Term
| Pharmacokinetics of Aminoglycosides (amikacin, gentamicin, tobramycin, streptomycin) |
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Definition
Poor oral absorption, preferred routes are IM or IV: 30-60 min IV infusion 2-3x daily;
Once a day dosing may now be preferred due to dose-dependent killing;
Polar drugs that do NOT readily enter cells --> do not penetrate eye or into CNS;
Concentrates in renal cortex & inner ear --> nephrotoxicity & ototoxicity;
Normal T1/2 = 2-3 hrs;
Renal Failure T1/2 = 24-48 hrs;
Adjust doses in renal failure; |
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Term
| aminoglycosides + penicillins (drugs that inhibit cell wall synthesis - cephalosporins, vacnomycin) |
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Definition
| synergistic killing effect |
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Term
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Definition
inhibit bacterial protein synthesis by IRREVERSIBLY binding to 30-S ribosomal subunit;
Blocks initiation of protein synthesis;
blocks movement of ribosome, causing 70-S ribosome to break up into subunits;
Cause misreading of mRNA code leading to production of mutant proteins that kill bacteria --> bactericidal effect continues after drug conc. drop below MIC |
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Term
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Definition
potentially IRREVERSIBLE side effect of aminoglycosides;
Increased risk with:
DON'T use with loop diuretics (furosemide, ethacrynic acid), vancomycin, elderly pts, dehydrated pts, high doses for long periods of time |
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Term
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Definition
| characterized by tinnitus and loss of hearing |
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Term
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Definition
| characterized by vertigo, ataxia, and loss of balance |
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Term
| nephrotoxicity (acute tubular necrosis) |
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Definition
occurs in proximal tubule cells;
usually REVERSIBLE;
causes rise in serum Cr;
measure Cr every 2-3 days;
Increased risk with:
higher doses for more than 5 days,
co-administration w/ vancomycin or a cephalosporin,
pts w/ pre-existing renal failure,
elderly & dehydrated pts |
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Term
| Side Effects/Toxicities of Aminoglycosides |
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Definition
| ototoxicity, nephrotoxicity, neuromuscular block |
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Term
| Resistance to Aminoglycosides |
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Definition
| bacterial enzymes that phosphorylate, adenylate, or acetylate the drug so that it is not capable of binding effectively to 30-S ribosome --> not capable of inhibiting protein synthesis |
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Term
| Spectrum of Activity of Aminoglycosides |
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Definition
LIMITED activity against gram (+) bacteria --> use w/antibiotics that inhibit cell wall synthesis (SYNERGISTIC - penicillins, cephalosporins);
BEST ACTIVITY against aerobic Gram (-) enteric bacteria (E.coli, Klebsiella, Proteus, P. auruginosa);
NOT active against ANAEROBIC bacteria |
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Term
| Clinical Uses of Aminoglycosides |
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Definition
Tx severe systemic infections caused by gram (-) enteric bacteria (e.g. sepsis);
Used in combo w/ bacterial cell wall wall synthesis inhibitor to treat bacterial endocarditis; |
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Term
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Definition
generally has less activity against gram (-) enteric bacteria;
USED TO TREAT BACTERIAL ENDOCARDITIS, specifically gentamicin-resistant enterococcal endocarditis |
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Term
| gentamicin (Garamycin, Jenamicin) |
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Definition
used in combo w/ beta-lactam antibiotic (ceph, penicillins) for UTIs;
used for HOSPITAL-ACQUIRED PNEUMONIA;
NOT recommended for CAP;
used with penicllin for enterococcal endocarditis;
Used to tx sepsis caused by gram (-) bacilli (P. aeruginosa) |
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Term
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Definition
better activity against P. aeruginosa to treat bacteremia, osteomyelitis, and pneumonia;
INHALATION dosage form ---> treats bronchopulmonary infections caused by P. aeruginosa in pts w/ cystic fibrosis |
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Term
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Definition
BROADEST antimicrobial spectrum;
resistant to many of bacterial enzymes that inactivate other aminoglycosides;
Uses:
Tx serious nosocomial (hospital) infections caused by gram (-) aerobic bacilli;
less active against enterococci, should NOT be used to treat enterococcal infections |
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