Aminoglycosides Flashcards
What is the mechanism of action of aminoglycosides?
Aminoglycosides bind to the 30S ribosomal subunit, interfering with the initiation complex of protein synthesis and causing misreading of mRNA, leading to faulty proteins. They also disrupt bacterial cell membranes at high concentrations. They are ineffective against anaerobes due to oxygen-dependent uptake.
Describe the spectrum of activity of aminoglycosides.
Aminoglycosides are primarily active against aerobic Gram-negative bacilli, including Pseudomonas. They have limited Gram-positive activity but can synergize with beta-lactams or vancomycin for serious Gram-positive infections. They do not work on anaerobes or atypicals. Streptomycin has specific uses, and neomycin is used topically or for bowel prep.
What are common mechanisms of bacterial resistance to aminoglycosides?
The most common mechanism is bacterial production of modifying enzymes that inactivate the drug. Other mechanisms include mutation of the ribosomal binding site and reduced drug uptake or increased efflux. Pseudomonas and Enterococci often use modifying enzymes to resist gentamicin.
Outline key pharmacokinetic features of aminoglycosides.
Aminoglycosides are not absorbed orally and are given IV/IM for systemic use. They distribute mainly in extracellular fluid, do not penetrate the CNS or eye well, and concentrate in the renal cortex and inner ear. Excretion is via the kidneys in unchanged form, requiring dose adjustment in renal impairment.
What major drug interactions exist with aminoglycosides?
Aminoglycosides have additive nephrotoxicity with other nephrotoxic drugs and increased ototoxicity risk with loop diuretics or other ototoxic drugs. They can potentiate neuromuscular blockade, so concurrent use with neuromuscular blocking agents should be avoided.
What are common clinical uses of aminoglycosides?
Gentamicin is used for severe Gram-negative infections, tobramycin for Pseudomonas, amikacin for multidrug-resistant Gram-negatives, streptomycin for specific cases like plague and TB, and neomycin for topical skin infections or bowel preparation.
In what situations are aminoglycosides contraindicated or to be used with caution?
Aminoglycosides are contraindicated in pregnancy due to fetal ototoxicity and should be used with caution in renal impairment and in patients with Myasthenia gravis. Caution is also advised with concurrent ototoxic/nephrotoxic drugs.
List major adverse effects of aminoglycosides.
Major adverse effects include nephrotoxicity, ototoxicity, and rare neuromuscular blockade. Nephrotoxicity is usually reversible if caught early, while ototoxicity can cause irreversible hearing loss and balance issues.
What is a useful mnemonic for aminoglycoside toxicity and examples?
“Mean GNATS caNNOT kill anaerobes”: Mnemonic for aminoglycosides and their toxicities. GNATS = Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin; NOT = Nephrotoxicity, Ototoxicity, Teratogenic (plus Neuromuscular blockade).
