Quinolones - Pharm

Question 1

what are the DNA gyrase inhibitors

Answer 1

quinolones

Question 2

MOA of quinolones

Answer 2

inhibit topoisomerase II (AKA DNA gyrase) and topoisomerase IV

Question 3

what does topoisomerase II/DNA gyrase do

Answer 3

relaxes the positive supercoils ahead of the replication fork by negative supercoiling DNA

Question 4

by quinolones inhibiting topoisomerase IV, what is this doing?

Answer 4

interferes with the separation of replicated DNA into daughter cells

Question 5

which drug is in the 1st group of the quinolones?

the 1st group is largely limited to what kind of bacteria??

Answer 5

gram negative, aerobic bacteria

nalidixic acid

not used anymore

Question 6

what drugs (4) are in the 2nd group of the quinolones?

these are largely active against which bacteria?

Answer 6

aerobic gram negative - like the 1st group

levofloxacin
ciprofloxacin
norfloxacin
ofloxacin

Question 7

which drug is the most active in the 2nd group of the quinolones

Answer 7

cipro

Question 8

within the 2nd group, which drug is best for streptococcus pneumoniae?

Answer 8

levofloxacin - it’s sometimes in group 3 for respiratory!

Question 9

can the 2nd group of quinolones cover gram positive bacteria?

Answer 9

gram positive coverage is limited

can cover MSSA, but NOT all MRSA

Question 10

which group of quinolones is actually good for gram positive bacteria?

Answer 10

third group

Question 11

name 3 drugs in the 3rd group of the quinolones

Answer 11

moxifloxacin
gatifloxacin
gemifloxacin

could also consider levofloxacin here - all good for resp infections

Question 12

what is a newer quinolone

Answer 12

delafloxacin

Question 13

which group of quinolones is mainly for respiratory infection

Answer 13

3

Question 14

which group 3 quinolone has good activity for anaerobes

Answer 14

moxifloxacin

Question 15

compare the activity of cipro vs group 3 for gram negative bacteria, like pseudomonas

Answer 15

group 3 is same or inferior to cipro for gram negative, including pseudomonas

Question 16

which group of quinolones is active for atypical bacteria like mycobacteria and legionella, and for anaerobes

Answer 16

2

Question 17

MAJOR resistance mechanism to quinolones

Answer 17

1 or more point mutations in quinolone binding region of the target enzyme (topo 2 or 4), or change in permeability of the organism

Question 18

name 2 plasmid mediated mechanism of fluoroquinolone resistance

Answer 18

-Qnr proteins protect DNA gyrase (topoisomerase II) from the fluoroquinolones

-modifying cipro by aminoglycoside acetyltransferase

QNR = plasmid mediated quinolone resistance

Question 19

fluoroquinolones generally have HIGH bioavailability with the exception of…..

Answer 19

norfloxacin

Question 20

true or false

fluroquinolones have low tissue penetration

Answer 20

FALSE - high

this is partly why so toxic

Question 21

fluoroquinolones undergo _________ excretion with the exception of ________

Answer 21

renal - adjust dose!!!

moxifloxacin

Question 22

important consideration of something that can impair fluoroquinolone absorption

Answer 22

divalent and trivalent cations

therefore, have them 2 hours b4 or 4 hours after the fluoroquinolone

Question 23

which fluoroquinolone is used with caution in HEPATIC failure

Answer 23

moxifloxacin

Question 24

____________ is a drug of choice for the prophylaxis and treatment of anthrax

Answer 24

cipro

Question 25

name the 4 respiratory fluoroquinolones

Answer 25

levofloxacin gatifloxacin gemifloxacin moxifloxacin used for upper and lower Resp tract infections

Question 26

are fluoroquinolones effective against UTI

Answer 26

yes - including when cause by pseudomonas

Question 27

true or false fluoroquinolones can be used for bacterial diarrhea

Answer 27

true

Question 28

name 4 bacteria that cause bacterial diarrhea that fluoroquinolones can treat

Answer 28

shigella salmonella toxigenic e. coli campylobacter

Question 29

can fluoroquinolones be used in skin and soft tissue infections

Answer 29

yes

Question 30

do fluoroquinolones have pseudomonas aeruginosa coverage

Answer 30

YES

Question 31

AE's of fluoroquinolones

Answer 31

GI - NVD, anorexia, abdominal pain CNS - headache, dizzy, drowsy, insomnia, seizure (rare) derm - rash, itching, edema, hives PHOTOTOXICITY - few hours after exposure musculoskeletal

Question 32

as mentioned, fluoroquinolones have musculoskeletal adverse effects. thus, who are they used in caution/not used in

Answer 32

caution - children avoided in pregnancy

Question 33

true or false quinolones are bactericidal

Answer 33

TRUE bactericidal, conc dependent

Question 34

nitrofurantoin is a urinary _____

Answer 34

antiseptic

Question 35

is nitrofurantoin bactericidal or static

Answer 35

cidal

Question 36

nitrofurantoin is used for treatment of........

Answer 36

lower UTIs ONLY simple and uncomplicated

Question 37

does macrobid have systemic antibacterial action? explain

Answer 37

NO it is metabolized and excreted so rapidly

Question 38

explain the MOA of nitrofurantoin

Answer 38

activated inside bacteria by reduction of nitro via reduction by FLAVOPROTEIN NITROFURANTOIN REDUCTASE into unstable metabolites (radicals) these unstable metabolites disrupt the ribosomal RNA, DNA, and other intracellular components of bacteria

Question 39

agent of choice in uncomplicated lower UTI

Answer 39

nitrofurantoin

Question 40

how does resistance to nitrofurantoin happen

Answer 40

RARE - but by mutations in the reductase that reduces nitrofurantoin into unstable metabolites

Question 41

AE nitrofurantoin

Answer 41

*pulmonary toxicity *hemolytic anemia in G6PDH deficiency -- bc produces reactive species - have no NADPH to reduce GI issues neuropathy

Question 42

long acting formulation of nitrofurantoin how often is it taken?

Answer 42

macrobid twice daily

Question 43

What is usually at position 6 in fluoroquinolones what is exception

Answer 43

FLUORINE exception is nalidixic acid, which is H

Question 44

in general, topo 2 and 4 are important for bacteria in....

Answer 44

replicating DNA

Question 45

all fluoroquinolones have what common feature

Answer 45

activity against all gram NEGATIVE AEROBIC bacteria

Question 46

true or false all fluoroquinolones inhibit MRSA

Answer 46

false - some active against MRSA, but not all all active against MSSA

Question 47

true or false all fluoroquinolones inhibit DHFR

Answer 47

no

Question 48

name 2 specific things that cannot be taken with fluoroquinolones

Answer 48

milk and antacids bivalent and trivalent cations impairs absorption

Question 49

true or false moxifloxacin is not renally eliminated

Answer 49

true - hepatic

Question 50

if taking milk/antacids how long to wait before/after fluoroquinolones

Answer 50

2 hours before or 4 hours after

Question 51

WHY is nitrofurantoin only for lower UTIs

Answer 51

gets matabolized and excreted so fast that no systemic antibacterial reaction achieved

Question 52

WHY is resistance to nitrofurantoin rare

Answer 52

major resistance mechanism in general is changing the target site. however, the reactive species can target anything - RNA, DNA, and other component s---- resistance is rare

Question 53

nitrofurantoin has ____- toxicity

Answer 53

pulmonary