Pharm - Aminoglycosides, Mupirocin, and Retapamulin Flashcards
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
true or false
aminoglycosides are not active against gram (+) MSSA
false - they are, it’s just not that good agaisnt it
beta lactams preferred
true or false
aminoglycosides are not active against anaerobic bacteria
TRUE
really only best against aerobic gram (-)
using aminoglycosides with ________ gives synergy
beta lactams
aminoglycosides are used almost exclusively for what
serious and life threatening NOSOCOMIAL infections
aminoglycosides can be used topically for what
ocular (eye) and external ear infections
3 main toxicities of aminoglycosides
ototoxicity
nephrotoxicity
potentiation of neuromuscular blockade
explain the ototoxicity of aminoglycosides
can cause hearing loss as well as vestubular damage (affects balance)
which 3 aminoglycosides are the most ototoxic?
which 2 are the most vestibulotoxic?
ototoxic – neomycin, kanamycin, amikacin
vestibular - streptomycin, gentamicin
which 3 aminoglycosides are the most nephrotoxic
neomycin
tobramycin
gentamicin
aside from aminoglycosides, what other antibiotics can potentiate the neuromuscular blockade
tetracyclines and clindamycin
are aminoglycosides used in pregancy
NO - because of all the AE
recap - which subunit do aminoglycosides bind and how do they bind
irreversibly bind 30s
true or false
aminoglycosides are not potent against gram (-) aerobes
FALSE - they are
mupirocin is for _______ use only
topical
MOA mupirocin
inhibits protein synthesis by reversibly binding and inhibiting isoleucyl tRNA synthase
without isoleucine - can’t synthesize proper proteins
is mupirocin static or cidal
against what bacteria
cidal against MANY (+) and select (-)
resistance mechanism to mupirocin
mutated isoleucyl tRNA synthase (plasmid-mediated)
name some specific clinical uses for mupirocin
-traumatic skin lesions and IMPETIGO infected with staph aureus or strep pyogenes
-nose ointment to eradicate staph aureus nasal carriage
AE of mupirocin
not a lot - it’s topical
but can cause irritation and sensitivity at application site
what is retapamulin used for
like mupirocin - an ointment for impetigo
MOA of retapamulin
binds unique site on 50s subunit
selectively inhibiting protein synthesis
retapamulin is a semisynthetic ______ derivative
pleromutilin
retapamulin is effective in the treatment of uncomplicated……. caused by……
superficial skin infections caused by groups A and B hemolytic streptococci and staph aureus (NOT MRSA)
