药理学总论-绪言【精品-ppt】

药理学总论 绪言PharmacologyAVeryBasicIntro Whatisadrug anychemicalagentwhichaffectsanybiologicalprocess SourcesofDrugs AnimalsPlantsMineralsSyntheticMicrobesGeneticengineeringdrugs 基因工程药物过程示意图 从细胞中分离出DNA 限制酶截取DNA片断 分离大肠杆菌中的质粒 DNA重组 用重组质粒转化大肠杆菌 培养大肠杆菌克隆大量基因 AgoalofGenomicsistofindandexpressgenesthatcodeforunknownpeptideswithsignificantbiologicalproperties likereceptorsorenzymes InareversePharmacologyapproachthispeptide e g areceptor isthenusedto fish foranaturalligand Withreceptorandligandinhandthebiologicalroleofthereceptorneedstobedetermined Finally screeningforsyntheticligandsaswellasleadoptimizationcanleadtonewdrugcandidates Incontrast theclassicalapproachtodrugdiscoverystartswiththeidentificationofaligandthathasbiologicalactivitythatinturnisusedto fish forthecorrespondingreceptor OneexampleforaGenomicsstrategyaimsatidentifyingdrugtargetsbasedonmolecularhomologywithinGene families Oneofthemostimportantfamiliesofdrug targetsforthepharmaceuticalindustryisthefamilyofG proteincoupledreceptors GPCRs Ofthetop200bestsellingprescriptiondrugs morethan20 interactwithGPCRs providingworldwidesalesofover 20billion ThecharacteristicmotifoftheGPCRfamilyisthesevendistincthydrophobicregions eachof20to30aminoacidsthatformthetransmembranedomainoftheseintegralmembraneproteins Thiskeyamino acidsequencemotifcanbefoundwithinalltypesofGPCRsandcanbeusedtoidentifyDNA sequencesthatcodeforGPCRs Whatispharmacology thestudyofhowdrugseffectbiologicalsystems WhatisPharmacology Pharmacology PharmacokineticsPharmacodynamicsWhatthebodydoestodrugWhatthedrugdoestobody PharmacotherapeuticsPharmacocognosyThestudyoftheuseofdrugsIdentifyingcrudematerialsasdrugs Toxicology PharmacokineticsWhatthebodydoestothedrug Absorption Distribution Metabolism Biotransformation Excretion Half life t1 2 thetimerequiredfortheplasmaconcentrationofadrugtobereducedby50 DRUGCLASSIFICATIONBasedonthechemicalstructure Basedonthemaineffect e g analgesics Basedonthetherapeuticuse e g antipsychotic安定药 Basedonmechanismofaction e g serotoninagonist FromChemisttoFirstInMan approximately7 10yearsHowaDrugbecomesadrug H HaarmannUniversityofMaryland 2002 Basic ClinicalEvaluationofNewDrugsDrugdiscovery DrugscreeningChemistryInVitroStudiesFunctionincells tissues andatreceptors2 Preclinicalsafety toxicitytestingInVivo AnimalstudiesPharmacologyandBehavioralPharmacologyPotencyandEfficacy ED50ToleranceandTachyphylaxis 快速耐受 Toxicity AcuteandChronicLD50Teratogenicity birthdefectsCarcinogenicity cancerous3 Evaluationofdruginhumans EvaluatingDrugsinHumans TheFoodandDrugAdministration FDA PhasesofaClinicalTrialsPhaseIPhaseIIPhaseIIIPhaseIV EvaluatingDrugsinHumans PhaseI HealthyadultvolunteersEvaluationofsafety Pharmacokinetics PK sideeffects PhaseII PatientsEvaluationofefficacy safety PK andsideeffectsDouble blindplacebocontrolledPhaseIII SpecificpatientsubpopulationsDetermineefficacyforspecificindicationsLargesampleofspecificpatients 1 000 Randomizeddouble blindplacebocontrolledPhaseIV PostFDAApprovalDetermineefficacyforspecificindicationDeterminedrugutilizationpatternsandadditionalefficacyMonitorrare severesideeffects toxicity DrugNomenclature Chemicalname 化学名 Genericname 非专利名 Tradename 商品名 ChemicalName 2 4 isobutylphenyl propionicacidGenericName ibuprofen 布洛芬 TradeN