aminoglycosides
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| aminoglycosides (8) | Streptomycin; Neomycin; Kanamycin; Tobramycin; Paromomycin; Gentamicin; Netilmicin; Amikacin
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| aminoglycosides commonly used systemically (3) | Tobramycin; Gentamicin; Amikacin
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| aminoglycoside mechanism of action | They interact with the 30S subunit of the ribosome and block protein synthesis; Aminoglycosides get into bacteria through porin proteins and electron transport (energy-dependent)
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| aminoglycoside concentrations | aminoglycosides are known to be rapidly bactericidal and this killing effect depends on the concentration of the drug (shoot for 5-6x MIC for Cmax)
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| resistance mechanisms for aminoglycosides (3) | 1) ribosomal resistance (mycobacteria); 2) resistance due to decreased drug uptake (anaerobes); 3) resistance caused by aminoglycoside modifying enzymes (**most important clinically) - strains will show higher MICs than strains of same species w/o upregul
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| aminoglycoside spectrum | potent against gram negatives (enterococcus varies); not very active against gram positives except staph
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| aminoglycosides with beta-lactams results in | synergy (common for endocarditis)
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| aminoglycoside with chloramphenicol results in | antagonism
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| aminoglycoside PK | very polar - poorly absorbed orally (1%) so given IV; distributed poorly but accumulate in high levels in kidneys; not metabolized - excreted unchanged
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| aminoglycosides toxicities (3) | 1) neuromuscular blockade; 2) ototoxicity; 3) nephrotoxicity
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| aminoglycoside toxicity mechanism | drug enters cell lysosome, inhibits mitochondrial function and Na/K ATPase, cell swells and ruptures
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| aminoglycoside toxicity time course | only observable after 5-7 days of therapy
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| aminoglycoside toxicity reversibility | nephrotoxicity usually reversible after D/C; ototoxicity not always reversible (depends on extent of damage; vestibular damage usually permanent)
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| aminoglycoside toxicity - comparisons among them for ototoxicity | netilmicin the least toxic; rest are equal
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| aminoglycoside toxicity - comparisons among them for nephrotoxicity | Gentamicin>tobramycin>amikacin>netilmicin
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| concentrations at risk for oto/nephrotoxicity with aminoglycosides | > 2 mg/L (gentamicin/tobramycin) or 8-10 (amikacin)
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| Gentamicin specifics | used to treat serious infection of gram negative bacilli. Most gentamicin-resistant strains are cross resistant to tobramycin but are susceptible to amikacin. It is more nephrotoxic than tobramycin, but roughly equivalent in ototoxic potential.
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| Tobramycin specifics | similar to gentamicin except that it is much less active against enterococci, Tobramycin is not active against mycobacteria.
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| Amikacin specifics | Resistant to most of the aminoglycoside modifying enzyme; broadest spectrum of activity; use should be limited to severe infections by strains suspected of being resistant to gentamicin and tobramycin
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| Netilmicin specifics | newest of the aminoglycosides in the market. More resistant to aminoglycoside modifying enzyme and less toxic than gentamicin.
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| Kanamycin specifics | given orally to kill the bowl flora prior to intestinal surgery.
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| Neomycin specifics | very nephrotoxic, and is no longer administered parenterally. The primary use is in the topical treatment of superficial infection of the skin and eye
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| Streptomycin specifics | role has declined; can used in combination with a penicillin to treat bacterial endocarditis due to S. viridans and enterococcus; still used for tuberculosis and other uncommon infections (plague, brucellosis…).
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| Paromomycin specifics | used only for treating intestinal amebiasis.
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