Pharm 101: Gentamicin

Class

Aminoglycoside antibiotic

Pharmacodynamics
  • Passive diffusion into cell via porin channels across outer membrane, then oxygen-dependent active transport into cytoplasm
    • Active transport is enhanced by cell wall active drugs such as penicillin and vancomycin (synergistic effect)
    • Low ECF pH and anaerobic conditions inhibit transport by reducing gradient
  • Binds to 30S subunit of ribosomal proteins and irreversibly inhibits protein synthesis (bactericidal) by:
    • Interfering with initiation complex of peptide formation
    • Inducing misreading of mRNA thus producing non-functional protein
    • Causing break up of polysomes into non-functional monosomes
  • Exhibits concentration-dependent killing and a post-antibiotic effect
  • Mechanisms of aminoglycoside resistance:
    • Transferase enzyme that inactivates drug
    • Impaired entry of drug into cell
    • Alteration/deletion of 30S ribosomal subunit receptor protein
Pharmacokinetics
  • IV, IM, topical administration
  • Absorption:
    • Well absorbed
  • Distribution:
    • Small volume of distribution
    • 10% plasma protein bound
    • Doesn’t reach CNS and eye readily
  • Metabolism:
    • Not metabolised
  • Elimination:
    • Renal excretion. Glomerular filtration
    • Half-life 2-3 hours in normal renal function, 24-48 hours in significant renal impairment
Antimicrobial activity
  • Aerobic gram negative bacteria:
    • E Coli
    • Pseuodomonas, Enterobacter
    • Proteus, Klebsiella, Serratia
  • Gram positive bacteria: (with beta lactams or vancomycin)
    • Staph
    • Strep
  • No activity against anaerobes
Adverse effects
  • Reversible nephrotoxicity
    • Acute tubular necrosis
  • Irreversible ototoxicity
    • 1-5% receiving gentamicin for more than 5 days
    • Mainly vestibular dysfunction, although loss of hearing can also occur
  • Neuromuscular blockade in high doses
Precautions/contraindications
  • Administration with loop diuretics potentiates nephrotoxicity
Benefits of once daily dosing
  • Just as effective, and probably less toxic, than multiple smaller doses
  • Concentration-dependent killing: kills increased number of bacteria at more rapid rate at higher concentration
  • Post-antibiotic effect: effects last longer than detectable serum level
  • Reduced toxicity: decreased time above toxic threshold concentration
  • Practical advantages:
    • Less nursing time
    • OPD therapy possible
    • Drug level not required unless > 3 day therapy
References
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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