Katzung 12th ed - Chapter 45 - Aminoglycosides (1) Flashcards
Name at least two important aminoglycosides.
Gentamycin, Tobramycin, Streptomycin, Amikacin.
Name three fields of clinical use of aminoglycosides.
1) Gram negative sepsis, together with a beta-lactam
2) Gram positive endocarditis, synergistically with vancomycin
3) To treat tuberculosis
How do aminoglycosides get into the cytoplasm of the bacterial cell?
Consider gram negative bacteria. They move through the outer cell membrane by passive diffusion through porin channels. They are then actively transported across the inner cell membrane. This may be aided by concurrent administration of a penicillin, which will reduce bacterial cell wall integrity.
What does the aminoglycoside do once inside the bacterial cell?
It binds to the 30S subunit of the ribosome and inhibits protein synthesis (affecting translation of mRNA)
Describe the administration routes of aminoglycosides
IV or IM. Almost 0% absorbed via oral route.
Half-life of aminoglycosides?
2-3 hours. Up to 24-48hrs with significant renal impairment.
Describe the absorption of aminoglycosides in tissues.
Poor penetrance to the CSF. Levels in CSF will be a maximum of 20% the level in plasma.
Aminoglycosides exhitbit __________-dependent killing.
Concentration-dependent. (i.e. increasing concentrations will kill an increasing proportion of the bacteria at a more rapid rate). This is as opposed to time-dependent killing. It is for this reason that there is an argument for giving a large once-daily dose rather than bd or tds.
For gentamicin, a trough concentration of _________ is predictive of toxicity. What is the optimal trough level?
2mcg/mL. The trough concentration is measured between 18 and 24 hours after the daily dose is given. Less than 1mcg/mL is optimal.
What is the standard dose of gentamicin given to patients?
5-7mg/kg/day assuming normal renal function.
Describe the toxicity of gentamicin.
Ototoxic – manifesting mainly as vestibular dysfunction.
Nephrotoxic
If gentamicin is given without a beta-lactam, why is it not effective against gram-positive bacteria?
Because it cannot enter the cell. There are no porin channels.
What action does gentamicin have against anaerobes?
None. Active transport of gentamicin across the inner bacterial cell membrane is an oxygen-dependent process, which cannot occur in oxygen-deprived conditions.
Name a few gram negative bacteria for which an aminoglycoside would be effective.
Klebsiella, Pseudomonas, Enterobacter, Serratia, Proteus, Acinetobacter
Describe the resistance mechanisms of bacteria against aminoglycosides.
1) Abnormal porins / anaerobic conditions –> reduced penetrance
2) Modification of the ribosomal binding site
3) Enzymatic inactivation
