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INTRODUCTION TO CHEMOTHERAPEUTIC DRUGS 1. Brief History of Chemotherapeutic Drugs 2. Several Terms related to Chemotherapy Chemotherapy/Chemotherapeutic index(CI)/Antibacterial drugs/Antibiotics/Antibacterial spectrum/Bacteriostatic drugs/Bactericidal drugs/Minimum inhibitory concentration(MIC)/Minimum bactericidal concentration(MBC) /PAE 3.Mechanism of action of Antimicrobial Agents (1)Inhibition of cell wall synthesis : β-lactam/ vancomycin (2)Interfering with cell membrane permeability: Polymixins/Amphotericin B (3)Inhibition of protein synthesis: Aminoglycosides/Tetracyclines/Chloramphenicol/Macrolides/Clindamycin (4)Inhibition of nucleic acid synthesis: Rifampicin/Quinolones/Sulfonamides/ TMP 4. Bacterial resistance to antimicrobial agents (1)Reasons : Antibiotics abuse (2)Classification: Intrinsic resistance /Acquired resistance (3)Mechanism of microbial resistance ①Production of enzyme that destroy the drugs: β-lactamase /Adenylase, phosphorylase, acetyltransferase ②Alteration of target for the drugs ③Alteration of membrane permeability ④Active efflux system ⑤Alteration of the metabolism route (4)Brief introduction: ESBLs: extended spectrum β-Lactamases/ Pseudomonus aeruginosa MRSA: Methicillin resistant Staphylococcus aureus/ VRE: Vancomycin resistant Enterococci (5)Rational use of antimicrobial agents ①Basic principles: Diagnosis \Rational use: Newborn/Pregnancy/Elderly/Immune function ②Misuse: Virus infection/Unknown fever/Topical use ③Antimicrobial prophylaxis Surgical prophylaxis: Infectious endocarditis/Trauma, burn/operation Nonsurgical prophylaxis: Rheumatic fever/Epidemic meningitis/Malaria, Tuberculosis ④Antimicrobial agents combination Synergism & antagonism Drug categories: 1.β-Lactam antibiotics/2.Aminoglycosides 3.Tetracyclines, macrolide ,chloramphenicol/ 4.Sulfonamides Rational use of antimicrobial agents 1+2: Synergism/ 1+3:antagonism/ 2+3:synergism or plus/ 3+4: plus ⑤Rationale for combination antimicrobial therapy To Provide broad-spectrum empirical therapy in seriously ill patients/ Serious infection that can not be controlled by one drug/ To decrease the emergence of resistant strains / To decrease dose-related toxicis. 1