药理学精品教学汕头大学introductiontoantimicrobialagents.ppt

Definition:Use of drugs to combat infectious diseases and cancer.Antimicrobial drug(抗微生物药)Antiparasitic drug(抗寄生虫药)Anticancer drug(抗癌药)1.Chemotherapy,化学治疗化学治疗Antimicrobial drugAntimicrobial drugs either kill microbes (microbicidal)or prevent the growth of microbes(microbistatic).Antibacterial(抗菌药）Antiviral（抗病毒药）Antifungal（抗真菌药）Antimicrobial ChemotherapyDifferential toxicity:based on the concept that the drug is more toxic to the infecting organism than to the hostMajority of antibiotics are based on naturally occurring compounds(antibiotics)or may be semi-synthetic or syntheticDefinitions（抗菌谱）Definitions-minimum concentration of antibiotic required to inhibit the growth of the test organism-minimum concentration of antibiotic required to kill the test organismDefinitionsBacteriostatic（抑菌药）Bactericidal（杀菌药）What is the ideal antibioticHave the appropriate spectrum of activity for the clinical settingHave no toxicity to the host,be well toleratedLow propensity for development of resistanceNot induce hypersensitivies in the hostWhat is the ideal antibioticHave rapid and extensive tissue distributionHave a relatively long half-lifeBe free of interactions with other drugsBe convenient for administrationBe relatively inexpensivepathogenic microorganismantibacterial action resistanceDisease Resistance pathogenicity adverse reaction intracorporal process bodyThe glycan backbone Peptidoglycan cross-bridgesTetrapeptide side chainTargets of antimicrobial drugs and aAmphotericin B Drugs that disrupt cell membrane functionInhibition of protein synthesisGenerally work at different stages of prokaryotic mRNA translation into proteins,like initiation,elongation(including aminoacyl tRNA entry,proofreading,peptidyl transfer and ribosomal translocation)and termination.)The antibiotic only affects 70S ribosomes in the bacteria and does nothing for the 80S ribosomes in human.Inhibition of protein synthesis Macrolides Lincomycin Chloromycetin TetracyclinesAminoglycosidesbind to 50sbind to 30sDNA replication Inhibitors of nucleic acid synthesisAntibiotics that mimic the structure of the specific substrate that the normal substrate is replaced and dont have contact with the enzyme which acts on a substrate to produce a certain metabolically important metabolite inside the cell.Action of sulfanilamide Antimicrobial resistance:the inability to kill or inhibit the organism with clinically achievable drug concentrations Antimicrobial resistanceResistance may be innate(naturally resistant)Resistance may be acquired -mutation -acquisition of foreign DNAInactivation/destruction of antibiotic:production of Altered binding site:PBPAltered permeability:OprDEfflux (pumps)mechanisms Acquired resistanceMutation Transduction(转导）:phageTransformation（转化）Conjugation:plasmidResistance gene transmissionResistanceMDR:Multi-drug resistance（多重耐药）MRSA(甲氧西林耐药金黄色葡萄球菌）;MRCNS（凝固酶阴性，耐甲氧西林表皮葡萄球菌和溶血葡萄球菌）PRSP：青霉素耐药肺炎链球菌VRE：万古霉素耐药肠球菌Resistance-lactmaseOverprecribition/irrational use of antibioticsSuperinfection Adverse drug reactionResistanceDifficult for diagnosisWasting moneyAntimicrobial drugsInfection caused by bacteria,richettsia,leptospira,mycoplasma,ray fungiCan not used in virus infection without bacterial infection;fever with unknown cause;local infection without general symptom;Prophylaxis and combined use of antibioticsSelection of antimicrobial agents A.Empiric therapy B.Identification and sensitivity of the organism C.Site of infection D.Status of the patient E.Safety of the agent G.Cost of therapyCost of the therapy Cost=efficiencyOverprecribition:Prevention of rheumatic fever（风湿热）Epidemic cerebrospinal meningitis(流行性脑脊膜炎）Prevention of tuberculosisOphthalmia neonatorum（新生儿眼炎)Prevention of ague(疟疾）Indication of combined medication Serious infection with unknown cause Mixed infection No satisfactory effect with one antibioticsLong term use of antibiotics,prevent the emergence of resistance to one antibioticsReduce toxic reactionImmunodeciency patientEffect of combined medicationObjective：increase effect;prevent resistance;reduce toxicityEffect：synergistic;additive;unrelated;antagonistic