aminoglycoside
Summary
Aminoglycosides (e.g., gentamicin, tobramycin, amikacin, streptomycin, neomycin) are bactericidal antibiotics that inhibit bacterial protein synthesis by binding the 30S ribosomal subunit, causing misreading of mRNA. They are primarily used for severe Gram-negative infections and require oxygen for uptake, making them ineffective against anaerobes. Key toxicities include nephrotoxicity, ototoxicity, and neuromuscular blockade.
Detail
Mechanism: Aminoglycosides irreversibly bind the 30S ribosomal subunit, inhibiting the formation of the initiation complex and causing misreading of the genetic code, leading to inhibition of protein synthesis and bactericidal activity. Uptake into bacterial cells requires an oxygen-dependent transport system, which explains why aminoglycosides are ineffective against anaerobic organisms and have reduced efficacy in anaerobic environments (e.g., abscesses).
Clinical use: Primarily used for serious aerobic Gram-negative rod infections (e.g., Pseudomonas, E. coli, Klebsiella). Often used synergistically with beta-lactams or vancomycin for Gram-positive infections (e.g., enterococcal/streptococcal endocarditis) because cell wall-active drugs enhance aminoglycoside uptake. Neomycin is used for bowel prep and hepatic encephalopathy (oral, poorly absorbed). Streptomycin is used for tuberculosis (second-line) and plague.
Resistance: Bacterial production of aminoglycoside-modifying enzymes (acetyltransferases, phosphotransferases, adenylyltransferases) that alter drug structure and prevent ribosomal binding is the most common mechanism.
Toxicity: - Nephrotoxicity (especially with concurrent use of other nephrotoxic drugs like cephalosporins, cyclosporine, or vancomycin) — due to accumulation in renal proximal tubule cells. - Ototoxicity (vestibular and/or cochlear) — enhanced by concurrent loop diuretic use (e.g., furosemide); can be irreversible. - Neuromuscular blockade — can exacerbate myasthenia gravis; caution in patients with pre-existing neuromuscular disorders. - Teratogenic (Pregnancy category D).
Pharmacokinetics: Poor oral absorption (must be given IV/IM except for local/bowel effects); does not cross into CSF well. Monitoring of peak and trough levels is important due to narrow therapeutic index.
Mnemonic: 'Mean GNATS caNNOT kill anaerobes' - Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin.
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- Sketchy Pharm - Aminoglycosides
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