penicilin

Úvod ke sloučenině

Základní informace

Čínský název:penicilin

Čínština:penicilin

Anglický název:benzylpenicilin

Angličtina:cilloral;pradupen;Ursopen;benzylpenicilin;cosmopen;

Číslo CASN:61-33-6

Molekulární vzorec:C₁₆H₁₈N₂O₄S

Molekulární hmotnost: 334,39000

Přesná hmotnost: 334,09900

PSA:112,01000

LogP:1,18960

Fyzikální a chemické vlastnosti

Hustota: 1,42 g/cm³

Bod varu: 663,3ºCat 760 mmHg

Bod vzplanutí: 355ºC

Index lomu: 1,655

Skladovací podmínky: větrané, nízkoteplotní a suché

Bezpečnostní informace

Customscode:32041900

WGKNěmecko:2

Kód kategorie nebezpečí:R42/43

Bezpečnostní pokyny: S36/37

Číslo RTECS:XH9700000

Značka nebezpečného zboží: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.

V roce 1938 německý chemik ErnstChannsaw Fleming vytvořil sešity a začal s experimenty s čištěním.

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".

V roce 1945 použil britský chemik D.C.Hodgkin rentgenovou difrakci k určení molekulární struktury penicilinu.

5. září 1944 se zrodila první várka podomácku vyráběných penicilinů v Číně, čímž byla odhalena historie čínské výroby antibiotik. Koncem roku 2001 představovala čínská roční produkce penicilinu 60 % světového celkového ročního počtu penicilinů.

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.

Podle jejích charakteristik jej lze rozdělit na:

PenicilinG:jako je spenicilin, draslík, penicilin, sodík, dlouhodobě působící cilin, penicilin, penicilin, penicilin, penicilin sodný, benzylpenicilin sodný, penicilin draselný, benzylpenicilin draselný atd.

PenicilinV:(také znám jako:fenoxymethylpenicilin,6-fenoxyacetamidopenicilanová kyselina)suchaspenicilinVdraslík (včetně různých lékových forem)).

Penicilin rezistentní na enzymy:suchasoxacilin (XinqingII), chlorazolepenicilin atd.

Ampicilin:suchasampicilin, amoxicilin atd.

Anti-pseudomonaspenicilin:jako karbenicilin, piperacilin, tikarcilin atd.

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

Methiciliny:suchastamoxicilin atd.

Metoda přípravy

Metoda výroby přírodního penicilinu a polosyntetického penicilinu je zcela odlišná.

[Přírodní penicilin]

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).

[Semisyntetický penicilin]

Using6APAasanintermediateandavarietyofchemicallysynthesizedorganicacidsforacylationreaction,varioustypesofSemi-syntheticpenicillin.

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

[Metoda koncentrace penicilinu]

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. Penicilin nelze kombinovat s podobnými antibiotiky

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

2. Penicilin nelze použít v kombinaci se sulfadry a tetracykliny

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

3. Penicilin nelze smíchat s aminoglykosidovými léky pro infuzi

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,linkomycin,tetracyklin,vankomycin,erythromycinethylsukcinát,amfotericinB,norepinefrin,meta-hydroxylamin,fenytoinsodný,hydroxyhydrochloridsečtenotopenicilinvnitrožilníinfuzi.při infuzi léku se při infuzi léku po oxazinu,protaminu,protaminu,protaminu objeví po oxazinu,protaminu,vitaminu etheru, etheru,protaminu

⒏Penicilin může zvýšit účinek warfarinu.

⒐Aftertheproductismixedwithaminoglycosideantibiotics,theantibacterialactivityofthetwodrugsissignificantlyweakened,sothetwodrugscannotbeadministeredinthesamecontainer.

Drogová toxicita

Penicilinová alergie

Je rychle absorbován po podání, asi 75 % ～ 90 % se může vstřebat z gastrointestinálního traktu. Potraviny nemají významný vliv na vstřebávání léků. Jeho rychlost vázání bílkovin je 17 %-20 % a poloviční rozpadové období eliminace krve do 8 léku (t1/2 hodiny) je přibližně 4 % za 6 % za 6 % z 1. % dávky se vylučuje močí jako prototyp léku a některé léky se vylučují žlučovým traktem. Tento poločas života pacientů se závažnou nedostatečností ledvin lze prodloužit na 7 hodin. Sérová dialýza může odstranit penicilin, ale peritoneální dialýza nemá žádný vliv na odstranění produktu.

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.

Princip propadu

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.Veterinární klinické alergie jsou obecně mírné, většinou se projevují jako pocení, vzrušení, neklid, svalový třes, dušnost, zrychlený srdeční tep, nestabilní stav, někdy třesavka, otoky očních víček a obličeje, vulvy a otoky konečníku a septická celulitida, v každém případě šok

[Příčina]

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

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

[První opatření]

⒈Okamžitě zastavte léčbu, lehněte si a zachraňujte na místě, s hlavou a stehny.

⒉Subkutánní injekce 0,1% epinefrinhydrochloridu 0,5–1 ml, děti jej mohou snížit, a poté subkutánní injekce 0,5 ml každou půlhodinu, až do rizikového období, přidat kortikosteroidy nebo antihistaminika, pokud je to nutné.

⒊Patientswithcardiacarrestshouldundergocardiacchestcompressionorintracardiacinjectionof0.1%epinephrinehydrochloride1ml.

⒋Oxygeninhalation,mouth-to-mouthartificialrespirationwhenbreathingisinhibited,andintramuscularinjectionofnicotinicacidorlobelineandotherrespiratorystimulants.

Laryngealedemaaffectsthetracheotomyduringbreathing.

⒌Použijte hydrokortison 200 mg, nebo dexamethason 5-10 mg na 50% glukózu 40 ml nitrožilní injekci, nebo 5-10 % glukózu 500 ml nitrožilně.

⒍Vasoaktivní léky, jako je dopamin, alamin atd., lze použít podle potřeby onemocnění.

⒎Correctacidosisandtheapplicationofhistaminedrugs.

⒏Udržujte se v teple, zabraňte nachlazení, veďte záznamy a nehýbejte se.

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

⒑MoxamoxibustioncanbeusedatacupointssuchasNeiguan,Hegu,Yongquan,Guanyuan,andZhongwan.

Penicilinencefalopatie

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.

V důsledku poklesu renální funkce u starších pacientů má penicilin a další širokospektrální peniciliny prodloužený poločas?Například penicilinGintravenózně má poločas života 0,55 u 25letého člověka. roční děti;dicloxacilinové méně než 30 let Poločas rozpadu je 0 .88 hodin a je 3,97 hodin u starších starších nad 65 let;poločas rozpadu famoxicilinu je 1 hodina až 1,5 hodiny u mladých lidí a 2,67 hodin u starších lidí. vázaný stav a jejich volná část stoupá v krvi a tkáních. Když starší lidé používají velké dávky penicilinu a karbenicilinu, mohou se objevit neurologické až psychiatrické příznaky, jako je hyperreflexie, poruchy vnímání, halucinace, křeče, letargie atd. .,stejně jako dočasné duševní poruchy,proneto"penicilinencefalopatie".

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.

Komalasty po dlouhou dobu a mohou mít vážné následky. Tyto následky mohou zahrnovat otupělost, slepotu, hluchotu, ochrnutí atd. Malý počet pacientů může zemřít na vážné onemocnění.

[Léčba]

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.

[Opatření]

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.

⒋Existuje mnoho druhů antibiotik, která mohou způsobit poškození centrálního nervového systému, jako je spenicilin, cefalosporin, Taineng, aminoglykosidy, makrolidy, chloramfenikol, polymyxinE, sulfonamidy, některá léčiva, jako jsou léky, užívané jako chinolony, anti-tuberkulózní a infekční viróza, viróza proti tuberkulóze

Indikace

Piciliny se používají u infekcí způsobených citlivými bakteriemi nebo patogeny. Faryngitida, angína, šarla, endokarditida, erysipel, celulitida a puerperální horečka způsobené hemolytickým streptokokem.

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.Infekce způsobené grampozitivními bacily:Infekce způsobené byetanem, záškrtem a antracisem by se měly léčit penicilinem G plus antitoxinem.

Použití a dávkování

⒈Obvyklé dávkování pro dospělé:①Intramuskulární injekce, 800 000 ~ 2 miliony denně, podáno 3 až 4krát; ②Intravenózní kapání, denně 2 až 10 milionů U, podáno 2 až 4 dávky

⒉Běžná dávka pro děti:①Intramuskulární injekce,25 000 U/kg, jednou za 12 hodin.②Intravenózní podání, 50 000 až 200 000 U/kg denně, rozděleno 2 až 4krát.

⒊Dávka pro novorozence: 50 000 U/kgonce, intramuskulárně nebo intravenózně, jednou za 12 hodin v prvním týdnu narození,> jednou za 8 hodin za 7 dní, závažná infekce Každých 6 hodin.

⒋Dávka pro předčasně narozené děti: 30 000 U/kg v prvním týdnu, jednou za 12 hodin, jednou za 8 hodin za 2 až 4 týdny a poté jednou za 6 hodin.

Přípravky a specifikace

1. Penicilinsodík pro injekci:①0,12 g (200 000 U);②0,24 g (400 000 U);③0,48 g (800 000 U)； 9④0,6 g (0,6 milionu U); 1,6 milionu U;⑥2,4 g (4 miliony U).

2. Penicilin draselný pro injekci:①0,125 g (200 000 U);②0,25 g (400 000 U);③0,5 g (800 000 U);④0,625 g (1 milion U).

Bacterialresistance

StaphylococcusaureusPenicillinismostlikelytoproducedrugresistance.Therearethreemainmechanismsforbacterialresistancetopenicillins:

⒈Bacteriaproduceβ-lactamasetohydrolyzeandinactivatepenicillins

⒉Thetargetsiteofpenicillininbacteria-penicillinbindingproteinchanges

⒊Thepermeabilityofthecellwalltopenicillinsisreduced.

Thefirstmechanismisthemostcommonandthemostimportant.

Picillinantibioticshavegoodwatersolubility,andtheireliminationhalf-lifeismostlylessthan2hours.Theyaremainlyexcretedthroughthekidneys.Mostvarietiescanbeeliminatedbyhemodialysis.

AccordingtotheregulationsoftheChineseMinistryofHealth,useBeforepenicillinantibiotics,apenicillinskintestisrequired.Thosewithapositivereactionareprohibited.

Bezpečnostní opatření

⒈Při perorálním podávání nebo injekčním podáváním nemíchejte s alkalickými léky, abyste zabránili rozkladu a selhání.

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.

Kromě testu kůže před aplikací penicilinu byste měli věnovat pozornost následujícím bodům:

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.

Sedmibodové zastavení ampicilinu:

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.

Za páté, pacienti sami jsou alergičtí a je třeba se jim vyhnout.

Sixth,itisusuallyadministeredintravenously,whichshouldbeslowratherthanfast,andintravenousdripatarateofnomorethan60dropsperminute,soastopreventthebloodconcentrationfromincreasingtoofastandincreasingthepossibilityofdecompositionandallergies.

Seventh,beforeusing,youshouldfindtheexactevidenceofinfectionbypathogenicbacteriathataresensitivetothisdrug,andavoidblindlymisusingit,soasnottocausefloraimbalanceandmoldinfectionandincreasethedifficultyoftreatment.

Kontraindikace

Pro alergickou alergii nebo jiné penicilinové léky.

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

Drogové interakce

(1)V kombinaci s probenecidem, aspirinem, indometacinem a sulfadry může snížit vylučování penicilinových léků a způsobit penicilinovou krev Koncentrace léku se zvýší, účinek se zvýší, ale toxická reakce se může také objevit.

Probenecidcaninhibitrenaltubularsecretion,thusprolongingthemaintenancetimeofpenicillinbloodconcentration,andhasasynergisticeffectonpenicillin.

(2)Combinedusewithtetracyclines,erythromycin,chloramphenicolandsulfonamidesandotherantibacterialdrugsmayreducetheantibacterialeffectofthisproduct.

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

(3) Kombinované použití s ​​warfarem může zvýšit antikoagulační účinek.

(4)Užívání antikoncepce ve stejnou dobu může ovlivnit antikoncepční účinek.

(5)Penicillinsandaminoglycosideantibioticshaveasynergisticeffect,buthigh-dosepenicillinGorothersemi-syntheticpenicillinscanreducetheactivityofaminoglycosides.

Lékové standardy

Informace o maloobchodních cenách národních základních léků souvisejících s topenicilinem

Popis:

⒈Produkty označené"*"ve sloupci značek v tabulce jsou reprezentativní produkty.

⒉Inthetable,therepresentativedosageformspecificationismarkedwith"△"intheremarkscolumn,andthepriceoftherepresentativedosageformspecificationandrelatedspecificationswithaclearpricedifferencerelationshipisatemporaryprice.

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