药理学总论英文睢大员

1、药理学总论英文睢大员 What is Pharmacology? Chapter 1 Introduction basic medicine Pharmacologypharmacy medicine clinic medicine - drug broadly defined as any chemical that affect living processes - useful in prevention, diagnosis, treatment of diseasesChapter 1 IntroductionWhat is a drug?Sources of DrugsAnimal

2、sPlants MineralsSyntheticsMicrobesGenetic engineering drugs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 drugTask of PharmacologymedicinepharamacodynamicspharmacokineticsbodyDevelopment 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 pharm

3、acodynamics general pharmacology pharmacokinetics toxicitology 1、 preclinical testsafety pharmacologyPharmacological research of new drugs period : 2030 case period : 200300 case period : 400 case period : clinical trial2000 case2、 clinical pharmacological trial Section 1 Basic action of drugsChapte

4、r 2 Pharmacodynamicsstimulators or excitantsinhibitors or depressantsstimulation or excitation depression or inhibitiondrug action drug effect local action general action Chapter 2 Pharmacodynamicstherapeutic effect advers drug reactionselectivity dualismChapter 2 Pharmacodynamics Therapeutic effect

5、 etiological treatment symptomatic treatment Chapter 2 PharmacodynamicsAdvers drug reaction side action econdary reactiontoxic reactionacute toxcitychronic toxcitycarcinogenesisteratogenesismutagenesisallergic reactionresidual effect withdrawal reaction Section 2 Receptive theoryChapter 2 Pharmacody

6、namicsLigand (L)Effect (E)Receptor (R)Chapter 2 Pharmacodynamicsreceptor typechannel-linkd receptorsG-protein coupled receptorstyrosine kinase-linked receptorsregulate gene transcription receptors激动药结合区域膜外膜内激动药结合区域 Ligand-gated ion channel receptorsG蛋白偶联CN激动药结合区域膜外膜内 G-protein coupled recptors激动药结合区

7、域膜外膜内催化结构区域 Tyrosine-protein kinase receptor激动药结合区域膜外膜内DNA结合区域转录激活区域载体 + 药物载体-药物复合物载体 + 药物载体 Intracellular receptorsChapter 2 Pharmacodynamicsreceptorregulationdown regulationup regulationhomospecific regulationheterospecific regulationChapter 2 PharmacodynamicsLRintrinsic activityaffinityEChapter 2

8、 Pharmacodynamicsreceptor agonistfull agonistpartial agonistreceptor antagonist full antagonist partial antagonistcompetitive antagonistnon-competitive antagonistnon-competitive antagonistdrug action and signai transductionChapter 2 Pharmacodynamicsgraded responsequantal response Dose-response relat

9、ionshipChapter 2 Pharmacodynamicsminimum 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 relationship EmaxED50efficacypotency100%50%threshold

10、doseMax-DTminDose Response CurveEmaxEmaxChapter 2 Pharmacodynamics LD50therapeutic index (TI) = ED50 LD5safety index (SI) = ED95 (LD1 - ED99)safety margin (SM) = 100% ED99safety evaluation of drugsChapter 3 Pharmacokinetics absorptiondistributionmetabolism (biotransformation) excretionSection 1 phys

11、iological disposition of drugsPharmacokinetic PhaseeliminationAbsorptiondistribution excretiondrug transport through membranesmetabolismbiotransformation Cell membrane 1) GI epithelial cells 2) vascular endothelium 3) blood brain barrier (BBB) 4) subcellular membranes 一、Drug transport across membran

12、es1234GI epithelial cellsVascular endotheliumBlood brain barrier(BBB)Subcellular membranesA. simple diffusion1. Passive transportB. facilitated diffusionC. aqueous diffusionacross membraneof lipidacross aqueous channelcarrier transportoutsideinside1. Passive transport simple diffusion R = DA (C1 - C

13、2) / 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+ - log Ka is pKa For a weak acid A-pKa = pH -log HA A-pH - pKa = log HA10

14、 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 10pka-pH= ionized / unionized If A-= HA or B=BH+ - pKa = pH - a substan

15、ce 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 its site of administration into the bloodstream二、drug process in bod

16、yBloodstreamdrugdrug1) 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 reaches the systemic circulation for IV, Minimum effective concentrati

17、on 2. DistributionBloodstreamdrugdrug enters the extracellular fluids and tissues 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 v

18、olume Vd = A / C 3. Metabolism two phases oxidationsreductionshydrolyses the first phase conjugationsthe second phaseHepatic microsomal enzymesenzyme inhibitorenzyme inducermixed function oxidases 4. Excretion excretion of kidneysexcretion of bileexcretion of mammary gland Hepatoenteral circulation

19、liver-bilegall bladder duodenumexcrete 4. Excretion 消除transport and transformation of drugs Section 2 Basic concept of pharmacokineticsA. Time-concentration curvethreshold dose CmaxTpeakTCmin B. Half Life (t1/2) first order kinetics t1/2 zero order kinetics t1/2 C. Compartment model absoption elimin

20、ationDrug one-compartment modeltwo-compartment model drug central compartment peripheralcompartmentabsoptionelimination D. Clearance (CL)CL = Vd . K or1/20210123456Steady stateconCss.maxCss.min7 E. Steady state concentration (Css) 血药浓度100200300802460002468100200300时间（半衰期）10020030002460ABC8MTCMEC三种不同

21、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. 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 fraction of drug is eliminated per unit timeZero order

22、 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 = intraperitoneal = within the peritoneal cavityicv =

23、intracerebroventricular =directly into the ventricle of the brainChapter 4 Factors affecting effect of drugs age and sexmental and pathologic factorsindividual variation and genetics species variationSection 1 Factors about organism aspect age and sexage infants aged people age and sexsexmalefemalem

24、ental factor spirit and body diseasebody and spirit diseaseplacebo actions mental and pathologic factors mental and pathologic factorspathologic factordystrophyrenal inadequacyhepatic inadequacyindividual variation and genetic factorsindividual variationhypersensitive reactiontolerancehypersensitivityindividual variation and genetic factorsgenetic factors haemolyticus anemiamalig anemiamethemoglobinemiaspecies variationanimalrace Chapter 4 Factors affecting effect of d