Pharm - Streptogramins, cloramphenicol, oxazolidinones Flashcards
name the drug under “streptogramins” category (both brand and generic)
what is the ratio
SYNERCID:
quinupristin/dalfopristin
around 30% quinupristin and around 70% dalfopristin
explain the structures of quinupristin/dalfopristin and what this says about their activity
BULKY
not given orally - given IV
ALSO cannot get through gram negative membrane, so only active on gram (+) cocci
explain the MOA of quinupristin/dalfopristin
include if static or cidal
bind 50s ribosomal subunit to inhibit protein synthesis
quinupristin binds at the same site as macrolides!! dalfopristin binds at a NEARBY site. this results in a conformational change at the 50s ribsosome, SYNERGISTICALLY ENHANCING THE BINDING OF QUINUPRISTIN
bactericidal - concentration dependent
how do the streptogramins (quinupristin/dalfopristin) exhibit synergy
once dalfopristin binds nearby to the binding site of quinupristin (same as macrolides) it makes it easier for quinupristin to bind due to a conformational change in the 50s ribosome
________ directly interferes with polypetide chain formation
dalfopristin
true or false
the streptogramins are bactericidal, time dependent
FALSE
bactericidal time dependent
streptogramins are largely INACTIVE against what?
gram negative!!!
bc of bulky structure - can’t get thru membrane
3 resistance mechanisms to synercid
-MLS-B type resistance (modification of quinupristinbinding site)
-increased efflux
-enzymatic inactivation of dalfopristin
how is synercid administered and why
BULKY - only IV infusion
how are streptogramins eliminated
fecal
big DDI concern with streptogramins
they inhibit CYP3A4 – can increase the concentrations of a lot of drugs
clinical uses of streptogramins
not rly used. only used for serious infections associated with vanco resistant bacteremia, or complicated SSTI infections caused by staph or strep pyogenes
adverese effects streptogramins
just infusion-related events like pain and phlebitis at infusion site
can you give any MLS antibiotic with chloramphenicol??
tho cloramphenicol isnt part of MLS, still shouldnt be given together bc binding site very similar - one or the other won’t work
explain the MOA and spectrum of cloramphenicol
include whether static or cidal
reversibly binds 50s ribosomal subunit at p site and inhibits transpeptidation – VERY CLOSE to active site of macrolides and clindamycin (that’s why cant give MLS with chloramphenicol – interfere with each other)
bacteriostatic
broad spectrum - aerobic/anaerobic (+), (-)
which is better for rickettsiae and why - tetracyclines or cloramphenicol
both will be active against rickettsiae, but tetracyclines are better because they are safer
name 1 thing cloramphenicol will not be active against
chlamydiae
2 methods of cloramphenicol resistance
which is main?
main – cloramphenicol acetyltransferases (plasma encoded) – same resistance mech to fluoroquinolones
minor - decreased entry
how can cloramphenicol be administered
pretty smol molecule, so oral or IV is fine
ADMINISTERED AS PRODRUG
as mentioned, chloramphenicol is administered as a prodrug
explain how this differs from oral route to IV route
oral - chloramphenicol palmitate
parenteral - chloramphenicol succinate
explain chloramphenicol metabolism
both phase 1 (reduction) and phase 2 (glucuronidation)
how is distribution of chloramphenicol
GOOD even gets to brain and CSF
name AE’s of chloramphenicol
the AE’s are why its not used anymore - there’s a lot
NVM
bc broad spec - oral or vaginal candidiasis
aplastic anemia
gray baby syndrome
inhibits CYPS!
explain the symptoms of gray baby syndrome
vomiting, flaccidity, hypothermia, SHOCK, gray color, vascular collapse
caused by giving chloramphenicol in infants bc they dont have glucuronidation pathway fully developed
name 3 things chloramphenicol can clinically be used for
-serious rickettsia infections
-bacterial meningitis when allergic to pen
-topically for eye infection (not a lot systemically absorbed so AE not big concern)
generally – LAST RESORT BC OF SIDE EFFECTS
name 2 oxazolidinones
linezolid
tedizolid
explain the MOA of oxazolidinones
binds P site at 23S rRNA of the 50s ribosomal subunit
this prevents the formation of the larger ribosomal complex (fMet-tRNA)
THEREBY PREVENTING THE INITIATION (1st step) of protein synthesis
explain the spectrum of oxazolidinones
NOT active against (-) – only gram positive
are oxazolidinones static or cidal
static
(only cidal against streptococci)
true or false
oxazolidinones are active against mycobacterium tuberculosis
TRUE
(remember - linezolid is tuberculosis med)
1 resistance mechanism to oxazolidinones
mutation of linezolid binding site on 23S rRNA
general clinical uses of oxazolidinones
RESERVED FOR DRUG RESISTANT BACTERIA
really not used aside from that
ie- for CAP and healthcare associated pneumonia which doesnt respond
vanco resistant infections
multi-drug ressitant tuberculosis, etc
how are oxazolidinones administered
orally - have 100% bioavailability
how are oxazolidinones metabolized
oxidation
4 big AE of oxazolidinones
-thrombocytopenia (dec platelets)
-optic neuritis
-peripheral neuropathy
-linezolid is weak, irreversible inhibitor of MAO A and B — CAN POTENTIATE EFFECTS OF SEROTONERGIC, ADRENERGIC, AND DOPAMINERGIC AGENTS!!!!!! (serotonin syndrome) also can increase BP potentiation with tyramine
