Pharm - Streptogramins, cloramphenicol, oxazolidinones

Question 1

name the drug under “streptogramins” category (both brand and generic)

what is the ratio

Answer 1

SYNERCID:
quinupristin/dalfopristin

around 30% quinupristin and around 70% dalfopristin

Question 2

explain the structures of quinupristin/dalfopristin and what this says about their activity

Answer 2

BULKY

not given orally - given IV

ALSO cannot get through gram negative membrane, so only active on gram (+) cocci

Question 3

explain the MOA of quinupristin/dalfopristin

include if static or cidal

Answer 3

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

Question 4

how do the streptogramins (quinupristin/dalfopristin) exhibit synergy

Answer 4

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

Question 5

________ directly interferes with polypetide chain formation

Answer 5

dalfopristin

Question 6

true or false

the streptogramins are bactericidal, time dependent

Answer 6

FALSE

bactericidal time dependent

Question 7

streptogramins are largely INACTIVE against what?

Answer 7

gram negative!!!

bc of bulky structure - can’t get thru membrane

Question 8

3 resistance mechanisms to synercid

Answer 8

-MLS-B type resistance (modification of quinupristinbinding site)

-increased efflux

-enzymatic inactivation of dalfopristin

Question 9

how is synercid administered and why

Answer 9

BULKY - only IV infusion

Question 10

how are streptogramins eliminated

Answer 10

fecal

Question 11

big DDI concern with streptogramins

Answer 11

they inhibit CYP3A4 – can increase the concentrations of a lot of drugs

Question 12

clinical uses of streptogramins

Answer 12

not rly used. only used for serious infections associated with vanco resistant bacteremia, or complicated SSTI infections caused by staph or strep pyogenes

Question 13

adverese effects streptogramins

Answer 13

just infusion-related events like pain and phlebitis at infusion site

Question 14

can you give any MLS antibiotic with chloramphenicol??

Answer 14

tho cloramphenicol isnt part of MLS, still shouldnt be given together bc binding site very similar - one or the other won’t work

Question 15

explain the MOA and spectrum of cloramphenicol

include whether static or cidal

Answer 15

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 (+), (-)

Question 16

which is better for rickettsiae and why - tetracyclines or cloramphenicol

Answer 16

both will be active against rickettsiae, but tetracyclines are better because they are safer

Question 17

name 1 thing cloramphenicol will not be active against

Answer 17

chlamydiae

Question 18

2 methods of cloramphenicol resistance

which is main?

Answer 18

main – cloramphenicol acetyltransferases (plasma encoded) – same resistance mech to fluoroquinolones

minor - decreased entry

Question 19

how can cloramphenicol be administered

Answer 19

pretty smol molecule, so oral or IV is fine

ADMINISTERED AS PRODRUG

Question 20

as mentioned, chloramphenicol is administered as a prodrug

explain how this differs from oral route to IV route

Answer 20

oral - chloramphenicol palmitate

parenteral - chloramphenicol succinate

Question 21

explain chloramphenicol metabolism

Answer 21

both phase 1 (reduction) and phase 2 (glucuronidation)

Question 22

how is distribution of chloramphenicol

Answer 22

GOOD even gets to brain and CSF

Question 23

name AE’s of chloramphenicol

Answer 23

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!

Question 24

explain the symptoms of gray baby syndrome

Answer 24

vomiting, flaccidity, hypothermia, SHOCK, gray color, vascular collapse

caused by giving chloramphenicol in infants bc they dont have glucuronidation pathway fully developed

Question 25

name 3 things chloramphenicol can clinically be used for

Answer 25

-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

Question 26

name 2 oxazolidinones

Answer 26

linezolid tedizolid

Question 27

explain the MOA of oxazolidinones

Answer 27

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

Question 28

explain the spectrum of oxazolidinones

Answer 28

NOT active against (-) -- only gram positive

Question 29

are oxazolidinones static or cidal

Answer 29

static (only cidal against streptococci)

Question 30

true or false oxazolidinones are active against mycobacterium tuberculosis

Answer 30

TRUE (remember - linezolid is tuberculosis med)

Question 31

1 resistance mechanism to oxazolidinones

Answer 31

mutation of linezolid binding site on 23S rRNA

Question 32

general clinical uses of oxazolidinones

Answer 32

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

Question 33

how are oxazolidinones administered

Answer 33

orally - have 100% bioavailability

Question 34

how are oxazolidinones metabolized

Answer 34

oxidation

Question 34

4 big AE of oxazolidinones

Answer 34

-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