第三屆臨床藥師論壇課件

第三屆臨床藥師論壇會(huì)議1.2.藥學(xué)人才在醫(yī)院是非常重要的藥師的地位將越來(lái)越重要藥師將由發(fā)藥向參與臨床合理用藥發(fā)展與藥師相關(guān)的教育：學(xué)校教育與畢業(yè)后教育3.與藥師相關(guān)的制度執(zhí)業(yè)藥師制度（先天不足）繼續(xù)教育制度臨床藥師制度4.臨床藥師制度學(xué)制學(xué)位教育正在研究，50個(gè)臨床藥師基地處于摸索階段，對(duì)臨床藥師的在職培訓(xùn)、能力的標(biāo)準(zhǔn)、培訓(xùn)的內(nèi)容、培訓(xùn)的地點(diǎn)、培訓(xùn)的考核有待于完善。成績(jī)可喜，但剛起步，“醫(yī)藥結(jié)合”合格的臨床藥師隊(duì)伍，從教材開(kāi)始。需要高水平的教材，共22門課程，其中與醫(yī)學(xué)共享7門，獨(dú)立編制15門。5.6.7.臨床藥師責(zé)任要有明確的規(guī)范，職責(zé)會(huì)越來(lái)越多，權(quán)力會(huì)越多，但自身能力不夠，需努力，臨床藥師不是醫(yī)院的“憲兵”，應(yīng)是治療團(tuán)隊(duì)中的一員，形勢(shì)很嚴(yán)峻，但自身素質(zhì)能力需加強(qiáng)，抓住機(jī)遇。8.9.

Drug

Interaction

Pharmacy

WeijianLou10.一、BackgroundPharmacistsandclinicianshavenoticedtheproblemofdruginteraction(DI)sincethebeginningof1960’s.背景藥物學(xué)家和臨床工作者大約在上世紀(jì)60年代初開(kāi)始注意到藥物相互作用的問(wèn)題11.2.《HarwardHealthPublication》March22.2004Boston.MA.

AbouthalfofallAmericansage65andovertakeatleast5medicationsperweek,and1of8take10ormore.Withsomanypeopletakingsomanypills,thereisplentyofopportunityforharmfuldruginteraction…TheFDAmaintainsathoroughsystemforreportingdrugsideeffect,butcurrentlylacksastandardizedmethodforwarningpeopleaboutdruginteraction.

12.3.

Epidemicstudyondruginteractionshows:co-medicationincidencenumber(kind)(%)合用藥物種類co-medicationincidencenumber(kind)(%)合用藥物種類2-5411-15286-101016-205413.4.Objectivereasons:4.1Complicateddiseasesandvariousdrugs.4.2Limitationofnewdrugdevelopingandnewdrugratifying.(ThefullextentofDIpotentialmaybeonlyrecognizedafterthedrugiswidelyavailable.)客觀原因疾病的復(fù)雜性和藥物的多樣性新藥開(kāi)發(fā)和新藥審批的局限性14.5.Currentsituation:5.1lackofdruginteractionknow-ledge.5.2potentialdemandsfordruginteractionknowledge.5.3focusonadversedruginteractionfrompharmaceuticalcarepoint.5.4complicatedDImechanismanddifficultDIprediction,buthavesomemethodstoanalyseit.GenetechnologyhasbeenusedtopredictDI.

現(xiàn)狀藥物相互作用的知識(shí)缺乏對(duì)藥物相互作用的知識(shí)有潛在需求從藥學(xué)服務(wù)的角度主要關(guān)注于不良的藥物相互作用藥物相互作用的機(jī)制非常復(fù)雜并且難以預(yù)料，但有一定的規(guī)律可循?；蚣夹g(shù)已經(jīng)用來(lái)進(jìn)行藥物相互作用的預(yù)測(cè)15.二、DefinitionDrug-druginteractionreferstoalterationoftheeffectofonedrugcausedbythepre-senceofaseconddrug.定義指同時(shí)或前后使用兩種或兩種以上藥物時(shí)，在體內(nèi)產(chǎn)生作用的干擾，或在體外容器內(nèi)就發(fā)生藥物性質(zhì)的改變，結(jié)果使藥物療效發(fā)生量變或質(zhì)變。這些藥物的相互作用，可能是有利的，也可能是有害的。但一般所謂的藥物相互作用都是指兩種或兩種以上的藥物在病人體內(nèi)共同存在時(shí)而產(chǎn)生的一種不良影響。16.三、classification

1.AccordingtoDImechanism:pharmaceutics,pharmacodynomics,pharmacokinetics2.AccordingtoDIproperty:

beneficialor

detrimential(adverse)3.AccordingtotheadverseextentofDI:mild,modest,severe分類

根據(jù)藥物相互作用機(jī)理藥劑學(xué)，藥效學(xué)，藥動(dòng)學(xué)根據(jù)作用性質(zhì)有利的或有害的（不良的）根據(jù)不良的藥物相互作用的程度輕度的,中度的,嚴(yán)重的17.四、DImechanism1.Pharmaceuticmechanism●mainly

dependsonphysicalandchemicalproperty●concentration、PH、temperature、light、osmoticpressure,ect2.Pharmacodynamicmechanism●PharmacodynamicDIsoccurwhendrugwithadditiveorantagonisticpharmaco-dynamiceffectarecombined.●generallyoccurattargetsite藥物相互作用機(jī)理藥劑學(xué)機(jī)理主要是與理化性質(zhì)相關(guān)濃度，PH，溫度，光照，滲透壓等藥效學(xué)機(jī)理藥效學(xué)上具有激動(dòng)或拮抗作用的藥物合用時(shí)通常發(fā)生在靶部位18.3.PharmacokineticMechanism藥動(dòng)學(xué)機(jī)理MechanismeffectTimecoursePrecipitantDrugexampleAbsorption:reducedextentofGIabsorptiondecreasedserumconcentrationofobjectdruginteractionbeginsassoonasthetwodrugsaregiventogetherantacids;kadin-pactin;cholestyramineDistribution:displacementfromplasmaproteinbindingtransientincreaseinfreeserumconcen-trationofoneorbothdrugsbeginsquicklybutusuallydissipatesafterseveraldays,evenifbothdrugscontinuetobegivenoralanticoagu-lants;sulfonamides;phenytion;NSAIDs19.MechanismeffectTimecoursePrecipitantDrugexampleMetabolism(1):enzymeInductionreducedserumconcentrationofobjectdruggradualeffectover1-2weeks.dissipa-tionmaytakeevenlongerbarbiturates;phenytion;rifampin;Metabolism(2):enzymeinhibitionincreasedserumconcentrationofobjectdrugusuallyrapid.Erythromycineffectmaybedelayedbyseveraldays.chlorampheni-cal;isoniazid;cimetidine;sulfonamides;verapamilElemination:reducedrenaldiminationIncreasedserumcon.ofoneorbothdrugsusuallyrapidcephalosporins;probenecid;salicylates20.五.DIclinicstrategy1.PatientshavingagreatriskofDI●theelderlyandthechronicallyill●multipleorgandysfunctions●alongpharmacotherapeuticalprocedure●apatient’sregimenoriginatesfrommultipleprescribers2.DrugshavingagreatriskofDI●warfarin,digoxin,amiodarone,aminophylline

theophylline,phenytoin,erithromycin,fluoroquinolones,ciclosporin,refampin,iosoniazid,ketoconazole,multipleiron-cation(Fe2+、Ca2+,ect)…藥物相互作用臨床策略易引起藥物相互作用的人群患各種慢性疾病的老年人;多器官功能障礙者;需要長(zhǎng)期藥物治療的病人;接受多名醫(yī)生治療的病人易引起藥物相互作用的藥物華法林、地高辛、乙胺碘呋酮、氨茶堿、茶堿、苯妥英鈉、紅霉素、喹諾酮類、環(huán)孢素、利福平、異煙肼、酮康唑、多價(jià)金屬陽(yáng)離子……21.3.Knowallthepatient’sdrugs4.MakeuseofthecurrentreferencematerialsandthecomputerizedDIwarningsystem5.Trytouselessdrugsifpossible6.DIclinicdetermination●absolutelyprohibited●relativelyprohibited●precaution●attention

7.ManyDIproblemscanberesolvedbyrelevantadjustment

了解病人使用的所有藥物利用當(dāng)前的參考資料和DI軟件系統(tǒng)盡可能少地合用藥物藥物相互作用的臨床判定絕對(duì)禁止;相對(duì)禁止;注意事項(xiàng);引起重視;許多藥物相互作用的問(wèn)題可以通過(guò)相應(yīng)的調(diào)整得到解決22.六.DIcases1.levodopa+carbidopa●

Levodopaisanorally-availableprecursorofdopamine.

●carbidopaisaperipheralDOPAdecarboxylaseinhibitor.藥物相互作用實(shí)例左旋多巴+甲基多巴肼左旋多巴是一種口服多巴胺前體藥物甲基多巴肼是一種外周多巴脫羧酶抑制劑磺胺甲口惡唑+甲氧芐肼2.sulfamethoxazole+trimethoprimSMZTMP

(—)(—)PABAdihydrofolicacidtetrahydrofolate（對(duì)氨基苯甲酸）（二氫葉酸）（四氫葉酸）23.

3.

Cefoperazone+SulbactamSodium●Cefoperazoneisathird-generationcephalosporinantibiotic.●

SulbactamSodiumisanirreversibleinhibitorofbeta-lactamases.

4.

Cyclophosphamideandmesna.

●Themetabolitesofcyclophosphamide,includingacrolein,consideredtoberesponsibleforthetoxiceffectsonthebladder.●Mesnahasthiolgroupsthatreactwiththemetabolites.頭孢哌酮+舒巴坦鈉頭孢哌酮是第三代頭孢類抗生素;舒巴坦鈉是不可逆的 ?-內(nèi)酰胺酶抑制劑環(huán)磷酰胺和美司鈉環(huán)磷酰胺的代謝物包括丙烯醛，與其膀胱毒性密切相關(guān);美司鈉中的巰基能與其代謝物發(fā)生反應(yīng)24.5.TPN:●

Ca++concentration●aminoacids●themixingprocedure6.Oxaliplatine●Donotmixwithotherdrugs,maybedegradedoncontactwithalumiun.●shouldnotbereconstitutedwithNS

7.Omeprazole●shouldbereconstitutedwiththespecialsolvent8.Amoxycillinsodiumclavulanatepotassium

●shouldnotbereconstitutedwithGSTPN

鈣離子濃度氨基酸配制過(guò)程奧沙利鉑

不能與其他藥物相混，遇到鋁會(huì)分解失活;不能用生理鹽水稀釋奧美拉唑必須用其特制溶媒稀釋阿莫西林鈉克拉維酸鉀不能用葡萄糖水稀釋25.9.PotassiumChloridemixture＆antidiabeticagents●Potassiumchloridemixtureincludes50%ofglucose.10.

Loratadine＆PPDskintest●Antihistaminesmaysuppresspositiveskintestresultsandshouldbestoppedseveraldaysbeforethetest.11.CALTRATE

D＆levothyroxine●calciumsupplementsaretakenatthesametimewithlevothyroxine,lessofthedrugsmaybeabsorbed

12.Forlax＆oraldrugs●Highmolecularweightweight(4000)macragolsarelongpolymerswhichretainwatermoleculesbymeansofhydrognbondsandwillcoattheoraldrugsandpreventtheabsorptionoftheoraldrugs.

氯化鉀合劑和降糖藥

氯化鉀合劑含有50%葡萄糖氯雷他定和PPD試驗(yàn)

抗組胺藥物可以抑制皮試陽(yáng)性反應(yīng)必須在做皮試之前幾天停用鈣爾奇和左旋甲狀腺素鈣劑和左旋甲狀腺素同時(shí)服用可以降低藥物的吸收福松和口服藥物福松會(huì)包裹口服的藥物阻止其從腸道吸收26.13.Levofloxacinhydrochloridecapsules＆Ferroussuccinatetablets●decreasetheabsorptionofbothdrugs14.pentoxifyllinesustainedreleasetablets＆antihypertivedrugs●pentoxifyllinemaypotentiatetheeffectofantihypertensiveagents15.theophylline＆cifranhydrochloride●theophylline:anarrowtherapeuticrange●cifran:mayenhancetheserumconcentrationoftheophylline16.colloidalbismuthpectincapsules＆PPI●CBPneedsanacidicenvironment●PPIisangastricacidsecretioninhibitor左氧氟沙星片和琥珀酸亞鐵片

兩者的吸收都減少己酮可可堿緩釋片和抗高血壓藥物己酮可可堿可增加抗高血壓的作用茶堿和悉復(fù)歡茶堿的治療窗比較窄悉復(fù)歡可以提高茶堿的血漿濃度膠體果膠鉍和質(zhì)子泵抑制劑CBP需在酸性環(huán)境中發(fā)揮作用質(zhì)子泵抑制劑是胃酸分泌的抑制劑27.17.CalciumGluconateforinjection＆Digoxin●Ca++increasesthecardiologictoxicityofdigoxin18.Digoxin＆Neb1%Ephedrine

●maycauseseverearrhythmia

19.Lithium＆ACEIorNSAIDs

●lithiumtoxicityiscloselyrelatedtoserumlevelsandcanoccurattherapeuticdoses.●medicationswhichaltersodiumexcretion(ACEI、NSAIDs)willenhancetheserumconcentrationoflithium20.LipobayIncident(lipobay+brates)●theriskofrhabdomyolysisincreases21.NSAIDs+ACEI●maydecreasetheeffectivenessofACEI葡酸鈣注射液和地高辛