Complexity of Antimicrobial Therapy (Antimicrobic Drug =antibiotic or synthetic drug) www.freelivedoctor.com Drug Delivery...
Complexity of Antimicrobial Therapy www.freelivedoctor.com Toxins Exotoxins , Endotoxins (in Gram-negative septicemia anti...
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Antibiotics Sources www.freelivedoctor.com
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Sites of Antibiotic Action www.freelivedoctor.com Site of Action Antibiotic Examples Cell wall (peptidoglycan) synthesis  ...
Antibiotic Modes of Action www.freelivedoctor.com
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Spectrum of Activity Narrow Spectrum Wide Spectrum www.freelivedoctor.com
Informed Best Guess www.freelivedoctor.com
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure  </li></ul...
Various Antibiotics www.freelivedoctor.com Antibiotic Mode Spectrum of Activity Side Effects Ampicillin C Gram+, some neg....
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
Blocking Ribosome Function www.freelivedoctor.com
Antibiotic Modes of Action www.freelivedoctor.com Drug Mode of Action Vancomycin Binds to D-Ala-D-Ala terminus; inhibits t...
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Complexty Of Antimicrobial Therepy

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Complexty Of Antimicrobial Therepy

  1. 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. 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
  3. 3. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  4. 4. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  5. 5. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  6. 6. Antibiotics Sources www.freelivedoctor.com
  7. 7. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  8. 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
  9. 9. Sites of Antibiotic Action www.freelivedoctor.com Site of Action Antibiotic Examples Cell wall (peptidoglycan) synthesis <ul><li>Glycopeptides </li></ul><ul><li>B-lactams </li></ul>Replication or transcription of genetic material <ul><li>Quinolones </li></ul><ul><li>Nitroimidazoles </li></ul><ul><li>Rifampicin </li></ul>Protein synthesis <ul><li>Aminoglycosides </li></ul><ul><li>Chloramphenicol </li></ul><ul><li>Macrolides </li></ul>Cell membrane functions (fungi) <ul><li>Polymixins </li></ul>Antimetabolites <ul><li>Diaminopyrimidines </li></ul>
  10. 10. Antibiotic Modes of Action www.freelivedoctor.com
  11. 11. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  12. 12. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  13. 13. Spectrum of Activity Narrow Spectrum Wide Spectrum www.freelivedoctor.com
  14. 14. Informed Best Guess www.freelivedoctor.com
  15. 15. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  16. 16. Distinguishing Antibiotics <ul><li>Antibiotics differ in terms of… </li></ul><ul><li>… their chemical structure </li></ul><ul><li>… the organism they are or were isolated from </li></ul><ul><li>… their site of action in bacterial cells </li></ul><ul><li>… bacteriostasis versus bacteriostatic </li></ul><ul><li>… the spectrum of bacteria they are active against </li></ul><ul><li>… the degree to which susceptible organisms are capable of evolving resistance </li></ul><ul><li>… toxicity to the host </li></ul>www.freelivedoctor.com
  17. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
  27. 27. Blocking Ribosome Function www.freelivedoctor.com
  28. 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

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