Aminoglycosides

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Give eg's of and indications for aminoglycosides. eg's: gentamicin, amikacin Indications: Severe infections, particularly those caused by Gram-negative aerobes (including Pseudomonas aeruginosa): • Severe sepsis, including where the source is unidentified • Pyelonephritis and complicated urinary tract infection • Biliary and other intra-abdominal sepsis • Endocarditis Aminoglycosides lack activity against streptococci & anaerobes (see Mechanisms of action), so should be combined with penicillin &/or metronidazole when the organism is unknown.
MOA of aminoglycosides. Aminoglycosides bind irreversibly to bacterial ribosomes (30S subunit) & inhibit protein synthesis. They are bactericidal (i.e. they kill bacteria), although this effect is likely to be due to additional mechanisms that are incompletely understood. Their spectrum of action includes Gram-negative aerobic bacteria, staphylococci & mycobacteria. Aminoglycosides enter bacterial cells via an oxygen-dependent transport system. Streptococci and anaerobic bacteria do not have this transport system, so have innate aminoglycoside resistance. Other bacteria acquire resistance through reduced cell membrane permeability to aminoglycosides or acquisition of enzymes that modify aminoglycosides to prevent them from reaching the ribosomes. As penicillins weaken bacterial cell walls, they may enhance aminoglycoside activity by increasing bacterial uptake.
SE's of aminogycosides. • Nephrotoxicity • Ototoxicity
CI's, cautions, & important interactions of aminoglycosides. CI's: • Should be avoided unless absolutely necessary in pt's with myasthenia gravis Cautions: • Need to carefully monitor plasma concentrations to prevent renal, cochlear and vestibular damage, particularly in neonates and the elderly and in pt's with renal impairment Important interactions: Ototoxicity is more likely if aminoglycosides are co-prescribed with loop diuretics or vancomycin. Nephrotoxicity is more likely if aminoglycosides are co-prescribed with ciclosporin, platinum chemotherapy, cephalosporins or vancomycin.
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