药理学总论英文(睢大员).ppt

Pharmacology DepartmentofPharmacologySchoolofPharmacyJilinUniversitySUIDa yuan睢大筼 WhatisPharmacology Chapter1Introduction basicmedicine Pharmacology pharmacy medicine clinicmedicine drugbroadlydefinedasanychemicalthataffectlivingprocesses usefulinprevention diagnosis treatmentofdiseases Chapter1Introduction Whatisadrug SourcesofDrugs Animals Plants Minerals Synthetics Microbes Geneticengineeringdrugs 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 drug TaskofPharmacology medicine pharamacodynamics pharmacokinetics body DevelopmentofPharmacology 上古时代公元前1世纪明代 公元1596年 近代药理学的发展迄今 Pharmacologicalresearchofnewdrugs pharmacodynamicsgeneralpharmacologypharmacokineticstoxicitology 1 preclinicaltest safetypharmacology Pharmacologicalresearchofnewdrugs period 20 30case period 200 300case period 400case period clinicaltrial 2000case 2 clinicalpharmacologicaltrial Section1Basicactionofdrugs Chapter2Pharmacodynamics stimulatorsorexcitants inhibitorsordepressants stimulationorexcitationdepressionorinhibition drugactiondrugeffect localactiongeneralaction Chapter2Pharmacodynamics therapeuticeffectadversdrugreaction selectivitydualism Chapter2Pharmacodynamics Therapeuticeffect etiologicaltreatmentsymptomatictreatment Chapter2Pharmacodynamics Adversdrugreaction sideaction econdaryreaction toxicreaction acutetoxcity chronictoxcity carcinogenesisteratogenesismutagenesis allergicreaction residualeffect withdrawalreaction Section2Receptivetheory Chapter2Pharmacodynamics Ligand L Effect E Receptor R Chapter2Pharmacodynamics receptortype channel linkdreceptorsG proteincoupledreceptorstyrosinekinase linkedreceptorsregulategenetranscriptionreceptors Ligand gatedionchannelreceptors Tyrosine proteinkinasereceptor Intracellularreceptors Chapter2Pharmacodynamics receptorregulation downregulationupregulationhomospecificregulationheterospecificregulation Chapter2Pharmacodynamics L R intrinsicactivity affinity E Chapter2Pharmacodynamics receptoragonist fullagonistpartialagonist receptorantagonist fullantagonistpartialantagonist competitiveantagonist non competitiveantagonist non competitiveantagonist drugactionandsignaitransduction Chapter2Pharmacodynamics gradedresponse quantalresponse Dose responserelationship Chapter2Pharmacodynamics minimumeffectivedose thresholddose maximumeffect Emax maximaldose Max D medianeffectivedose ED50 minimumtoxicdose Tmin medianlethaldose LD50 Dose responserelationship efficacy potency Dose responserelationship Emax ED50 efficacy potency 100 50 thresholddose Max D Tmin DoseResponseCurve Emax Emax Chapter2Pharmacodynamics LD50therapeuticindex TI ED50LD5safetyindex SI ED95 LD1 ED99 safetymargin SM 100 ED99 safetyevaluationofdrugs Chapter3Pharmacokinetics absorptiondistributionmetabolism biotransformation excretion Section1physiologicaldispositionofdrugs PharmacokineticPhase elimination Absorptiondistributionexcretion drugtransportthroughmembranes metabolism biotransformation Cellmembrane1 GIepithelialcells2 vascularendothelium3 bloodbrainbarrier BBB 4 subcellularmembranes 一 Drugtransportacrossmembranes 1 2 3 4 GIepithelialcells Vascularendothelium Bloodbrainbarrier BBB Subcellularmembranes A simplediffusion 1 Passivetransport B facilitateddiffusion C aqueousdiffusion acrossmembraneoflipid acrossaqueouschannel carriertransport outside inside 1 Passivetransport simplediffusion R D A C1 C2 X R diffusionrateD diffusionconstantA areaofmembrane C1 C2 concentrationgradientofdrugsX thicknessofmembrane ForaweakacidkaHAH A H A ka HA ka dissociationconstantpH logconcentration H logKaispKa Foraweakacid A pKa pH log HA A pH pKa log HA 10pH pKa A HA Foraweakbaseka H B BH H BKa BH BH pKa pH log B 10pka pH BH B Foraweakacid unionized pKa pH log ionized 10PH pka ionized unionized Foraweakbase ionized pKa pH log unionized 10pka pH ionized unionized If A HA or B BH pKa pH asubstanceishalfionizedandhalfnonionizedMustbecarefulyoumustknowpKa A pH pKa log HA BH orpKa pH log B 2 activetransport Examle Na K ATPase 3 cytosis pinocytosis exocytosis 1 Absorption themovementofadrugfromitssiteofadministrationintothebloodstream 二 drugprocessinbody Bloodstream drug drug 1 First passeffect influencingfactor thefirstpasseffectcanbeavoidedby sublingualrectuminhalationimsc GIhepaticportalveinlivervenacava 2 BioavailabilityfractionofanadministereddrugthatreachesthesystemiccirculationforIV Bioavailability 1 0 Minimumeffectiveconcentration 2 Distribution Bloodstream drug drugenterstheextracellularfluidsandtissuesofthebody drug cell 1 bindingofdrugbyplasmaproteins influencingfactor 2 bloodstreamoforgan 3 affinityoftissue 4 bloodbrainbarrier 5 placentalbarrier ApparentVolumeofDistribution Vd Vdishypotheticalvolume Vd A C 3 Metabolism twophases oxidationsreductionshydrolyses thefirstphase conjugations thesecondphase Hepaticmicrosomalenzymes enzymeinhibitor enzymeinducer mixedfunctionoxidases 4 Excretion excretionofkidneys excretionofbile excretionofmammarygland Hepatoenteralcirculation liver bile gallbladder duodenum excrete 4 Excretion 消除 transportandtransformationofdrugs Section2Basicconceptofpharmacokinetics A Time concentrationcurve thresholddose Cmax Tpeak TCmin B HalfLife t1 2 firstorderkineticst1 2 0 693 K zeroorderkineticst1 2 0 5C K C Compartmentmodel absoptioneliminationDrug one compartmentmodel two compartmentmodel drug centralcompartment peripheralcompartment absoption elimination D Clearance CL CL Vd Kor0 693 Vd t1 2 E Steadystateconcentration Css 三种不同给药方案对稳态浓度的影响A 缩短给药时间B 增加给药剂量C 负荷量给药 F Drugeliminationrate dc dt KCnC concentrationofthedrugK eliminationrateconstant n 1firstorderkinetics dc dt KC1 n 0zeroorderkinetics dc dt KC0 Vmax Firstorderkinetics constantfractionofdrugiseliminatedperunittime Zeroorderkinetics samequantityofdrugiseliminatedperunittime RoutesofDrugAdministrationcommonabbreviations po peros oraliv intravenous intotheveinim intramuscular intothemusclesc subcutaneous betweentheskinandmuscleip intraperitoneal withintheperitonealcavityicv intracerebroventricular directlyintotheventricleofthebrain Chapter4Factorsaffectingeffectofdrugs ageandsexmentalandpathologicfactorsindividualvariationandgeneticsspeciesvariation Section1Factorsaboutorganismaspect ageandsex age infants agedpeople ageandsex sex male female mentalfactor spiritandbodydisease bodyandspiritdisease placeboactions mentalandpathologicfactors mentalandpathologicfactors pathologicfactor dystrophy renalinadequacy hepaticinadequacy individualvariationandgeneticfactors individualvariation hypersensitivereaction tolerance hypersensitivity individualvariationandgeneticfactors geneticfactors haemolyticusanemia maliganemia methemoglobinemia speciesvariation animal race Chapter4Factorsaffectingeffectofdrugs doseanddosageformrouteandtimeofadministrat