Exam 1 - Cushman (Lecture 3)

Question 1

aminoglycosides “core structures”

Answer 1

streptidine
2-deoxystreptidine

these link to aminoglycoside rings in aminoglycoside antibiotics

Question 2

aminoglycoside examples

Answer 2

tobramycin
plazomicin
amikacin A
gentamicin C2
neomycin B
streptomycin

Question 3

aminoglycoside MOA

Answer 3

Inhibit protein biosynthesis by binding the 30S ribosomal subunit (A site). Causes formation of nonsense proteins leading to leakage of ions and cell death.

Question 4

aminoglycoside uptake by bacteria

Answer 4

1. displacement of MG++ and Ca++ ions that form salt bridges
2. passage through the cytoplasmic membrane is an active transport process

Question 5

resistance mechanism by bacteria against aminoglycosides (list the 3)

Answer 5

1. bacterial metabolism
2. altered ribosomes
3. altered aminoglycoside uptake

Question 6

1. bacterial metabolism

Answer 6

Bacteria inactivate aminoglycosides through acetylation, adenylation and phosphorylation. These enzymes that do this show cross resistance to all aminoglycoside antibiotics

Question 7

2. altered ribosomes

Answer 7

at the 16S rRNA binding site

Question 8

3. altered aminoglycoside uptake

Answer 8

less common

Question 9

major tox. in aminoglycosides

Answer 9

ototoxicity (irreversible)
nephrotoxicity (reversible)

Question 10

DI in aminoglycosides

Answer 10

nephro: other nephrotoxic antimicrobials (vanco, amphotericin)
loop diuretics (ethacrynic acid and furosemide)

above should be avoided in combo with aminoglycosides

Question 11

reasons why aminoglycoside toxicity risk may be increased

Answer 11

elderly
treatment lasting more than 5 days
renal fxn impairment
high doses

Question 12

monitoring parameters of aminoglycosides

Answer 12

serum drug conc.
renal fxn (SCr)

Question 13

aminoglycosides are (broad/narrow) spectrum against gram (-/+)

Answer 13

broad, both gram (-) and (+)

Question 14

Aminoglycosides are usually used to treat gram (-/+), and usually used in combo with ______ antibiotics. These should be given one dose in each arm. Why?

Answer 14

gram (-), penicillin
-one in each arm to avoid inactivation of both drugs in a chemical reaction to each other

Question 15

penicillin/aminoglycoside combos are often used to treat _____ ________

Answer 15

bacterial endocarditis

Question 16

streptomycin is most often used to treat _______

Answer 16

tuberculosis

Question 17

gentamicin is used for ______, ______, _______, and _____/_____ infections caused by susceptible gram (-) infections

Answer 17

UTIs, burns, some pneumonias, and bone/joint infections

Question 18

which of the aminoglycosides has retained antibacterial activity against nosocomial (hospital acquired, resistant infections)?

Answer 18

amikacin

Question 19

amikacin is used for:
-3 bugs
-one extra use

Answer 19

-Mycobacterium tuberculosis, Francisella tularensis, sever Pseudamonas aeruginosa
-aminoglycoside-resistant nosocomial infections in hospitals

Question 20

tobramycin is used for:

Answer 20

Pseudomonas aeruginosa, usually those that are gentamicin resistant

Question 21

Why is gentamicin considered the best aminoglycoside?

Answer 21

-low cost
-reliable activity against all bu the most resistant gram (-) aerobes
-used to treat UTI, bone and joint infections caused by gram (-) bacteria

Question 22

orally used aminoglycosides

Answer 22

neomycin B
paromomycin

Question 23

streptomycin can be used against what 3 disease states

Answer 23

tuberculosis
bubonic plague
tularemia

Question 24

Plazomicin (Zemdri) uses and susceptible microorganisms

Answer 24

cUTI, including pyelonephritis
E. coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae

Question 25

Plazomicin tox.

Answer 25

nephro oto neuromuscular blockade teratogenicity

Question 26

macrolide antibiotics examples

Answer 26

erythromycin A clarithromycin azithromycin

Question 27

important structural piece for macrolide antibiotics

Answer 27

desosamine sugar

Question 28

macrolide MOA

Answer 28

inhibit bacterial protein synthesis by binding reversibly to the P site of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA from the A site to the P site.

Question 29

is macrolide bactericidal or bacteriostatic?

Answer 29

mostly bacteriostatic, but can be bactericidal at high concentrations

Question 30

1st resistance mechanism to macrolides

Answer 30

1. lactone ester hydrolase induced to degrade macrolides by hydrolysis of the macrocycle

Question 31

2nd resistance mechanism to macrolides

Answer 31

2. a specific adenine base (A2058) on the 23S RNA molecule of the 50S ribosomal subunit is methylated. This inhibits the binding of the macrolides to the 50S subunit.

Question 32

3rd resistance mechanism to macrolides

Answer 32

mutation of adenine to gaunine at the A2058 site results in 10,000 fold reduction in binding of erythromycin and clarithromycin to the 23S subunit.

Question 33

4th resistance mechanism to macrolides

Answer 33

efflux pump ejects drug from cell via active transport

Question 34

Why does clarithromycin have better stability in acid than erythromycin?

Answer 34

6-OCH3 derivative blocks ketal formation at low pH. enhances oral absorption

Question 35

Why is azithromycin acid stable?

Answer 35

Acid stable and reliable absorption due to N-methylated methyleneamino moiety replacing the C9 ketone, making ketal formation no longer possible.

Question 36

erythromycin is mainly metabolized in the ____

Answer 36

liver t1/2: 1.5 hr

Question 37

DI Macrolides can inhibit the metabolism of the following drugs:

Answer 37

carbamazepine cyclosporin disopyridine midazolam quinidine theophylline triazolam zidovudine

Question 38

DI Macrolides activity can be reduced with the metabolism of the following drugs:

Answer 38

rifampicin rifabutin

Question 39

DI Macrolides can cause serious consequences with the following drugs:

Answer 39

ergotamine digoxin methylprednisolone

Question 40

erythromycin clinical uses

Answer 40

skin and soft tissue infections caused by gram (+) bacteria

Question 41

All orally administered versions of erythromycin are given as _____ ______ or as more stable salts or esters

Answer 41

enteric coated