Pharm

Aminoglycoside

search

Aminoglycoside, Kanamycin

  • See Also
  1. Amikacin
  2. Gentamicin
  3. Kanamycin
  4. Plazomycin
  5. Streptomycin
  6. Tobramycin
  • Indications
  1. Activity
    1. Aerobic and facultative Gram Negative Rods
    2. NO anaerobic activity
      1. Aminoglycosides require oxygen for active transport into Bacterial cells
  2. Organisms
    1. Enterobacter
    2. Escherichia coli
    3. KlebsiellaPneumoniae
    4. Proteus species
    5. Serratia
    6. Pseudomonas
  • Mechanism
  1. Bactericidal, Protein Synthesis Inhibitor
    1. Aminoglycosides undergo oxygen dependent active transport into the Bacterial cytoplasm where they concentrate
    2. Binds 70s Bacterial ribosome at the interface between its 30s and 50s subunits
    3. Results in mis-reading of Bacterial mRNA and defective Bacterial Proteins
  2. Antibiotic Resistance mechanisms
    1. Decreased Bacterial cell permeability and decreased active transport of Aminoglycosides into Bacterial cells
    2. Bacterial enzymatic degradation of Aminoglycosides
    3. Binding site mutations
  • Medications
  • Active
  1. Amikacin
  2. Gentamicin
  3. Plazomycin
  4. Streptomycin
  5. Tobramycin
  • Medications
  • Other
  1. Kanamycin
    1. Kanamycin is not typically used in U.S., however, Amikacin is derived from Kanamycin A
    2. Kanamycin is an Antibiotic complex extracted from Streptomyces kanamyceticus (found in Japanese soil)
    3. Kanamycin complex has three components (A, B, C) of which only Kanamycin A has significant medical use
  • Pharmacokinetics
  1. Renal excretion unchanged in urine
  2. Not distributed to the eye or Central Nervous System
  3. Parenteral use, inhaled (Tobramycin in CF) or topical use (otic Antibiotics, Ophthalmic Antibiotics)
    1. Aminoglycosides have no significant oral Bioavailability (other than Kanamycin)
  • Adverse Effects
  1. Nephrotoxicity
    1. See risk factors below
  2. Ototoxicity
    1. Risk of permanent Deafness
    2. With higher Aminoglycoside peak concentrations
    3. Increased risk in Mitochondrial DNA mutations (e.g. m.1555A>G)
  3. Neuromuscular Blockade
    1. May increase Neuromuscular Blocker effect
    2. May exacerbate Myasthenia Gravis
  • Risk Factors
  • Nephrotoxicity
  1. Advanced age
  2. Prior Renal Insufficiency
  3. Dehydration
  4. Hypokalemia
  5. Hypomagnesemia
  6. Liver disease
  7. Sepsis
  8. Drug Interactions with other nephrotoxic medications
    1. Cephalothin (Keflin) and other Cephalosporins
    2. Cyclosporin A
    3. Cisplatin
    4. NSAIDS
    5. ACE Inhibitors
    6. Methoxyflurane
    7. Loop Diuretics
    8. Amino Acids
  • References
  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 112-3
  2. Block (2023) Aminoglycosides, StatPearls, Treasure Island, Fl
    1. https://www.ncbi.nlm.nih.gov/books/NBK541105/