药理学总论英文(睢大员)

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1、 SUI Da-yuan 睢大筼睢大筼 What is Pharmacology? Chapter 1 Introduction basic medicine Pharmacologypharmacy medicine clinic medicine - Chapter 1 IntroductionWhat is a drug?Sources of DrugsAnimalsPlants MineralsSyntheticsMicrobesGenetic engineering drugs基因工程药物过程示意图基因工程药物过程示意图 drugTask of Pharmacologymedicin

2、epharamacodynamicspharmacokineticsbodyDevelopment of Pharmacology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Pharmacological research of new drugs pharmacodynamics general pharmacology pharmacokinetics toxicitology 1、 preclinical testsafety pharmacologyPharmacological research of new drugs period : 2030 case per

3、iod : 200300 case period : 400 case period : clinical trial2000 case2、 clinical pharmacological trial Section 1 Basic action of drugsChapter 2 stimulators or excitantsinhibitors or depressantsstimulation or excitation depression or inhibitiondrug action drug effect local action general action Chapte

4、r 2 therapeutic effect advers drug reactionselectivity dualismChapter 2 Therapeutic effect etiological treatment symptomatic treatment Chapter 2 Advers drug reaction side action econdary reactiontoxic reactionacute toxcitychronic toxcitycarcinogenesisteratogenesismutagenesisallergic reactionresidual

5、 effect withdrawal reaction Section 2 Receptive theoryChapter 2 Ligand (L)Effect (E)Receptor (R)Chapter 2 receptor typechannel-linkd receptorsG-protein coupled receptorstyrosine kinase-linked receptorsregulate gene transcription receptors激动药结合区域激动药结合区域膜外膜外膜内膜内激动药结合区域激动药结合区域 Ligand-gated ion channel

6、receptorsG蛋白偶联蛋白偶联CN激动药结合区域激动药结合区域膜外膜外膜内膜内 G-protein coupled recptors激动药结合区域激动药结合区域膜外膜外膜内膜内催化结构区域催化结构区域 Tyrosine-protein kinase receptor激动药结合区域激动药结合区域膜外膜外膜内膜内DNA结合区域结合区域转录激活区域转录激活区域载体载体 + 药物药物载体载体-药物复合物药物复合物载体载体 + 药物药物载体载体 Intracellular receptorsChapter 2 receptorregulationdown regulationup regulati

7、onhomospecific regulationheterospecific regulationChapter 2 LRintrinsic activityaffinityEChapter 2 receptor agonistfull agonistpartial agonistreceptor antagonist full antagonist partial antagonistcompetitive antagonistnon-competitive antagonistnon-competitive antagonistdrug action and signai transdu

8、ctionChapter 2 graded responsequantal response Dose-response relationshipChapter 2 minimum effective dose (threshold dose)maximum effect (Emax)maximal dose (Max-D)median effective dose (ED50) minimum toxic dose (Tmin)median lethal dose (LD50)Dose-response relationshipefficacypotencyDose response cur

9、ve.Dose-response relationship EmaxED50efficacypotency100%50%threshold doseMax-DTminDose Response CurveEmaxEmaxChapter 2 LD50therapeutic index (TI) = ED50 LD5safety index (SI) = ED95 (LD1 - ED99)safety margin (SM) = 100% ED99safety evaluation of drugsChapter 3 Pharmacokinetics absorption distribution

10、 metabolism (biotransformation) excretionSection 1 physiological disposition of drugsPharmacokinetic PhaseeliminationAbsorptiondistribution excretiondrug transport through membranesmetabolismbiotransformation Cell membrane 1) GI epithelial cells 2) vascular endothelium 3) blood brain barrier (BBB) 4

11、) subcellular membranes 一、一、Drug transport across membranes1234GI epithelial cellsVascular endotheliumBlood brain barrier(BBB)Subcellular membranesA. simple diffusion1. Passive transportB. facilitated diffusionC. aqueous diffusionacross membraneof lipidacross a q u e o u s channelc a r r i e r trans

12、portoutsideinside1. Passive transport simple diffusion R = DA (C1 - C2) / XR: diffusion rate D: diffusion constantA: area of membrane(C1-C2): concentration gradient of drugsX: thickness of membrane For a weak acid ka HA H+ + A- H+ A- ka = HA ka : dissociation constant pH = - log concentration H+ - l

13、og Ka is pKa For a weak acid A-pKa = pH -log HA A-pH - pKa = log HA10 pH - pKa = A- / HAFor a weak base ka H+B BH+ H+ + B Ka = BH+ BH+ pKa pH = log B10 pka pH = BH+ / B For a weak acid unionized pKa = pH + log ionized 10 PH-pka = ionized / unionizedFor a weak base ionized pKa = pH + log unionized 10

14、pka-pH= ionized / unionized If A-= HA or B=BH+ - pKa = pH - a substance is half ionized and half nonionized Must be careful you must know pKa A-pH - pKa = log HA BH+or pKa pH = log B 2. active transport Examle : Na+-K+ ATPase 3. cytosis pinocytosisexocytosis 1. Absorption the movement of a drug from

15、 its site of administration into the bloodstream二、二、drug process in bodyBloodstreamdrugdrug1) First-pass effectinfluencing factor the first pass effect can be avoided by sublingual rectum inhalation im sc GI hepatic portal vein liver vena cava 2) Bioavailability fraction of an administered drug that

16、 reaches the systemic circulation for IV, Bioavailability = 1.0 Fomulation AFomulation BFormulation CConcentration of drug in plsmaMinimum toxic concentrationMinimum toxic concentrationTimeMinimum effective concentration 2. DistributionBloodstreamdrugdrug enters the extracellular fluids and tissues

17、of the bodydrugcell 1) binding of drug by plasma proteinsinfluencing factor2) bloodstream of organ3) affinity of tissue4) blood brain barrier5) placental barrier Apparent Volume of Distribution (Vd)Vd is hypothetical volume Vd = A / C 3. Metabolism two phases oxidationsreductionshydrolyses the first

18、 phase conjugationsthe second phaseHepatic microsomal enzymesenzyme inhibitorenzyme inducermixed function oxidases 4. Excretion excretion of kidneysexcretion of bileexcretion of mammary gland Hepatoenteral circulation liver-bilegall bladder duodenumexcrete 4. Excretion 消除消除transport and transformati

19、on of drugs Section 2 Basic concept of pharmacokineticsMinimum toxic concentrationPeak timePeak concentrationBalance phaseMinimum effective concentrationElimination phaseLatent periodResidual periodTimeConcentration of drug in plsmaSafety rangeDurationAbsorption and distribution phaseA. Time-concent

20、ration curvethreshold dose CmaxTpeakTCmin B. Half Life (t1/2) first order kinetics t1/2 = 0.693/K zero order kinetics t1/2 = 0.5C/K C. Compartment model absoption eliminationDrug one-compartment model00.20.40.60.811.21.41.650101520Time(h)Log concentration (ug/ml)Atwo-compartment model drug central c

21、ompartment peripheralcompartmentabsoptionelimination00.20.40.60.811.21.450101520Tim e(h)Log concentration (ug/ml)B2530 D. Clearance (CL)CL = Vd . K or 0.693.Vd/t1/20210123456Steady stateconCss.maxCss.min7 E. Steady state concentration (Css) 血血药药浓浓度度100200300802460002468100200300时间（半衰期）时间（半衰期）1002003

22、0002460ABC8MTCMEC三种不同给药方案对稳态浓度的影响三种不同给药方案对稳态浓度的影响A. 缩短给药时间缩短给药时间 B. 增加给药剂量增加给药剂量 C. 负荷量给药负荷量给药F. Drug elimination rate dc/dt = -KCn C: concentration of the drug K: elimination rate constantn=1 first order kinetics -dc/dt = KC1n=0 zero order kinetics -dc/dt = KC0 = VmaxFirst order kinetics: constant

23、fraction of drug is eliminated per unit timeZero order kinetics : same quantity of drug is eliminated per unit timeRoutes of Drug Administrationcommon abbreviationspo = per os = oraliv = intravenous = into the veinim = intramuscular = into the musclesc = subcutaneous = between the skin and muscleip

24、= intraperitoneal = within the peritoneal cavityicv = intracerebroventricular =directly into the ventricle of the brainChapter 4 Factors affecting effect of drugs age and sex mental and pathologic factors individual variation and genetics species variationSection 1 Factors about organism aspect age

25、and sexage infants aged people age and sexsexmalefemalemental factor spirit and body diseasebody and spirit diseaseplacebo actions mental and pathologic factors mental and pathologic factorspathologic factordystrophyrenal inadequacyhepatic inadequacyindividual variation and genetic factorsindividual

26、 variationhypersensitive reactiontolerancehypersensitivityindividual variation and genetic factorsgenetic factors haemolyticus anemiamalig anemiamethemoglobinemiaspecies variationanimalrace Chapter 4 Factors affecting effect of drugs dose and dosage form route and time of administration medication r

27、epeatedly drug interactionSection 2 Factors about drug aspect dose and dosage formdosedosage form route and time of administrationroutetime medication repeatedlytoleranceresistancedrug dependencephysical dependencepsychic dependenceaddictionhabituationabstinence drug interactionpharmacokineticsabsor

28、ptiondistributionmetabolism excretion drug interactionpharmacodynamicssynergismadditive effectpotentiationsensitization drug interactionpharmacodynamicsantagonismpharmacological antagonismphysiological antagonismbiochemical antagonismchemical antagonismpharmacokinetics summary of general introductionpharmacodynamicsPharmacologydualismtherapeutic effectadvers reaction absorption distribution metabolism excretion ANY QUESTIONS？ THANK YOU！