USMLE

Aminoglycosides

1,990 views
Antibiotics / Antiparasitics
  1. Penicillin Overview
  2. Penicillinase-Sensitive vs. Penicillinase-Resistant Penicillins
  3. Anti-Pseudomonal Penicillins
  4. Cephalosporins Overview
  5. 1st Generation Cephalosporins
  6. 2nd Generation Cephalosporins
  7. 3rd Generation Cephalosporins
  8. 4th Generation Cephalosporins
  9. 5th Generation Cephalosporins
  10. Carbapenems
  11. Monobactams (Aztreonam)
  12. Vancomycin
  13. Aminoglycosides
  14. Tetracyclines
  15. Tigecycline
  16. Chloramphenicol
  17. Clindamycin
  18. Linezolid
  19. Macrolides
  20. Polymyxins
  21. Sulfonamides
  22. Dapsone
  23. Trimethoprim
  24. Fluoroquinolones
  25. Daptomycin
  26. Metronidazole
  27. Rifamycins (Rifampin, Rifabutin)
  28. Isoniazid
  29. Pyrazinamide
  30. Ethambutol
  31. Chloroquine

Summary

Aminoglycosides are a class of antibiotics that includes the drugs gentamicin, amikacin, streptomycin, and neomycin. These antibiotics work by binding to the 30S ribosomal subunit of bacteria to prevent bacterial protein synthesis. Aminoglycosides are notable for only treating aerobic organisms, since oxygen is required for drug uptake. Adverse effects of aminoglycoside antibiotics include ototoxicity, nephrotoxicity, and neuromuscular blockade or paralysis. Aminoglycosides are also teratogenic and should not be used during pregnancy. Finally, chemical modifications or attachments of chemical groups to the drug by bacterial enzymes are the main mechanism of antibiotic resistance.

Key Points

  • Aminoglycosides
    • Drug Names
      • Gentamicin
      • Amikacin
      • Neomycin
      • Streptomycin
      • Tobramycin
    • Mechanism
      • Irreversible binding to 30S subunit of bacterial ribosomes
        • Inhibits formation of initiation complex, translocation, and causes misreading of mRNA
        • Prevents bacterial protein synthesis
      • Synergistic effect with beta-lactam antibiotics
        • Penicillins inhibit bacterial cell wall synthesis, which enable entry of aminoglycosides into interior of bacterial cells
      • Bactericidal
    • Clinical Use
      • Requires O2 for uptake
        • Treats aerobic organisms only
      • Severe gram-negative rod infections
      • Bowel surgery infection prophylaxis (neomycin)
      • Streptomycin: Mycobacterium tuberculosis (2nd-line)
    • Adverse Effects
      • Nephrotoxicity
        • Can cause tubular necrosis
      • Ototoxicity
        • Presents with hearing loss and tinnitus
        • Risk compounded with loop diuretics (also cause ototoxicity)
        • Damage to CN VIII can also lead to vestibular ataxia and vertigo
      • Neuromuscular blockade
        • Seen with large doses or intrapleural administration
        • Contraindicated in patients with myasthenia gravis
      • Teratogenicity
    • Resistance
      • Enzyme modification of drug
        • Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
        • Attachment of these groups reduces access to ribosomes
        • Most of these enzymes are plasmid-encoded
        • Seen with Enterococcus