1PHARMACOLOGYacetaminophenchlorpheniraminemaleatePseudoephedrinecaffeineConstituent：Anti-coldformulasfeverSneeze,SnivelNasalobstruction2SevenSectionsSection1BasicPrinciplesSection2PharmacologyofEfferentNervousSystemSection3PharmacologyofCentralNervousSystem

Section4PharmacologyofGutSystemSection5PharmacologyofEndocrineSystemSection6PharmacologyofChemotherapeutics

Section7Pharmacologyofanti-cancerdrugsandImmuneSystemContents3SectionI.Basic(General)Principles

Chapter1.Preface1.ThenatureanddutiesofPharmacology2.HistoryandDevelopmentofPharmacology3.MethodologyofLearningPharmacology4.PharmacologyinNewDrugR&D4Chapter1Preface

TheNatureandDutiesofPharmacology

Pharmacology（藥理學(xué)）---Tostudytheprinciplesofinteractionsbetweendrugandlivingsystemwhichincludeshumanbody,tumorcellsandmicroorganismsanditsmechanisms.5

Drug(medicine）---Chemicalsubstances(exogenousorendogenoussubstancese.g.,syntheticdrugs,hormones,antibiotics,peptides,andDNAfragments,etc.)usedtotreat,prevent,diagnosediseasesandcontrolbirth.WesternDrug(chemicals):morphine;aspirin;interferonTraditionalChineseMedicine:Fromplants,animalsormineralsubstances6

Poison(toxicant)Chemicalsubstancestoharmorinjurehumanhealthinsmalldose.

Toxinsareusuallydefinedaspoisonsofbiologicorigin,i.e.,synthesizedbyplantsoranimals,incontrasttoinorganicpoisonssuchasleadandarsenic.7

Drugandpoison:nobasicdifference,theoverdoseofdrugcanbecomethepoison.Sometimes,poisoncanbeusedasadruginsuitabledose,suchastoxinsfromplantoranimals(snakevenom).Drugmaybeapoisonwhenuseoverdoseorlongtermuse.e.g.,Barbituratesusuallyusedassleepingdrug,whenuseoverdoseitmaycauseintoxication.8TheMainPartsofPharmacologya.Pharmacodynamics

(藥物效應(yīng)動(dòng)力學(xué)，藥效學(xué))

Drug≒Bodyb.Pharmacokinetics(藥物代謝動(dòng)力學(xué)，藥動(dòng)學(xué))

9Toexplainthebiochemicalorphysicalactionsofdrugsonthebody.Includeaction,mechanisms,indications,adversereactions,contraindicationsofthedrug.a.Pharmacodynamics

b.PharmacokineticsTorevealtheprinciplesofdynamicchangesofdruginthebody.Mainlydealingwiththechangeofdrugconcentrationinthedynamicsystemofabsorption,distribution,metabolismandexcretion(ADME).Whatisthedrugdoingtothebody.Whatisthebodydoingtothedrug.10Pharmacokinetics/PharmacodynamicsPHARMACOL.

EFFECTDoseofdrugadministeredDISTRIBUTIONABSORBANCECLEARANCEDoseatsiteofactionDruginsystemiccirculationDrugmetabolisedorexcretedDrugintissues11TheDutiesofPharmacologya.Toexplaintheactionanditsmechanismsofthedrug,toprovidethetheoreticalbasisforclinic,enhancingthedrugefficacyandreducingadversedrugreaction.b.Todevelopnewdrugandnewindicationsofdrug.c.Toexplorethepathwayofphysio-,biochemi-andpathologyofthecells.12RolesofPharmacologyKeysubjectofbasicmedicalsciences.Partofpharmacy.Bridges

subject:Exactlyimportantforaphysicianandclinicalpharmacisttotreatpatientsbydrugs.BasicMed.ClinicMed.PharmacyMedicinebridges132.HistoryandDevelopment

ofPharmacology(1)MateriaMedicainChina:longhistoryTheearliestwrittenrecordsfromChinaandfromEgyptlistremediesofmanytypes,includingafewstillrecognizedtodayasusefuldrugs.PenTsao（本草）

byShennong,100B.C.,365drugs;PenTsaoGangMu（本草綱目）byLiShi-zhen(1596),52vols,1852drugs.14(2)Pharmacology

intheWorldAdvancesinchemistry,biochemistryandthefurtherdevelopmentofphysiologyinthe18th,19th,andearly20thcenturieslaidthefoundationneededforunderstandinghowdrugsworkattheorganandtissuelevels.Researchersbegantodevelopthemethodsofexperimentalanimalphysiologyandpharmacology.15(2)Pharmacology

intheWorldGermanychemistF.W.Serturner(1783-1841)

--morphine

(嗎啡,1804)-analgesia--strychnine(1819)-actiononspinalcord,--caffeine(1819)-actiononCNS--quinine(1820),atropine(1831)P.Ehrlich(German,1906):

新胂凡納明,606-治療錐形病和梅毒

Sulfonamides(1935)-anti-infection

Fleming(England,1928)-penicillin16(2)Pharmacology

intheWorldR.Bochheim(Germany,1820-1879)–ExperimentalPharmacologyFirstpharmacol.lab,firstpharmacol.textbook,firstpharmacol.,ProfessorintheWorld.OswaldSchmiedeberg

(1838-1921)-OrganicPharmacologyP.Ehrlich,J.N.Langley(1852-1925):Receptortheory.17

Penicillin的發(fā)現(xiàn)(Fleming)Chance:1928，英國(guó)細(xì)菌學(xué)家弗萊明研究葡萄球菌,他發(fā)現(xiàn)培養(yǎng)細(xì)菌用的瓊脂上附了一層青霉菌。Surprisething，青霉菌周圍，葡萄球菌不見了。Attractivething,moreexperiments,培養(yǎng)青霉菌，證明青霉菌產(chǎn)生的物質(zhì)可以在幾小時(shí)內(nèi)將葡萄球菌全部殺死。Penicillin，葡萄球菌的克星。后經(jīng)生物化學(xué)家錢恩和病理學(xué)家弗洛里研發(fā)成藥。18

Fleming(弗萊明)Florey

(弗洛里)1945

NobelprizeinmedicineandphysiologyChain

(錢恩)1942年美國(guó)批量生產(chǎn)，用于挽救戰(zhàn)爭(zhēng)中大量傷病員。推進(jìn)了化學(xué)治療的發(fā)展。19

Wonderful—Aspirin20Aspirin1853年，熱拉爾（Gerhardt）用水楊酸與醋酐合成了乙酰水楊酸，但沒引起人們的重視；1898年，德國(guó)化學(xué)家霍夫曼（Hoffmann）重新合成，并為他父親治療風(fēng)濕性關(guān)節(jié)炎，取得巨大成功；1899年，由德萊塞（Dreser）介紹到臨床，取名為阿司匹林（Aspirin）。

21

Aspirin1999年3月6日德國(guó)拜爾（Bayer）公司在全世界范圍內(nèi)慶祝阿司匹林的百歲生日。100多年全世界的人們大約服用了數(shù)十億片阿司匹林，主要用于解熱、鎮(zhèn)痛、抗炎抗風(fēng)濕，后來又在防治心腦血管疾病方面大顯身手。22

PharmacologyinRecentYears

CalciumchannelblockersAngiotensinIconvertingenzymeinhibitorsStatinsATreceptorantagonistsDrugtargetsandActionMechanism-receptorThemolecularmechanismsofactionofmanydrugshavenowbeenidentified,andnumerousreceptorshavebeenisolatedstructurallycharacterized,andcloned.Thetransmembranesignalingorsignaltransductionhavebeenfound.eg.Gprotein,cAMP,PKA,etc.23

PharmacologyinChina

陳克恢(KKChen):麻黃堿ephedrine(1923)“TheFatherofAmericanPharmacology”(TIMES,1988)“TheFatherofChinesePharmacology”張昌紹，鄒岡：Analgesicsiteofmorphine(1963).金國(guó)章：羅通定，rotundine秦伯益：二氫埃托啡，dihydroetorphine青蒿素(artemisinin，1970)24TheMainBranchesofPharmacology臨床藥理學(xué)：Clinicalpharmacology生化藥理學(xué)：Biochemicalpharmacology分子藥理學(xué)：Molecularpharmacology藥物毒理學(xué)：DrugToxicology免疫藥理學(xué)：Immunopharmacology心血管藥理學(xué)：Cardiovascularpharmacology神經(jīng)藥理學(xué)：Neuropharmacology遺傳藥理學(xué)：Pharmacogenetics化學(xué)治療學(xué)：Chemotherapy25Dr.AJLehman,Chairman,DepartmentofPharmacology,FDA,USA“Youtoocanlearnpharmacology,inonlythreelessons:eachofthemlastingtenyears(學(xué)習(xí)藥理學(xué)也許僅需3節(jié)課，但每節(jié)課卻需要10年時(shí)間）”。3.MethodologyofLearningPharmacology263.MethodologyofLearningPharmacologyGraspthedrugclassificationaccordingtopharmacologicalactionFocusonhighlighteddrugsonthebasisofgeneralcharacterComparativelearning-thesameordifferentkindsofdrugsExperimentsReferences

BasicPrinciple:basicconcepts,basictheory

Systems:

PBL(Problembasedlearning)27ExamWewillhavequizsduringlecturesandfinalexamintheendofpharmacology.Thetypeofexamismainlychoicequestionsandsomewhatthepharmacologicaltermsoranswerquestions.ThelanguageoftestpaperisEnglish.284.PharmacologyinNewDrug

ResearchandDevelopmentNewdrugs(新藥):DrugswithoutmarketinginChinaandinworlddefinedasnewdrugbyChinaFoodandDrugAdministration(CFDA,未上市銷售的藥物)29ClinicalMarketingPreclinical-XStagesofDrugDevelopment30TheStepsforDrugResearch

andDevelopment(R&D)PreclinicalResearch:Pharmaceuticalstudies(藥學(xué)研究)

Physicalandchemicalproperties:Structure,technology,standard,quality,stabilityandpreparationstudies.Pharmacologicalstudies(animalexp.)

PharmacodynamicsstudiesGeneralPharmacologicalstudies:CNS、CVS、RSPharmacokineticsstudies:ADMEToxicologicalstudies:acute,chronic,specifictoxicity

31ApprovedClinicalPharmacology(human)PhaseⅠ:normal20-30subjectsPhaseⅡ:morethan100patientsPhaseⅢ:morethan300patientsmultiple-centertrial.ApprovedtomanufacturebyCFDAPhaseⅣ(postmarketingsurveillance)32AttritionRateSynthesis1000030Toxicology250AnimalExperimentsDecisionDecisionClinicalTrials5Decision3-6Y6-7Y0.5-2Y33TheOrganizationsandRegulationfor

NewDrugResearchandDevelopmentFoodandDrugAdministration(FDA,USA)ChinaFoodDrugAdministration(CFDA,China)TheCenterforNewDrugEvaluation.GLP(goodlaboratorypractice),GCP(G.clinicalP.),GMP(GmanufactureP.)34Appendices

處方藥（prescription-onlymedicines,ethicaldrugs,legenddrugs）非處方