1. Complexity of Antimicrobial Therapy (Antimicrobic Drug =antibiotic or synthetic drug) www.freelivedoctor.com Drug Delivery Problems Oral (destruction/poor uptake), Intravenous or Intramuscular (inconvenient), Topical , Poor Tissue Uptake , Injection into Body Cavity Wrong Drug Wrong Spectrum of Activity (informed best guess), Few Targets on Pathogen (fungi, protozoa, viruses) Drug Retention Problems Elimination from Host , Inactivation by Host Side Effects Toxicity to Host , Allergic Reaction , Normal Flora Disruption (superinfection) Antimicrobial Administration Selective Toxcity & Successful Delivery
2. Complexity of Antimicrobial Therapy www.freelivedoctor.com Toxins Exotoxins , Endotoxins (in Gram-negative septicemia antibiotic treatment can make situation even worse) Development of Resistance Evasion , Mutation-Mediated , Acquired (R plasmids) Prevention of Growth Bactericidal , Bacteriostatic , Host Defenses (elimination of pathogen from body) Prevent Resistance by Using… Only as Necessary , At sufficiently high doses for sufficiently long periods , In Combination Selective Toxcity & Successful Delivery
8. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosmal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
17. Various Antibiotics www.freelivedoctor.com Antibiotic Mode Spectrum of Activity Side Effects Ampicillin C Gram+, some neg. (broad) Allergic (diarrhea, anemia) Bacitracin C Gram+ (narrow) If injected: renal injury Clindamycin S Gram+ anaerobes (narrow) Diarrhea Erythromycin S Gram+ mycoplasma (narrow) Gastrointestinal upset, hepatic injury Isoniazod C Mycobacteria (narrow) Allergic, gastrointestinal upset, hepatic injury Penicillin C Gram+ (narrow) Allergic (nausea, anemia) Rifampin S Gram+ & mycobacteria (broad) Allergic, nausea, hepatic injury Streptomycin C Gram+, Gram-, & mycobacteria (broad) Allergic, nausea, renal injury, loss of hearing Sulfonamides S Gram+, Gram- (broad) Allergic (hepatic and renal injury, anemia) Tetracyclines S Gram+, Gram-, rickettsia, chlamydia Teeth discoloration, gastrointestinal upset (hepatic and renal injury)
18. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
19. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Cephalosporins Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
20. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
21. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
22. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
23. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
24. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Chloramphenicol Interferes with protein synthesis by binding to the bacterial ribosome Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
25. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Erytrhomycin Reversibly binds to ribosome, interfering with protein synthesis Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
26. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
28. Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it
