Aminoglycosides Flashcards
What are the aminoglyccosides?
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Neomycin Tobramycin* Amikacin* Gentamicin* Streptomycin
*these are most frequently prescribed
MOA of Aminoglycosides?
- protein synthesis inhibitor, binds to 30S ribosomal subunit thus inhibiting synthesis.
- bactericidal: works on the outer cell membrane, creates fissures in the outer cell membrane leading to cell leakage and enhanced uptake of abx uptake.
Mechanisms of resistance (bug to aminoglycosides)
- transferase enzyme inactivates aminoglycoside
- impaired entry of aminogylcoside into the cell
- RECEPTOR protein on 30S ribosomal subunit may be deleted or altered.
Aminoglycosides
- distribution
- protein bound
- what % of drug is most often excreted unchanged in the urine?
- when is dose adjustment required for this med?
- poorly distributed, increased distribution in pt w/ ascites, burns, pregnancy, & Cystic Fibrosis
- poorly protein boud
- 99% is excreted unchanged, does not have significant metab.
- Dose adjustment is required in renal insufficiency but NOT required for hepatic disease.
- -typically need to use lower levels in kidney disease because it will build up in the kidney»>kidney damage.
Aminoglycoside Spectrum of Activity
-aerobic gram negative bacilli
most commonly Pseudomonas, Enterobaccter, Serratia, Acinetobacter, and Klebsiella
- used for mycobacterial infections and protozoa
- synergistic w/ beta lactams or other abx against gram positive cocci
- negligble anaerobic coverage
Are aminoglycosides time or concentration dependent killing?
-concentration dependent killing, increasing concentrations kill an increasing proportion of bacteria and at a more rapid rate.
What is postantibiotic effect?
- how long a medication is still active in your body even after youre done taking the medication.
May last for several hours, and varies w/ the type of bacteria.
Aminoglycosides clinical use
serious, life-threatening GRAM NEGATIVE infections
- sepsis
- peritonitis
- endocarditis
- mycobacterium infection
- severe pelvic inflamm disease
- ocular infections (topical)
- Respiratory Tract Infections
- Otitis externa (topical)
- Tularemia
what is empiric therapy?
-your best guess therapy
Gentamycin
- effective for gram -/+ bacteria?
- use in combo?
- Routes of administration
- effective for gram negative and some gram + (some resistance occurs)
- yes, almost always used in combo with another abc (beta-lactam)
- IV, IM, Topical, Ophthalmic
Torbramycin
- effective for gram -/+ bacteria?
- Routes of administration
- similar coverage to gentamycin (gram - and some gram +), except better pseudomonas coverage
- Inhalation (CF), IV, IM, Ophthalmis
Amikacin
- when is this most often used?
- Route of Administration
- used for resistant bacteria
- IV IM
Streptomycin
- effective for which specific bacteria?
- use in combo?
- Routes of administration
- 2nd line for TB
- used in combo w/ penicillin or ampicillin for endocarditis (some resistance has emerged)
- IM
Neomycin
- use
- resistance to what bacteria?
- which medication is most similar to Neomycin?
- limited to topical and oral use (bowel prep for surgery)
- resistance exists especially to Pseudomonas and Streptococci
- Kanamycin (IV, IM)
- this is one of the more toxic aminoglycosides.
Paromomycin
-use?
- intestinal amebiasis
- hepatic coma/encephalopathy
Aminoglycosides safe for pregnancy and breastfeeding?
- there is evidence of human risk but clinical benefits may outweigh the risk.
- aminoglycosides enter breast milk but are not well absorbed orally.
CI of Aminoglycosides
- previous allergy or hypersensitivity rxn
- Myasthenia gravis
What are the Black Box Warnings/Adverse effects of Aminoglycosides?
-nephrotoxicity: reversible, elevated troughs, monitor renal casts, urine output
-ototoxicity: both vestibular= manifests as vertigo, ataxia, loss of balance, tinnitus
and cochlear= high frequency hearing loss.
–Irreversible, elevated peaks
-neurotoxicity
-neuromuscular blockade: can produce curare-like neuromuscular blockage at very high doses give too fast resulting in respiratory paralysis. Reversible!
Aminoglycosides: How often do we monitor?
- Peak- 30min after infusion
- Troughs- 30minutes before next infusion
Aminoglycoside Drug Interactions:
- chemo agents Agalsidase Alfa/Beta
- Diuretics
- Neuromuscular Blocking
- Beta-lactam
- Vitamin K Antagonists
Chemo: gentamycin may diminish the effects of Agalsidase Alfa/Beta. Risk: X Avoid combination
Diuretics: enhance the adverse/toxic effects of aminoglycosides. Risk C: Monitor Therapy
NMJ: aminoglycosides may enhance the respiratory depressant effects of NMJ blocking drugs. Risk C
Beta Lactam: synergistic effects, cephalosporins can increase nephrotoxicity
Vit K antagonist: (warfarin) may enhance anticoagulant effect of Vit. K Antagonists. Risk C Monitor therapy
