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L8 Antimicrobial agents - Coggle Diagram

- - - - High mortality if compromised immune system
        
        AIDS
        
        Chronic granulomatous disease
        
        NADPH oxidase deficiency
        
        Post-organ transplant
        
        Immune suppressant drugs
- - - - Only decrease growth rate
      - Works well alone in healthy immune systems
    - - Kill bacteria (via irreversible attachment)
      - Needed additionally if weak immunity
      - Interfere with cross-linking of cell wall
        
        Bacteria vulnerable to swelling/lysis
  - - - Affects bacterial cell wall formation
      - Nucleic acid formation
      - Protein synthesis inhibition at ribosomal level
      - Disrupts microbial cell membrane
- - - - Overly broad spectrum of agents
  - - - Gram +ve/-ve have different agent access
        
        +ve have only cell wall, no membrane
        
        Easier for agents to enter
        
        -ve have an outermost cell membrane
        
        Prevents agent entry
      - Mutations can change cell surface
    - - Tetracycline (antibiotic)
        
        Accumulated by sensitive bacteria but not by resistant ones
      - Aminoglycosides (antibiotic)
        
        Accumulated by bacteria if O2 present
        
        Resistant to anaerobic bacteria
        
        Drug doesn't work in ischemic regions
    - - Penicillin binding proteins present
        
        Drug accumulated by bacteria
      - PBP not present (removed by mutation in bacteria)
        
        Bacteria resistant to drug
    - - Penicillinase
        
        Penicillin
      - Acetyl transferase
        
        Chloramphenicol
      - Phosphorylase, acetylase
        
        Aminoglycosides
      - Newer agents, less inactivation (less enzymes)
- - - - Folic acid synthesis
        
        DNA synthesis
      - Competes; blocks folic acid synthesis
    - - No more growth possible
    - - Sulfonamide resistance
    - - Sulfonamide
      - Trimethoprim (inhibits dihydrofolate reductase)
  - - - But bacterial enzymes are much more sensitive to trimethoprim
      - Dihydrofolate --> Tetrahydrofolate
    - - Blocks folic acid synthesis
  - - - Herpes thym kinase is more sensitive to acyclovir
        
        Immediate conversion to acyclovir triphosphate
        
        Viral DNA polymerase inhibition
        
        Viral DNA more affinity for acyclovir triphosphate (like Stockholm syndrome)
  - - - No thymidine kinase
        
        CMV is resistant to acyclovir
    - - Conversion to ganciclovir triphosphate
        
        CMV DNA Polymerase inhibition
  - - - Phosphatidyl ethanolamine on outer bacterial membrane
        
        In non-bacterial cells, mostly in inner membrane surface
        
        Some interactions with host cell membranes (Relatively toxic)
        
        More selective to bacterial (-ve; membrane)
        
        Use topically (skin cream, mouthwash)
        
        Destabilize membrane
        
        Cell lysis
  - - - Bacterial membranes lack sterols (unaffected)
        
        Affect some mammlian cells
        
        Use topically
    - - Stable complex polyene-ergosterol
      - Membrane destabilization
        
        Cell lysis
  - - - Orally effective, low toxicity
    - - Leaky membrane
  - - - Transpeptidase catalyzes cross linking by binding to D-ala-D-ala
    - - Irreversible
      - Cross-linking prevented (improper cell wall)
        
        Cells susceptible to lysis
        
        Vancomycin, bacitracin also do this
    - - Inhibits transpeptidase
        
        Blocks cell wall formation
      - Activate enzymes that cause cell autolysis
      - Inhibit cell division
      - Mutations in PBP affect cell sensitivity to penicillin
        
        May prevent cell autolysis in bacteria
        
        Defective cell wall but survives
      - Penicillin access gram-ve PBP via porin channels (pores)
    - - Altering R group
        
        Affects antibacterial spectrum & resistance to degradation by penicillinase
    - - Rapid urinary excretion
        
        Frequent doses
        
        Give with inert organic acid (Probenecid) to decrease excretion
      - Forms salt (excreted)
  - - - Pre-surgery (prophylaxis) for immune-compromised patients
        
        Now resistant...
  - - - Only targets bacterial RNA polymerase
    - - Preserves sensitivity
  - - - Converted to nucleoside triphosphate
        
        Inhibit reverse transcriptase
        
        Blocks viral DNA synthesis
    - - For AIDS (toxic)
      - Lamivudin (hepatitis B)
  - - - Resistant
  - - - Bone marrow depression (Less RBC prod) side effect
        
        Last resort drug
  - - - Treats eye infections in AIDS