哈尔滨医科大学药理学1

药理学总论-绪言PharmacologyAVeryBasicIntroWhatisadrug?anychemicalagentwhich affectsanybiologicalprocess

SourcesofDrugs

AnimalsPlantsMineralsSyntheticMicrobesGeneticengineeringdrugs基因工程药物过程示意图①从细胞中分离出DNA①②③④⑤⑥②限制酶截取DNA片断③分离大肠杆菌中的质粒④DNA重组⑤用重组质粒转化大肠杆菌⑥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?

thestudyofhowdrugs effectbiologicalsystemsWhatisPharmacology?PharmacologyPharmacokineticsPharmacodynamics

WhatthebodydoestodrugWhatthedrugdoestobodyPharmacotherapeuticsPharmacocognosy

ThestudyoftheuseofdrugsIdentifyingcrudematerialsasdrugsToxicologyPharmacokineticsWhatthebodydoestothedrug-Absorption-Distribution-Metabolism(Biotransformation)-Excretion

Half-life(t1/2)-thetimerequiredfortheplasmaconcentrationofadrugtobereducedby50%DRUGCLASSIFICATION

Basedonthechemicalstructure

-Basedonthemaineffect(e.g.analgesics).-Basedonthetherapeuticuse(e.g.antipsychotic安定药).Basedonmechanismofaction(e.g.serotoninagonist).

FromChemisttoFirstInMan…approximately7–10yearsHowaDrugbecomesadrug…H.HaarmannUniversityofMaryland,2002EvaluatingDrugsinHumansTheFoodandDru