Lec 4 Cephamycins/Carbapenems/Glycopeptides/Etc Cushman Flashcards
the cephamycins have a _________ group which inc stability vs beta lactamases
a. oxime ether
b. pyridinium ring
c. C-3 carboxylic acid
d. 7a-methoxyl group
d. 7a-methoxyl group
drug with similar reaction to disulfiram
a. cephalexin
b. cefotetan
c. cilastatin
d. dicloxicillin
b. cefotetan
cefotetan releases _________, which can cause hypoprothrombinemia, and can also cause a disulfiram like rxn
a. 7alpha-methoxyl
b. a pyrimdine ring
c. N-methylthiotetrazole
d. a phosphate group
c. N-methylthiotetrazole
why is thienamycin not used as a drug but imipenem is?
too reactive to be used as a drug, since the primary amino group attacks the beta lactam intermolecularly
imipenim is the N-formiminoyl derivative of _______
a. azithromycin
b. daptomycin
c. thienamycin
d. plazomicin
c. thienamycin
The carbapenems are carbon analogs of the ________. The sulfur that is present in the thiazolidine ring of the penicillins is replaced by a ________ group. This increases reactivity because it is smaller than a sulfur, so the ring strain is greater in the carbapenems.
penicillins; methylene
Besides reacting with penicillin-binding proteins, imipenem reacts with and inhibits _______ _______
beta lactamases
what drug is commonly given with imipenem?
cilastatin
dehydropeptidase-1 inhibitor drug
cilastatin
Imipenems and other drugs in the carbepenem class are commonly referred to as “______ ______”, and their use is typically restricted in order to avoid widespread bacterial resistance
magic bullets
why are they called monobactams?
one ring, the beta lactam ring is not fused to any other ring
monobactams target almost completely gram _______ bacteria
negative
two glycopeptides antibiotics in clinical use
vancomycin (USA)
teicoplanin (Europe)
Vancomycin is an inhibitor of Gram _______ cell wall biosynthesis.
positive
vancomycin inhibits the _________ rxn that is required for cross-linking, but a different MOA than beta-lactam antibiotics
transpeptidase
difference between bactericidal and bacteriostatic
bactericidal kills bacteria, bacteriostatic slows growth
for vancomycin, a bacterium with an MIC ___ µg/mL is considered a susceptible strain. Staphylococcus strains that are methicillin-resistant are usually inhibited with MIC values ___-___ µg/mL.
4; 1-5
Vancomycin-resistant enterococcal (VRE) infections first appeared in Europe in connection with the use of _______
a. avoparcin
b. probenecid
c. oritavancin
d. dalfopristin
a. avoparcin
Vancomycin resistance appears to be due to a mutation of the peptidoglycan cell wall precursor from D-Ala-D-Ala to D-Ala-D-_______.
a. D-gly
b. D-pro
c. pyruvate
d. lactate
d. lactate
vanc is ___% elim by glomerular filtration with a half-life of ___-___ hours
90%; 4-11
vancomycin therapeutic uses (2)
- C diff pseudomembranous colitis (relapse or unresponsive to metronidazole tx)
- MRSA
red man syndrome is assoc with which antibiotic that we talked about?
vanc
nephrotoxicity and _______ are two rare potential problems of vanc
ototoxicity
oritavancin, telavancin, and dalbavancin are in what drug class?
lipoglycopeptide antibiotics
which of the following can be used in single dose regimens due to long half-life? (2 of them)
a. vancomycin
b. telavancin
c. dalbavancin
d. oritavancin
c. dalbavancin
d. oritavancin
MOA of telavancin and dalbavancin
identical to vancomycin. It binds to the D-Ala-D-Ala residue on growing peptidoglycan chains and inhibits transpeptidation and transglycosylation
synercid is a mix of ___% quinupristin and ___% dalfopristin
30%; 70%
The parent natural product mixture of pristinamycins lacks suitable solubility for reliable dosages. The derivatives quinupristin and dalfopristin have amino side chains that allow salt formation and enhance the _____ _____ needed to make a useful formulation.
water solubility
T or F: quinupristin and dalfopristin are each bacteriocidal alone
F (bacteriostatic)
Synercid is bacteriostatic against _______ _______ (bug) and bactericidal against strains of methicillin-susceptible and methicillin-resistant _______ (bug)
enterococcus faecium; staphylococci
dalfopristin MOA
directly interferes with peptidyl transferase forming a peptide bond between AAs
_______ binds in the ribosomal tunnel and causes blockage of the tunnel
a. dalfopristin
b. quinupristin
b. quinupristin
Synercid therapeutic use (3)
- vanc resistant enterococcus faecium bacteremia
- vanc-resistant enterococcus faecium UTIs
- skin infections caused by MRSA
quinupristin’s MOST COMMON mech of resistance is due to:
a. A2058 methylation in 23S rRNA
b. G2576U substitution
c. inc efflux pumps
d. A2058G substitution
a. A2058 methylation in 23S rRNA
Synercid significant SE
none (only mild ones)
which of the following is TRUE about the PK of Synercid?
a. average half life is 10 hours
b. the blood/brain or placental barriers are penetrated
c. clearance is 75% through biliary excretion (fecal matter) and the rest in urine
c. clearance is 75% through biliary excretion (fecal matter) and the rest in urine
quinupristin metabolism two products
quinupristin glutathione conjugate
quinupristin cysteine conjugate
dalfopristin metabolism leads to a _____ product and a pristinamycin IIA _____ product
hydrolysis; reduction
linezolid drug class
oxazolidinones
linezolid MOA
interacts with 50S subunit which prevents formation of 70S initiation complex. Specifically interacts with 23S rRNA
linezolid therapeutic uses (3)
- vanc-resistant enterococcus faecium
- nosocomial pnemonia causes by MRSA
- skin infections caused by MRSA
T or F: To reduce the development of drug-resistant bacteria and maintain the effectiveness of linezolid, it should be used only to treat/prevent infections that are proven or strongly suspected to be caused by multiple drug-resistant Gram-(+) bacteria, or when patients are allergic to otherwise effective alternatives.
T
linezolid resistance is due to ?
G to U substitution in PTC of 23S rRNA at position 2576
T or F: linezolid-induced neuropathy was reported amongst pts receiving linezolid for more than 12 months
F (6 months)
tongue discoloration and thrush are SE of which drug?
a. quinupristin
b. linezolid
c. telavancin
d. vancomycin
b. linezolid
most freq SE of linezolid (3 of them)
N/V/D
linezolid is metabolized via _____ _____ _____
morpholine ring oxidation
how many major metabolites are there for linezolid?
2
T or F: linezolid is a MAO inhibitor
T
which of the following statements is FALSE about Tedizolid Phosphate?
a. Tedizolid phosphate is a second-gen oxazolidinone used for tx of acute bacterial skin and skin structure infections
b. It is less potent than linezolid vs MRSA
c. Same MOA as linezolid
d. Oral or IV
e. Prodrug
f. Don’t consume high tyramine diet when taking
b. It is less potent than linezolid vs MRSA (more)
