Antibacterials — Aminoglycosides

AMINOGLYCOSIDES

Mechanism of Action

• Permeates into the bacterial cell down electronegative gradient (negative interior) via O₂ dependent process
  • Can be retarded by acidic, anaerobic environments (abscess)
• Inhibits bacterial 30S ribosomal subunit
  • Inhibits bacterial protein synthesis
  • Inhibition of bacterial growth (bacteriostatic) → bacteriocidal
• Synergism with cell wall inhibitors (β lactam antibiotics)
  • Penicillins inhibit peptidoglycan synthesis → increased permeability to aminoglycosides → inhibition of protein synthesis (including penicillin binding protein) → Further increase in cell permeability → death
• Displays concentration dependent killing and post-antibiotic effect
  • Peak plasma aminoglycoside >8 MIC required
  • Large AUC not required

Antimicrobial Spectrum

• Strong activity against aerobic gram negative bacteria
• Effective against gram positives esp. with β lactam synergism
• Ineffective against obligate anaerobes

Pharmacokinetics

• Absorption
  • Poor GI absorption, UNLESS inflammation or ulceration
• Distribution
  • Vd approximating extracellular fluid
  • Poorly protein bound
  • Poor CNS, ocular penetrance
• Metabolism
  • Minimal metabolism
• Elimination
  • Renal clearance via filtration
  • T_1/2b 2~3 hours
  • Can be removed by dialysis