《藥學導論》1緒論-zhuliang

藥理學

Pharmacology

朱亮上海交通大學醫(yī)學院1精選課件

藥物（Drug）定義影響機體生理功能或生化過程,用于預防、診斷、治療疾病或用于計劃生育的物質Achemicalwhichisutilizedforthediagnosis,prevention,

cureoralleivationofanunwantedhealthcondition2精選課件藥物在醫(yī)學中的地位內/外/婦/兒神經(jīng)循環(huán)消化…病因/機制

診斷

治療

藥物治療

其他治療手段

3精選課件SourceofdrugsAncient–NaturalproductsPlantsAnimalsMineralsModernActiveprinciplesofnaturalproductsArtificialsynthetics

FullsyntheticSemi-syntheticProductsofgeneticengineering精選課件DrugSources基因工程藥物過程示意圖①從細胞中分離出DNA①③④⑥②限制酶截取DNA片斷③分離大腸桿菌中的質粒④DNA重組⑤用重組質粒轉化大腸桿菌⑥培養(yǎng)大腸桿菌克隆大量基因6精選課件BacteriaMicroorganismstoproducesimplechemicalsformanufactureprocessMicroorganismstoproducefulllengthpolypeptidesBacteriaproducehumaninsulin“PharmAnimals”TransgenicSheepcarrygeneforhumanFactorIXCowsthatproducehumanantibodiesExampleProductionMethods精選課件現(xiàn)代生物藥突飛猛進biopharmaceutical/biologicalmedicalproduct/biologic/biologicalmanufacturedinorextractedfrom

biologicalsources.distinctfrom

chemically

synthesizedpharmaceuticalproducts.include

vaccines,

blood

orbloodcomponents,allergenics,genetheraphies,tissues,

recombinanttherapeuticprotein

andlivingcells.精選課件2014全球暢銷藥物Mannsetal.Sofosbuvir:thefinalnailinthecoffinforhepatitisC?LancetInfectDis20159精選課件與藥物相關的概念藥物，藥品，毒物，毒品Drug,Medicine,Poison,Toxin,Narcotics10精選課件藥品用于預防、治療、診斷人的疾病，有目的地調節(jié)人的生理功能并規(guī)定有適應證、功能主治和用法用量的物質，包括中藥材、中藥飲片、中成藥、化學原料藥及其制劑、抗生素、生化藥品、放射性藥品、血清疫苗、血液制品和診斷藥品等?！吨腥A人民共和國藥品管理法》（主席令第45號）201111精選課件DrugandMedicine(andnarcotics)Drug

……Ineverydayparlance,theworddrugisoftenassociatedwithaddictive,narcoticormind-alteringsubstances-anunfortunatenegativeconnotationthattendstobiasopinionagainstanyformofchemicaltherapy.MedicineAmedicineisachemicalpreparation,whichusuallybutnotnecessarilycontainsoneormoredrugs,administeredwiththeintentionofproducingatherapeuticeffect.Medicinesusuallycontainothersubstances(excipients,stabilisers,solvents,etc.)besidestheactivedrug,tomakethemmoreconvenienttouse.Tocountasadrug,thesubstancemustbeadministeredassuch,ratherthanreleasedbyphysiologicalmechanisms.Manydrugsarenotusedinmedicinesbutareneverthelessusefulresearchtools.12精選課件毒物POISONpoisonsaredrugthathavealmostexclusivelyharmfuleffectsandfallstrictlywithinthedefinitionofdrugs.However,Paracelsus(1493–1541)famouslystatedthat"thedosemakesthepoison,"meaningthatanysubstancecanbeharmfuliftakeninthewrongdosage.

TOXINToxins

areusuallydefinedaspoisonsofbiologicorigin,ie,synthesizedbyplantsoranimals,incontrasttoinorganicpoisonssuchasleadandarsenic13精選課件藥物or毒物食物氯化鈉水藥物補液毒物高鈉血癥高血壓藥食同源，藥毒難分All

substancescanundercertaincircumstancesbetoxic,andthechemicalsinbotanicals(herbsandplantextracts)arenodifferentfromchemicalsinmanufactureddrugsexceptfortheproportionofimpurities(greaterinbotanicals)精選課件問題何為藥物，何為毒物？兩者有何種聯(lián)系？現(xiàn)實中對兩者如何區(qū)別？能否舉出兩者間關系的典型事例？藥物-毒物關系理論對臨床和科研有何指導意義？滬府發(fā)[2015]12號《上海市人民政府關于表彰2014年度上海市科學技術獎獲獎人員（項目）的決定》…授予“髓系白血病發(fā)病機制和新型靶向治療研究”項目特等獎君：砷劑臣：丹參酮佐：靛玉紅15精選課件16精選課件DrugNamingChemicalnameascientificnamethatpreciselydescribesitsatomicandmoleculardescribechemicalstructure(rarelyseeninmedicalliterature)CodeNameshortletter-numbercombinationusedforexperimentaldrugsGeneric/nonproprietarynameanabbreviationofthechemicalnameanameassignedtodrugthatcanbeusedbyanyoneTrade/brand/proprietarynameProprietarynamegiventothedrugbythemanufacturer3,3-二甲基-7-氧代-6-[(苯乙?；?氨基]-4-硫雜-1-氮雜二環(huán)[3.2.0]庚烷-2-羧酸單鈉鹽17精選課件通用名：國際非專有名稱，全球通用，是國家藥典或藥品標準采用的法定名稱。不論何處生產的同種藥品都可用的名稱。商品名/品牌名：又稱為商標名，具有企業(yè)專屬性，受到法律的保護，常在右上角標示?。習用名：又稱為別名、是不規(guī)范的名稱，但由于一定歷史原因曾在一段時間長期廣泛應用。國食藥監(jiān)注[2006]99號《關于進一步規(guī)范藥品名稱管理的通知》中華人民共和國衛(wèi)生部令第53號《處方管理辦法》（2007）18精選課件通用名 習用名頭孢氨芐 先鋒4號諾氟沙星 氟哌酸鹽酸小檗堿 黃連素對乙酰氨基酚 撲熱息痛吲哚美辛 消炎痛吡羅昔康 炎痛喜康19精選課件藥理學(Pharmacology)Pharmacologyisthescienceofstudyingtheeffectofdrugsonlivingorganisms.

Scientificstudyoftheinteractionsbetweendrugsandthebody20精選課件藥理學

研究藥物與機體(病原體)相互作用及作用規(guī)律的學科

既研究藥物效應動力學

也研究藥物在機體的影響下所發(fā)生的變化及規(guī)律21精選課件藥物效應動力學（Pharmacodynamics）藥物代謝動力學（Pharmacokinetics）作用、作用機制吸收、分布、代謝、排泄22精選課件血液循環(huán)示意圖精選課件藥物效應動力學-Whatadrugdoestothebody

藥物對機體的作用及作用機制藥物代謝動力學-Whatthebodydoestoadrug機體對藥物的處置、轉運、轉化ADME過程藥物濃度隨時間變化的規(guī)律Pharmacodynamicsgovernstheconcentration-effectpartoftheinteraction,whereaspharmacokineticsdealswiththedose-concentrationpart(Holford&Sheiner,1981).24精選課件藥理學研究內容藥效學藥理作用作用機制臨床應用不良反應藥動學體內過程時量關系消除動力學及相關參數(shù)穩(wěn)態(tài)血藥濃度藥物相互作用25精選課件藥理學是橋梁學科基礎醫(yī)學臨床醫(yī)學藥理學藥學醫(yī)學生物學26精選課件教育部學科分類10醫(yī)學1001基礎1002臨床1003口腔1004公衛(wèi)1005中醫(yī)1007藥學100701藥化100702藥劑100703生藥100704藥分100705生物藥100706藥理07理學0780藥學078006藥理學精選課件“三段式”體系下的藥理學課程安排學期23456-臨床細胞生物

解剖

組胚

生理

生化

免疫微生物

寄生蟲

病理

病生

遺傳

藥理

28精選課件“器官系統(tǒng)”體系下的藥理學學期（5or8年制）2or33or44or55or6人體構造

分子細胞組織

代謝能量

遺傳發(fā)育

防御免疫

病理病生總論

病原生物

藥理學總論

神經(jīng)系統(tǒng)

循環(huán)系統(tǒng)

消化系統(tǒng)

呼吸系統(tǒng)

血液系統(tǒng)

泌尿系統(tǒng)

內分泌系統(tǒng)

29精選課件指導臨床合理用藥闡明機體生命現(xiàn)象研究開發(fā)新藥藥理學的學科任務30精選課件藥理學與諾貝爾獎王來有2008西北醫(yī)學教育31精選課件藥理學的形成和發(fā)展

(HistoricalHighlights)32精選課件1．藥物學階段33精選課件古埃及、巴比倫、印度1500BC,埃及,亞伯斯古醫(yī)籍(Eberspapyrus)1500BC，印度草醫(yī)學，100BC~100用梵語編撰草藥方劑34精選課件“神農本草經(jīng)”(ShengNong’sHerbalClassic)中國2700BC，草藥方劑治病漢代正式編撰“神農本草經(jīng)”

（大約公元一世紀成）載藥365種，不少流傳至今，如人參、甘草、當歸、麻黃、大黃歷代均有修訂、增補，愈臻完善35精選課件歷27年,明末1578年完成52卷,190萬字收藥1892種 插圖1160幅藥方11000條英、日、德、俄、法、拉丁7種文字“本草綱目”（CompendiumofMateriaMedica)李時珍36精選課件Materiamedicathescienceofdrugpreparationandthemedicaluseofdrugstheprecursortopharmacology.37精選課件2．藥理學形成階段38精選課件18世紀末生理學和化學學科的發(fā)展為現(xiàn)代藥理學發(fā)展奠定基礎Inthelate18thandearly19thcenturies,Fran?oisMagendie,andlaterhisstudentClaudeBernard,begantodevelopthemethodsof

experimentalphysiology

and

pharmacology.1806年德國藥劑師FredrickSerturner(1783-1841)從罌粟中分離出嗎啡。純化合物的出現(xiàn)使能重復定量給藥，從而產生科學藥理學.Initsbeginnings,beforetheadventofsyntheticorganicchemistry,pharmacologyconcerneditselfexclusivelywithunderstandingtheeffectsofnaturalsubstances,mainlyplantextracts-andafew(mainlytoxic)chemicalssuchasmercuryandarsenic.Thepurifiedcompoundsshowedthatchemicals,notmagicorvitalforces,wereresponsiblefortheeffectsthatplantextractsproducedonlivingorganisms。39精選課件阿托品

(atropine;d,l-hyoscyamine)Atropos:goddessesoffateanddestinytheoldestoftheThreeFates,andwasknownasthe"inflexible"or"inevitable."ItwasAtroposwhochosethemechanismofdeathandendedthelifeofeachmortalbycuttingtheirthreadwithher"abhorredshears.“精選課件嗎啡morphine詞根來源“Morpheus”,意為“夢神”,被稱為“God’sownmedicine”41精選課件Advancesinchemistryandthefurtherdevelopmentofphysiologyinthe18th,19th,andearly20thcenturieslaidthefoundationneededforunderstandinghowdrugsworkattheorganandtissuelevels.42精選課件RudolfBuchheim(1820–1879)foundedthefirstinstituteofpharmacologyattheUniversityofDorpat(Tartu,Estonia)in1847,usheringinpharmacologyasanindependentscientificdiscipline.OswaldSchmiedeberg(1838–1921),togetherwithhismanydisciples(12ofwhomwereappointedtochairsofpharmacology),helpedtoestablishthehighreputationofpharmacology.Fundamentalconceptssuchasstructure-activityrelationship,drugreceptor,andselectivetoxicityemergedfromtheworkof,respectively,T.Frazer(1841–1921)inScotland,J.Langley(1852–1925)inEngland,andP.Ehrlich

(1854–1915)inGermany.AlexanderJ.Clark(1885–1941)inEnglandfirstformalizedreceptortheoryintheearly1920sbyapplyingtheLawofMassActiontodrug-receptorinteractions.43精選課件44精選課件“藥物發(fā)現(xiàn)”標志性事件16thcentury——Diethylether1799,mid-19thcentury——nitrousoxide1859——Amylnitrite1853,1897——AspirinBeginninginthe20thcentury——barbituratesandlocalanaesthetics1909——arsenicalcompoundsfortreatingsyphilis45精選課件1935——sulfonamidesBeforeandduringtheSecondWorldWar——penicillin............46精選課件中國藥理學家在麻黃堿嗎啡鎮(zhèn)痛作用部位青蒿素研究方面做了重要貢獻47精選課件新藥開發(fā)藥品：加工成某一劑型，并規(guī)定有適應證、用法及用量的藥物。藥品是特殊的商品，受到法律嚴格規(guī)范管制。精選課件新藥化學品新藥“未曾在中國境內上市銷售的藥品”；已上市藥品改變劑型、改變給藥途徑，亦按照新藥管理。中藥、天然藥物新藥“未在國內上市銷售的從植物、動物、礦物等物質中提取的有效成分及其制劑”生物制劑《藥品注冊管理辦法》局令第28號（2007年）精選課件新藥的研究與開發(fā)Newdrugresearchanddevelopment藥學

理化性質工藝路線質量標準臨床前研究臨床研究藥效學藥動學毒理學臨床試驗Ⅰ期Ⅱ期Ⅲ期Ⅳ期50精選課件“反應停”致海豹肢畸形兒事件1953年，瑞士Ciba藥廠合成了一種thalidomide（沙利多胺，反應停）ThisdrugwasmarketedbytheGermanyfirmChemieGrünenthalasasafealternativetobarbituratehypnotics,especiallyforpregnantwomenonOctober1,195751精選課件52精選課件53精選課件InPhaseItrials,researcherstestanewdrugortreatmentinasmallgroupofpeople(20-80)forthefirsttimetoevaluateitssafety,determineasafedosagerange,andidentifysideeffects.InPhaseIItrials,thestudydrugortreatmentisgiventoalargergroupofpeople(100-300)toseeifitiseffectiveandtofurtherevaluateitssafety.InPhaseIIItrials,thestudydrugortreatmentisgiventolargegroupsofpeople(1,000-3,000)toconfirmitseffectiveness,monitorsideeffects,compareittocommonlyusedtreatments,andcollectinformationthatwillallowthedrugortreatmenttobeusedsafely.InPhaseIVtrials,postmarketingstudiesdelineateadditionalinformationincludingthedrug'srisks,benefits,andoptimaluse.ClinicalTrials精選課件新藥臨床試驗各期特點55精選課件56精選課件合成篩選TheLongRoadtoaNewMedicineI期臨床試驗II期臨床試驗III期臨床試驗臨床前安全有效性藥物制劑候選化合物初步安全有效性研究設計申請證書上市ProcessofDrugDevelopment

57精選課件HighRiskProcess:11-15Years,$1B+臨床前藥理學臨床前毒理學篩選數(shù)百萬化合物IdeaDrug11-15Years1–2產品PhaseIPhaseIIPhaseIII015510臨床藥理學和毒理學~100設計方案Pre-clinical58精選課件59精選課件60精選課件61精選課件Highrisk,highreturnDevelopmentofnewdrugsisenormouslyexpensive,andtosurviveandprosper,bigpharmamustpaythecostsofdrugdeve