Pharm - Aminoglycosides, Mupirocin, and Retapamulin Flashcards
(48 cards)
name 8 aminoglycosides
amikacin
gentamicin
tobramycin
neomycin
streptomycin
kanamycin
sisomycin
netilmicin
briefly explain MOA of aminoglycosides
irreversibly bind 30s subunit
bactericidal concentration dependent
are streptomycins used orally?
explain why or why not
not used orally
have R-O-R glycosidic bond - will be hydrolyzed rapidly
really only used topically or IV
also very polar so not the best distribution
is treptomycin more active at alkaline or acidic pH?
alkaline
which aminoglycoside is least likely to be resistant? why?
amikacin
has a very large R group. other aminoglycosides can get modified at 5 positions, but aminoglycoside can only get altered at 1 position (#1 position)
which enzymes are capable of inactivating aminoglycosides at 5 different places
transferases
name 4 MOAS of aminoglycosides
- block initiation of protein synthesis
- block further translation and initiate premature termination - forms short proteins
- incorporate the incorrect amino acid
- breakup polysomes into monosomes (streptosomes)
which bacteria are aminoglycosides MOST active against
aerobic gram (-) bacteria
what are “streptosomes”
ribosomes that have aminoglycoside antibiotics bound to them
do aminoglycosides have gram (+) action?
their main action is against aerobic gram negative
that said, they are a little bit active against (+), but beta lactams are much better choices
if beta lactams and aminoglycosides used together - gives synergy!!!
which particular subunit do aminoglycosides bind
reversibly or irreversibly?
16s subunit of 30s ribosome
once bound - DOES NOT COME OFF - irreversible
true or false
aminoglycosides are bactericidal and irreversible protein synthesis inhibitors
TRUE
how do aminoglycosides enter the bacteria
through porin channels - energy dependent
TRUE OR FALSE
aminoglycosides do not have postantibiotic effect
FALSE - they fo
as mentioned, aminoglycosides are irreversible and bactericidal
are they conc or time dependent
concentration dependent
3 resistance mechanisms to aminoglycosides
which is MAJOR clinically
MAJOR - production of transferase enzyme that inactivates the aminoglycoside
- impair entry into cell – gram (-) decrease their porins
- receptor protein on 30s ribosomal subunit may be mutated
as mentioned, the major resistance mechanism against aminoglycosides is the production of transferase enzymes that inactivate the aminoglycoside antibiotic
name 3 enzymatic methods of this inactivation
AMPylation
acetylation
phosphorylation
aside from giving synergy, what is an advantage of administering a beta lactam with an aminoglycoside
will decrease the chance of developing resistance
how are aminoglycosides administered and why
IM/IV - NOT ORAL - bc poor oral absorption -highly polar so distribution not good
true or false
aminoglycosides have high distribution in the brain and CSF
FALSE - very low
bc so polar
if aminoglycosides need to reach high levels in the brain or CSF, what is done?
intrathecal/itnraventricular injection
however this is not rly done bc so painful — usually will use something else
explain the 2 alternative dosing of aminoglycosides
traditionally it’s 2-3 times a day
can give a high dose QD – this gives concentration dependent killing and post antibiotic effect
how are aminoglycosides excreted and why important
RENALLY
need to consider creatinine clearance when dosing
which 4 aminoglycosides have the widest spectrum
amikacin
tobramycin
gentamicin
netilmicin
