicillinis1.0hoursin70-year-olds;dicloxacillinislessthan30-years-oldThehalf-lifeis0.88hours,anditis3.97hoursintheelderlyover65yearsold;thehalf-lifeofamoxicillinis1hourto1.5hoursintheyoungpeople,and2.67hoursinthe89-year-oldelderly.Atthesametime,duetotheplasmaalbuminoftheelderlyThereductioninproductionisonly3.7%forthoseover75yearsold.Therefore,theabsorbedantibioticsinthebloodshowacorrespondingreductioninthecombinedstate,andthefreepartthereofrisesinthebloodandtissues.WhentheelderlyuselargedosesofpenicillinGandcarbenicillin,Neurologicaltopsychiatricsymptomsmayoccur,suchashyperreflexia,perceptualdisturbances,hallucinations,convulsions,lethargy,etc.,aswellastemporarymentaldisorders,proneto"penicillinencephalopathy".

Duetotheblood-brainbarrierfunctioninchildrenAndrenalfunctionisimmature,largedosesofpenicillincansignificantlyincreasetheconcentrationofcerebrospinalfluid,whichhasatoxiceffectonthecentralnervoussystem,leadingtopenicillinencephalopathy.Inaddition,onemillionpenicillinGsodiumcontainsNa+39mg,andonemillionpenicillinGpotassiumcontainsK+66mg,whenalargeamountofintravenousinjectionshouldpayattentiontotheretentionofK+andNa+inthebody.Itisalsoeasytoform"penicillinencephalopathy".

Whenthesystemicdosageofpenicillins,especiallypenicillinG,istoolargeortheintravenousdripistoofast,Theconcentrationofpenicillininthecerebrospinalfluidexceeds8U/ml,whichcandirectlystimulatethecerebralcortex,causingseverereactionssuchasconvulsions,convulsions,epilepsyandevencoma.Itusuallyappearswithin24-72haftermedication.Itoftenoccursinnewborns,childrenandtheelderly.,Becausethedrugeasilypenetratestheblood-brainbarrier.Forpatientswithrenaldysfunctionorrenalfailure,itisalsopronetooccurduetodrugexcretiondisorders.

Peripheralneuritismayoccurinthepenicillinintramuscularinjectionarea。Intrathecalinjectionofmorethan20,000unitsorintravenousinfusionoflargedosesofpenicillincancausemuscleclonus,convulsions,comaandotherreactions.Thisreactionismorecommonininfants,theelderlyandpatientswithimpairedrenalfunction.Penicillincanoccasionallycausepsychoticepisodes.UseIndividualpatientsmayexperiencehighfever,anxiety,fever,etc.afterprocainepenicillin.

Theconditionisserious.Themainmanifestationisthesuddenappearanceofconvulsions,dehydration,hypoxia,shortnessofbreath,andbloodproductiononthebasisoftheoriginaldisease.Chemicalchanges(suchashypoglycemia,hyponatremia,acidemia),highbloodpressure,rapidheartrate,hallucinations,convulsions,coma,andrespiratoryfailure,etc.Themechanismofthisreactionisunknown.Somechildrenmayalsohavelimbparalysisandfontanelle.TheclosedchildcanseethefontanelleBeginning,asmallnumberofchildrenmayhaveuncoordinatedmovements.Theabovesymptomsmostlyappear1to2weeksaftertheoriginalillness.

Thecomalastsforalongtimeandmayhaveserioussequelae.Thesequelaemayincludedullness,blindness,deafness,paralysis,etc.Asmallnumberofpatientsmaydieduetoseriousillness.

[Treatment]

⒈StoppenicillinIfpenicillinencephalopathyoccurs,stoppenicillinintime.2.Takeoxygenimmediately.Forcomapatients,sputumshouldbesuckedout,breathingshouldbekeptunobstructed,andoxygenshouldbesuppliedintimeforalongerperiodoftimetopromotetheresolutionofcerebraledema.Ifnecessary,performtracheotomyandartificialrespiration.3.Anticonvulsant,usesedativeandantipsychoticdrugs,intramuscularinjectionofluminalsodium,diazepam,etc.4.Adrenalcortexhormones.Forexample,hydrocortisone,prednisone,anddexamethasoneallhavetheeffectofquicklyreducinginflammationandreducingedema,andshouldbeusedforshort-termuse,generallywithinaweek.5.Anti-cerebraledemadrug20%​​mannitolisinjectedintravenously.Itshouldbeusedrepeatedlyincasesofrepeatedintracranialpressureincreasetopreventbrainherniation.Atthesametime,fastdiureticscanbeaddedtoenhancetheeffectofdehydratingagents.6.Strengthendialysisandcooperatewithhemoperfusion,bloodpurification,etc.7.Properlyhandlehighfever,dehydration,bloodchemistrychanges(suchashypoglycemia,hyponatremia,acidemia),andrespiratoryfailure.8.Speed​​uptheeliminationofdrugsandreducementalsymptoms.9.Energysupporttherapy.Toxicitycanbemetabolizedwithinafewhoursortensofhours,butthepoisonednervesarestillinastateofparalyticshock.Ifthenervesinparalyticshockarenotactivatedandnourishedbyearlytreatment,theinvolvednerveswillbeprolongedduetoischemia.Delayedischemicpathologicalchanges,medicallycalleddelayedneurologicaldamage,itisdifficulttorecover.10.Theprognosisofmostpatientswiththisdiseaseisgood,andthesymptomsdisappearwithin24hoursafterpropertreatment,andthereisnosequelae.Ifthecomalastsforseveraldaystoseveralweeks,itmaycauseserioussequelaesuchasinsufficiency,blindness,deafness,rigidlimbs,inflexibility,orparalysisinchildren.Asmallnumbercandieinarelativelyshortperiodoftimeduetorespiratoryfailure.

[Precautions]

⒈Amongthesideeffectsofpenicillin,anaphylacticshockisfatal.Itoftenattractspeople’sattentionandmanifestsasencephalopathyandsurroundingTheneurotoxiceffectofnervedamageiseasilyoverlooked.Thepreviousbeliefthatpenicillinisrarelypoisonedaslongasitisnotallergicmustbedispelled.Donotabusepenicillin(includingotherantibiotics)inlargedoses.Whenyoumustuseit,useintravenousinfusionaslittleaspossible.Theelderlyandchildrenshoulduseitwithcaution;inaddition,Itshouldalsobenotedthatwhenpenicillinisusedincombinationwithampicillin,itismorelikelytocausepenicillinencephalopathy.

Whentheelderlyuseantibacterialdrugs,theeffectoftheeliminationprocessissignificantlyslower.

⒉Penicillinwasoriginallyahighlyeffectiveandlow-toxicantibiotic.Ithasmadegreatachievementsinthehistoryofhumananti-infection,anditsreputationhasnotdiminished.Probablybecauseofthis,thereisatrendthatpenicillinisusedmoreandmorewidely,andthedoseisincreasingdaybyday.Asmallnumberofmedicalstaffgivepatientsalargeamountofpenicillinintravenously,especiallytheintravenousinfusionofmorethan8millionunits,andsomeofthemhaveusedthedrugseveraltimesadayandcontinuouslyforseveraldays.Thisnotonlycausestheconcentrationofpenicillininthebloodtoremainhigh,butalsomakestheconcentrationofpenicillininthecerebrospinalfluidgraduallyincrease.Whentheconcentrationinthecerebrospinalfluidis>8units/ml,itwillstimulatethebrainnervesandthenappearhyperreflexia,sensorydisturbances,hallucinations,Convulsions,comaandotherencephalopathysymptomscanalsocausetransientmentaldisorders,especiallythosewithrenalinsufficiency,theelderlyandchildrenaremorelikelytoinducethisdisease.

⒊Duetothedeclineofrenalfunctionandthedecreaseofplasmaalbumin,bloodconcentrationandcerebrospinalfluiddrugconcentrationincrease,resultingincentralnervoussystemtoxicity.Therefore,whenantibioticsareusedintheelderly,thedosageshouldbeadjustedaccordingtorenalfunction.Inordertopreventtheoccurrenceof"penicillinencephalopathy",thedosageofsuchdrugsshouldnotbetoolarge.Ifthediseaserequiresalargedosage,thedailydosageshouldbedividedinto3times~Give4times.Bytheway,manyantibiotics,suchascephalosporins,vancomycin,tetracycline,nalidixicacid,etc.,cancauseincreasedtoxicandsideeffectsduetodecreasedrenalfunctionandincreasedserumconcentration.Somedrugscanbeusedinreduceddoses,andsomearebestnottobeused,andotherantibioticsareusedinstead.

⒋Therearemanykindsofantibioticsthatcancausedamagetothecentralnervoussystem,suchaspenicillin,cephalosporin,Taineng,aminoglycosides,macrolides,chloramphenicol,polymyxinE,sulfonamides,Somedrugssuchasquinolones,anti-tuberculosisisoniazid,andantiviraldrugs(acyclovir,ganciclovir)cancauseneurologicaldamagetovaryingdegreesandcausevariousbrainsymptoms.

Indications

Picillinisusedforinfectionscausedbysensitivebacteriaorpathogens.Pharyngitis,tonsillitis,scarletfever,endocarditis,erysipelas,cellulitisandpuerperalfevercausedbyhemolyticstreptococcus.Pneumonia,otitismedia,meningitisandbacteremiacausedbypneumococcus.Tetanusandgasgangrenecausedbyclostridium.

1.PenicillinGhasagoodeffectonpharyngitis,scarletfever,cellulitis,septicarthritis,pneumonia,puerperalfeverandsepsiscausedbygroupAβ-hemolyticstreptococcus.Thedrugofchoice.Fortheabovesevereinfections,intravenousdripadministration4timesaday,eachtime1.2millionto1.6millionU.Thetreatmentofpharyngitisshouldbeadministeredforatleast10daystoensurethatthepathogenicbacteriaareeliminatedfromthepharynxtoavoidrheumaticfeverinthefuture.Acutepurulentmeningitis(meningitis)andendocarditiscausedbyStreptococcuspyogenesshouldbeadministeredintravenouslywithhigh-dosepenicillinG(10millionto20millionUperday).

2.Infectionscausedbyotherstreptococci:includingrespiratorytractinfectionscausedbygroupBβ-hemolyticstreptococcus,viridisstreptococcusandfaecalisstreptococcus,acutepurulentmeningitis(meningitis),heartInfectionssuchasendometritisandsepsis.StreptococcuspneumoniaeishighlysensitivetopenicillinG,andpenicillinGtreatmentisthefirstchoice.

3.Meningitiscausedbymeningococcusorothersensitivebacteria:PenicillinGdoesnoteasilypenetratethenormalblood-cerebrospinalfluidbarrierandentersthecerebrospinalfluidinasmallamount,butitispermeabilitywhenthemeningesaredamagedbyinflammationIncrease,sohigh-dosetreatmentiseffective.Thestartingdoseforadultsis10to20millionUperday,dividedinto4intravenousdrips.

4.GonorrhoeacausedbyNeisseriagonorrhoeae:NeisseriagonorrhoeaeissensitivetopenicillinG,butdrug-resistantbacteriahaveincreasedsignificantlyinrecentyears,andsomearehighlyresistant.Therefore,itisnecessarytodecidewhethertousepenicillinGaccordingtotheresultsofthesensitivitytest.Theamountoftreatmentshouldalsobedeterminedbasedonthedegreeofsensitivity.

5.SyphiliscausedbyTreponemapallidum:PenicillinGisstillthemaintreatmentdrug.Forsecondaryandtertiarysyphilisorseverecasesofthefirststage,especiallythosewithearlycentralnervoussystemsymptoms,high-dosepenicillinGshouldbeusedfortreatment,5to20millionUperday,intravenousdrip,3to4weeksoftreatmentStableefficacy.

6.Infectionscausedbygram-positivebacilli:Infectionscausedbytetanus,diphtheria,andanthracisshouldbetreatedwithpenicillinGplusantitoxin.Penicillinismainlyusedindermatologyforthefollowingdiseases:(1)Syphilis.(2)Gonorrhea.(3)Otherssuchasscarletfever,cellulitis,erysipelas,erysipelas,pyoderma,etc.

Usageanddosage

⒈Usualdosageforadults:①Intramuscularinjection,800,000~2millionUperday,administeredin3to4times;②Intravenousdrip,daily2to10millionU,administeredin2to4doses.

⒉Commondosageforchildren:①Intramuscularinjection,25,000U/kg,onceevery12hours.②Intravenousadministration,50,000to200,000U/kgdaily,dividedinto2to4times.

⒊Dosefornewborns:50,000U/kgonce,intramuscularlyorintravenously,onceevery12hoursinthefirstweekofbirth,>onceevery8hourson7days,severeinfectionEvery6hours.

⒋Doseforpreterminfants:30,000U/kginthefirstweek,onceevery12hours,onceevery8hoursin2to4weeks,andonceevery6hoursthereafter.

Preparationsandspecifications

1.Penicillinsodiumforinjection:①0.12g(200,000U);②0.24g(400,000U);③0.48g(800,000U)；④0.6g(1millionU);⑤0.96g(1.6millionU;⑥2.4g(4millionU).

2.Penicillinpotassiumforinjection:①0.125g(200,000U);②0.25g(400,000U);③0.5g(800,000U);④0.625g(1millionU).

Bacterialresistance

StaphylococcusaureusPenicillinismostlikelytoproducedrugresistance.Therearethreemainmechanismsforbacterialresistancetopenicillins:

⒈Bacteriaproduceβ-lactamasetohydrolyzeandinactivatepenicillins

⒉Thetargetsiteofpenicillininbacteria-penicillinbindingproteinchanges

⒊Thepermeabilityofthecellwalltopenicillinsisreduced.

Thefirstmechanismisthemostcommonandthemostimportant.

Picillinantibioticshavegoodwatersolubility,andtheireliminationhalf-lifeismostlylessthan2hours.Theyaremainlyexcretedthroughthekidneys.Mostvarietiescanbeeliminatedbyhemodialysis.

AccordingtotheregulationsoftheChineseMinistryofHealth,useBeforepenicillinantibiotics,apenicillinskintestisrequired.Thosewithapositivereactionareprohibited.

Precautions

⒈Donotmixwithalkalinedrugswhenadministeredorallyorbyinjectiontoavoiddecompositionandfailure.

⒉Thisproductshouldnotbemixedintravenouslywithtetracyclinehydrochloride,kanamycin,polymyxinE,sulfadiazinesodium,adenosinetriphosphate,coenzymeA,etc.toavoidprecipitationorloweringtheeffect.

⒊Chloramphenicolandpenicillinaregenerallynotusedincombination,becausechloramphenicolisabacteriostaticagent,andpenicillinisabactericideinthebreedingperiod,thecombinedusecanaffecttheantibacterialactivityofpenicillinandreducetheeffect.However,thisissueisstillcontroversial.Opinionsdiffer,becausethecombinationofthetwohasagoodclinicaleffectongram-positiveandnegativebacteriamixedinfectionsandintracranialinfections.Thesolution,ifcombineduse,isrecommendedtousepenicillinfor2to3hoursbeforeusingchloramphenicol

⒋Becausetheproductcaninhibittheactivityofcertainliverenzymes,itcaninterferewiththebiotransformationoftolbutamide,phenytoinanddicoumarininthehumanbody,andcanenhancetolsicarbTheeffectofphenytoinsodiumcanenhancetheanticoagulanteffectofdicoumarinandwarfarin.

⒌Usewithcautionininfants,patientswithimpairedliverandkidneyfunction,usewithcautioninlate-pregnancywomen,andbreastfeedingNotforwomen.

Besidestakingaskintestbeforeapplyingpenicillin,youshouldalsopayattentiontothefollowingpoints:

⒈GotoformalmedicalcarewithrescueequipmentTheunitinjectspenicillin,incaseofanallergicreaction,timelyandeffectiverescuetreatmentcanbeobtained.Ifdizziness,palpitation,sweating,breathingdifficultiesandotherdiscomfortoccuratanytimeduringtheinjectionprocess,pleasetellthedoctorandnurseimmediately.

⒉Afterthepenicillininjection,observeinthehospitalforatleast20minutesbeforeleavingwithoutanydiscomfort.

⒊Don’tbeextremelyhungryPenicillinshouldbeusedatthesametimetopreventthebody'stolerancetothedrugfrombeingreducedwhenfasting,whichmayinduceadversereactionssuchasfainting.

⒋Thetwoinjectionsshouldnotbetooclosetoeachother,4-6hoursisbetter.Whenintravenouspenicillinisinstilled,thestartingspeedshouldnotbetoofast.Itisadvisablenottoexceed40dropsperminute.Observethatthereisnoadversereactionfor10-20minutesandthenadjusttheinfusionspeed.

⒌Ifthereisahistoryofpenicillininjectiononthesameday,dizziness,palpitation,sweating,difficultybreathingandotherdiscomfortathome,youshouldbesenttothehospitalfordiagnosisandtreatmentintime.

Sevenpointstopayattentiontoampicillin:

Ampicillin(includingampicillincontainingampicillin,etc.)isthefastestdecomposingandallergicofpenicillindrugsTheonewiththehighestreactionrate,especiallyintheacidicenvironmentandhighbloodconcentration,ismorepronetoallergicdrugeruptionandanaphylacticshockcausedbyampicillindecompositionproductsandstacks,andevenlife-threatening.Whenusingampicillinclinically,notonlydoaskintest,butalsopayattentiontothefollowingpoints:First,anegativeskintestdoesnotmeanthatyouarenotallergic.Allergicreactionstoampicillinaremostlydelayed,andallergicdrugeruptionscanoccurafterseveraldaysofcontinuousmedication,causinganaphylacticshock.Forallergicdrugeruptions,theuseofastemizole,diphenhydramine,anddexamethasonecanberesolvedafterstoppingthedrug.Suddendyspnea,chillsandfever,decreasedbloodpressure,increasedheartrateandothersymptomsshouldbestoppedimmediately,givenoxygen,andrescuedwithepinephrine,dexamethasone,calciumgluconateandotherdrugs.

Second,itissuitableforshort-termuseandavoidlong-termlarge-scaleadministration,soastoavoidthecontinuousincreaseofbloodconcentration,leadingtotheformationandaccumulationofallergensandcausingallergicreactions.

Thirdly,itshouldbeinjectedintravenouslyafterbeingfullydissolvedinasufficientamountofnormalsaline.Generallyspeaking,4gramsofampicillinneedstobedissolvedinabout300mlofnormalsaline(0.9%sodiumchlorideinjection).Itmustnotbedissolvedinsugar,especiallyhypertonicsugar(glucoseinjectionwithaconcentrationgreaterthan5%)forintravenousdrip.Becausesugarisacidic,itcannotonlyreducetheantibacterialandbactericidalabilityofampicillin,butalsopromoteself-decompositionandincreasethechanceofsensitization.

Fourth,patientswithgout,uremia,diabeticketoacidosisandlacticacidosisshoulduseaslittleornoampicillinaspossible.Thereasonisalsothatampicillincanpromoteself-decompositioninacidicenvironmentandincreasethepossibilityofsensitization.

Fifth,thepatientsthemselvesareallergicandshouldbeavoided.

Sixth,itisusuallyadministeredintravenously,whichshouldbeslowratherthanfast,andintravenousdripatarateofnomorethan60dropsperminute,soastopreventthebloodconcentrationfromincreasingtoofastandincreasingthepossibilityofdecompositionandallergies.

Seventh,beforeusing,youshouldfindtheexactevidenceofinfectionbypathogenicbacteriathataresensitivetothisdrug,andavoidblindlymisusingit,soasnottocausefloraimbalanceandmoldinfectionandincreasethedifficultyoftreatment.

Contraindications

Forthosewhoareallergictopenicillinorotherpenicillindrugs.

Beforemedication,thepatientshouldbeaskedwhetherthereisanyhistoryofallergy.Forthosewhohavenotusedpenicillinfor24hours,anintradermalsensitivitytestshouldbeperformed.Thosewithapositivetestresultshouldbedisabled.Peoplewhoareallergictopenicillinorotherpenicillindrugs,andthosewithallergicdiseasesandallergicconditionsshouldnotbeused.

Druginteractions

(1)Combinedusewithprobenecid,aspirin,indomethacinandsulfadrugscanreducetheexcretionofpenicillindrugsandmakepenicillinbloodThedrugconcentrationincreases,theeffectisenhanced,butthetoxicreactionmayalsoincrease.

Probenecidcaninhibitrenaltubularsecretion,thusprolongingthemaintenancetimeofpenicillinbloodconcentration,andhasasynergisticeffectonpenicillin.

(2)Combinedusewithtetracyclines,erythromycin,chloramphenicolandsulfonamidesandotherantibacterialdrugsmayreducetheantibacterialeffectofthisproduct.

Picillinshaveantagonisticeffectswithtetracycline,chloramphenicol,macrolidesandotherantibacterialdrugs.Becausepenicillinisabactericidaldrugduringthereproductionperiod,undertheactionofbacteriostaticdrugs,bacterialreproductionisinhibited,whichmaymaketheeffectofpenicillindrugsinsufficient.

(3)Combinedusewithwarfarincanenhancetheanticoagulanteffect.

(4)Takingcontraceptivesatthesametimemayaffectthecontraceptiveeffect.

(5)Penicillinsandaminoglycosideantibioticshaveasynergisticeffect,buthigh-dosepenicillinGorothersemi-syntheticpenicillinscanreducetheactivityofaminoglycosides.

Drugstandards

Retailpriceinformationofnationalessentialdrugsrelatedtopenicillin

Description:

⒈Theproductsmarkedwith"*"intheremarkscolumnofthetablearerepresentativeproducts.

⒉Inthetable,therepresentativedosageformspecificationismarkedwith"△"intheremarkscolumn,andthepriceoftherepresentativedosageformspecificationandrelatedspecificationswithaclearpricedifferencerelationshipisatemporaryprice.

⒌Doseforpatientswithimpairedrenalfunction:Whentheglomerularfiltrationrate(GFR)is10-15ml/min,thedosingintervalisextendedfrom8hoursto8-12hoursorthedoseisreducedby25%.WhenGFRislessthan10ml/min,theintermittentadministrationis12-18hoursorthedoseisreducedto25%-50%ofthenormaldose.Generallyspeaking,patientswithmildtomoderaterenaldamageshoulduseconventionaldoseswithoutreducingthedose.Forsevererenaldamage,adjustthedoseorextendtheadministrationtime.