C.13.Aminoglycosides Flashcards
In what case do we give monotherapy of Aminoglycosides?
pyelonephritis
in any other case–> given in combination
mechanism of action of Aminoglycosides
binds to the 30s ribosomal subunit and interfere with protein synthesis by:
- blocking formation of the initiation complex
- inducing misreading of mRNA–>non-functional protein
- inhibiting translocation
what kind of killing action do aminoglycosides have?
concentration-dependent
what kind of killing action do penicillins and cephalosporins have?
time-dependent
are aminoglycosides bactericidal or bacteriostatic?
bactericidal
toxicity of aminoglycosides is both concentration-dependent and..
time-dependent
what does Post-antibiotic effect (PAE) mean?
killing action continues after plasma levels have declined below the MIC
What does Concentration-dependent killing action mean?
the antibacterial effect is increased proportionally above the MIC
What does time-dependent killing action mean?
independent of concentration, continuous as long as blood levels are maintained above the MIC
What are the side effects of aminoglycosides? (5)
“NO TAN”
Nephrotoxicity
Ototoxicity
Teratogenicity –> fetal ototoxicity
Allergic skin reaction–> contact dermatitis
Neuromuscular blockade
which Aminoglycoside has the broadest Spectrum? (least resistant)
Amikacin
which aminoglycoside is too toxic for systemic use (injection)?
Neomycin
extremely nephrotoxic
what is Paromomycin and what is it used for?
luminal-active agent
used against intestinal parasites (Entamoeba histolytica)
list the Aminoglycosides
“Mean” (a”min”oglycoside) GNATS cannot kill anaerobes
Gentamicin Neomycin Amikacin Tobramycin Streptomycin *Netilmicin *Kanamycin
nnot–> Nephrotoxicity, neuromuscular blockade
ototoxicity, teratogenicity
what is the spectrum and clinical use of GNAT (Gentamycin, Netilmicin, Amikacin, Tobramycin)?
- Aerobic gram - (E.coli, Enterobacter, Klebsiella, proteus, pseudomonas, Serratia)
- in combination with β-lactam AB:
- Enterococci (with penicillin)
- Pseudomonas (with 3rd gen’ cephalosporin)
what is the spectrum and clinical use of Streptomycin?
in combination with penicillin:
TB (2nd line agents), Tularemia, plague
Enterococcal endocarditis
uses of Neomycin
used to suppress intestinal flora before bowel surgery (oral)
topical use–> ear infections (ear drops)
what is Spectinomycin?
not an aminoglycoside but have similar mechanism
what are the mechanisms of resistance of Aminoglycosides
- plasmid-encoded inactivating enzymes (acetylation of the drug)
- alteration of ribosomal binding site
- intrinsic resistance of anaerobes - can’t penetrate the cell, requires O₂
which aminoglycoside may be active against some gentamicin-resistant and tobramycin-resistant bacteria?
Netilmicin
how are ‘GANTS’ given?
parenteral
what is the T1/2 of ‘GANTS’?
2-3hours
what type of elimination occurs in aminoglycosides
renal
directly proportional to creatinine clearance
dosing regimens of Aminoglycosides?
2-3 times daily, or once
