Lec 5 Aminoglycosides/Macrolides Cushman Flashcards
aminoglycoside 2 core structures
streptidine
2-deoxystreptamine
which of the following are NOT aminoglycosides? (2 of them)
a. tobramycin
b. erythromycin
c. plazomicin
d. amikacin A
e. clarithromycin
f. gentamicin C2
g. neomycin B
h. streptomycin
b. erythromycin
e. clarithromycin
4 main things for mechanism of aminoglycosides
-inhibits formation of initiation complex
-blocks further translation
-premature termination of transcription
-impairment of proofreading and formation of “nonsense proteins”
aminoglycosides bind to the ____ subunit of the ribosome
30S
what do the “nonsense proteins” formed by aminoglycosides do?
impair bacterial cell wall function
aminoglycoside antibiotics can affect the 30S ribosomal subunit to cause a _______ mutation
frameshift
which class of antibiotics affects normal codon-anticodon binding?
aminoglycosides
bacterial aminoglycoside uptake: passage through the cytoplasmic membrane is an _______ transport process
active
bacteria inactivate aminoglycosides by all of the following EXCEPT
a. acetylation
b. adenylation
c. phosphorylation
d. oxidation
d. oxidation
3 aminoglycoside resistance mechanisms
- metabolism
- altered ribosomes
- altered uptake
aminoglycoside resistance: the ___ rRNA binding site can be altered through point mutations, observed clinically with mycobacterium tuberculosis
a. 16S
b. 30S
c. 50S
d. 70S
a. 16S
which is TRUE about the toxicity of all aminoglycosides?
a. ototoxicity and nephrotoxicity are reversible
b. ototoxicity is reversible; nephrotoxicity is irrev
c. ototoxicity is irrev; nephrotoxicity is reversible
d. ototoxicity and nephrotoxicity are both reversible
c. ototoxicity is irrev; nephrotoxicity is reversible
T or F: serial audiograms are recommended with aminoglycosides
T
aminoglycosides concurrent use with _____ _____ or vanc can potentiate nephrotoxicity (answer is a drug class)
loop diuretics
respiratory paralysis from aminoglycosides can usually be reversed with _______ or calcium gluconate
a. probenecid
b. vancomycin
c. neostigmine
d. meclizine
c. neostigmine
aminoglycosides have broad spectrum activity, but in practice they are almost always reserved for gram _______
negative
how can penicillins and aminoglycosides be given together?
administered in different compartments (one in each arm) to avoid chemical rxn between the classes
penicillin/aminoglycoside combinations are used to treat
a. bacterial endocarditis
b. tuberculosis
c. UTIs, burns, some pneumonias, joint and bone infections
a. bacterial endocarditis
streptomycin is most often used to treat
a. bacterial endocarditis
b. tuberculosis
c. UTIs, burns, some pneumonias, joint and bone infections
b. tuberculosis
gentamicin use
a. bacterial endocarditis
b. tuberculosis
c. UTIs, burns, some pneumonias, joint and bone infections
c. UTIs, burns, some pneumonias, joint and bone infections
most important aminoglycoside
gentamicin
which aminoglycoside is used to treat nosocomial infections (hospital-acquired)?
a. tobramycin
b. plazomicin
c. amikacin
d. gentamicin
e. neomycin
f. streptomycin
c. amikacin
Amikacin A’s important moiety that inhibits bacterial metabolism by R-factors
a. L-arginine
b. syn-methoxyether
c. L-hydroxyaminobuterylamide
d. C-6 hydroxyl
L-hydroxyaminobuteryl amide
tobramycin is adenylated at ___ and acetylated at ___
C2; C3
_______ has superior activity vs. Pseudomonas aeruginosa than Amikacin, it is widely used parenterally to treat gentamicin-resistant Pseudomonas aeruginosa infections
tobramycin
2 orally used aminoglycosides
neomycin B
paromomycin
two aminoglycosides used clinically to suppress gut flora in travelers diarrhea and prophylactically prior to GI surgery to dec the incidence of peritonitis
neomycin and paromomycin
__________ is used to treat amoebic dysentery as well as dwarf tapeworm and beef tapeworm
a. paromomycin
b. gentamicin
c. streptomycin
d. erythromycin
a. paromomycin
first antibiotic used to cure tuberculosis
streptomycin
skipped plazomicin and streptomycin
ok
macrolides are usually ___-membered lactone rings
14
drugs ending in “mycin” comes from ?
a. streptomyces
b. micromonospora
a. streptomyces
drugs ending in “micin” comes from ?
a. streptomyces
b. micromonospora
b. micromonospora
which sugar of macrolides is most important for activity?
a. desosamine sugar
b. cladinose sugar
c. pentose sugar
a. desosamine sugar
(b. is less important, c. is not on the structure)
Macrolides are polyketides because they are produced by sequential addition of _______ groups to a growing chain. This results in _______ groups on alternate carbon atoms in the macrolide ring.
propionate
methyl
The pKa of the amine in erythromycin is ___. The amine can form salts that are more soluble
8.8
Macrolide binding mainly involves the bacterial ___ RNA and not the protein
23S (part of 50S)
4 resistance mechanisms for macrolides
- Lactone ester hydrolase induced to degrade the macrolides by hydrolysis of the macrocycle
- A2058 methylation
- Mutation of A to G in A2058
- An efflux pump ejects drugs from cell by an active transport process
Certain organisms like Pseudomonas spp. and Enterobacter spp. exhibit _______ _______ by not allowing entry of macrolide antibiotics
intrinsic resistance
erythromycin derivative that is stable in acid due to 6-OCH
clarithromycin
amine analog, acid stable, N-methylated methyleneamino moiety replaces C-9 ketone
a. erythromycin
b. clarithromycin
c. azithromycin
c. azithromycin
main route of erythromycin metabolism is _________ in the liver
demethylation
erythromycins are primarily used for infections of skin and soft tissues primarily caused by gram ______ bacteria
positive
clinical use of erythromycins look at that
okay
long term use (10-20) days of macrolides can induce a reversible _______ _______
a. pseudomembranous colitis
b. cholestatic hepatitis
c. aplastic anemia
d. tendon rupture
b. cholestatic hepatitis
how is clindamycin metabolized?
CYP P450
erythromycin can inc the probability of _______ _______
a. pseudomembranous colitis
b. cholestatic hepatitis
c. aplastic anemia
d. pyloric stenosis
d. pyloric stenosis
why is oral erythromycin given as enteric coated or as more stable salts or esters?
it is inactivated by gastric acids
