Aminoglycoside

Aka: Aminoglycoside, Kanamycin

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II. 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. Klebsiella Pneumoniae
    4. Proteus species
    5. Serratia
    6. Pseudomonas

III. Mechanism

  1. Anti-Ribosomal Antibiotic (Bactericidal, Protein Synthesis Inhibitor)
    1. Aminoglycosides undergo oxygen dependent active transport into the Bacterial cytoplasm where they concentrate
      1. Aminoglycosides are potentiated by Beta Lactams which break down Bacterial cell walls
    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

IV. Medications: Actively Used Systemic Antibiotics

  1. Amikacin
    1. Broadest Gram Negative Bacteria spectrum of the Aminoglycosides (including Pseudomonas)
  2. Gentamicin
    1. Most commonly used of the Aminoglycosides
  3. Plazomycin
    1. Used in complicated, drug-resistant Urinary Tract Infection (Enterobacteriaceae, ESBL, CRE)
  4. Streptomycin
    1. Oldest of the Aminoglycosides (and significant Antibiotic Resistance has developed)
  5. Tobramycin
    1. Antipseudomonal coverage
    2. Used systemically and in nebulized form in Cystic Fibrosis
    3. Used topically in complicated Bacterial Conjunctivitis

V. Medications: Other

  1. Neomycin
    1. Topical Antibiotic use only (toxic when used systemically)
    2. Neomycin is found in Cortisporin Otic Suspension and triple Antibiotic ointment
  2. 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

VI. 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)

VII. 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 (rare)
    1. May increase Neuromuscular Blocker effect
    2. May exacerbate Myasthenia Gravis

VIII. 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

IX. 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/

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