Aminoglycosides

AMINOGLYCOSIDES

Gentamicin
Neomycin
Streptomycin
Netilmicin
Amikacin
Kanamycin
Tobramycin

Mechanism of action

• Aminoglycosides are bactericidal
• Initial site of action is the outer bacterial cell membrane
• Antibiotic molecules create fissures in the cell membrane
• Bind to the 30s ribosome and inhibit bacterial protein synthesis
• NB Aminoglycoside uptake into bacteria cells is active. Anaerobes have less energy available for this uptake, so aminoglycosides are less active against anaerobes
• NB Exhibit rapid concentration-dependent killing action

Indications

• Gram-negative sepsis

• Complicated skin, bone or soft tissue infection
• Complicated UTI
• Septicemia
• Peritonitis
• Severe pelvic inflammatory disease
• Endocarditis
• Mycobacterium infection
• Neonatal sepsis

Distribution

• Poorly absorbed from GI tract
• Primarily distributed in EC fluid – tissue concentration is much less than in plasma
• Exception is urine, otic perilymph and renal cortical tissue

Excretion

• Excreted unchanged (ie not metabolised) into the urine by glomerular filtration
• Plasma half-life 2-3 hrs (much higher with renal impairment and in elderly)
• NB half-life in renal cortex approx 100hrs, half-life in patients with renal dysfunction 30-60 hrs

Side effects and Drug Interactions

• Nephrotoxiticy
  • Usually reversible
  • Caused by renal cortical accumulation, binding to the brush border of the tubular epithelium resulting in proximal convoluted tubular cell degeneration and sloughing
  • NB Risk Factors for Nephrotoxicity
  • Modifiable - diuretics, IVcontrast exposure, hypovolaemia, ACE inhibitors, NSAIDs, other nephrotoxic medications
  • Non-modifiable – age, renal dysfunction
• Ototoxity
  • Usually irreversible
• Neuromuscular blockade
• Parasthesia
• Peripheral neuropathy
• Hypersensitivity reactions