Quinolones - Pharm Flashcards
what are the DNA gyrase inhibitors
quinolones
MOA of quinolones
inhibit topoisomerase II (AKA DNA gyrase) and topoisomerase IV
what does topoisomerase II/DNA gyrase do
relaxes the positive supercoils ahead of the replication fork by negative supercoiling DNA
by quinolones inhibiting topoisomerase IV, what is this doing?
interferes with the separation of replicated DNA into daughter cells
which drug is in the 1st group of the quinolones?
the 1st group is largely limited to what kind of bacteria??
gram negative, aerobic bacteria
nalidixic acid
not used anymore
what drugs (4) are in the 2nd group of the quinolones?
these are largely active against which bacteria?
aerobic gram negative - like the 1st group
levofloxacin
ciprofloxacin
norfloxacin
ofloxacin
which drug is the most active in the 2nd group of the quinolones
cipro
within the 2nd group, which drug is best for streptococcus pneumoniae?
levofloxacin - it’s sometimes in group 3 for respiratory!
can the 2nd group of quinolones cover gram positive bacteria?
gram positive coverage is limited
can cover MSSA, but NOT all MRSA
which group of quinolones is actually good for gram positive bacteria?
third group
name 3 drugs in the 3rd group of the quinolones
moxifloxacin
gatifloxacin
gemifloxacin
could also consider levofloxacin here - all good for resp infections
what is a newer quinolone
delafloxacin
which group of quinolones is mainly for respiratory infection
3
which group 3 quinolone has good activity for anaerobes
moxifloxacin
compare the activity of cipro vs group 3 for gram negative bacteria, like pseudomonas
group 3 is same or inferior to cipro for gram negative, including pseudomonas
which group of quinolones is active for atypical bacteria like mycobacteria and legionella, and for anaerobes
2
MAJOR resistance mechanism to quinolones
1 or more point mutations in quinolone binding region of the target enzyme (topo 2 or 4), or change in permeability of the organism
name 2 plasmid mediated mechanism of fluoroquinolone resistance
-Qnr proteins protect DNA gyrase (topoisomerase II) from the fluoroquinolones
-modifying cipro by aminoglycoside acetyltransferase
QNR = plasmid mediated quinolone resistance
fluoroquinolones generally have HIGH bioavailability with the exception of…..
norfloxacin
true or false
fluroquinolones have low tissue penetration
FALSE - high
this is partly why so toxic
fluoroquinolones undergo _________ excretion with the exception of ________
renal - adjust dose!!!
moxifloxacin
important consideration of something that can impair fluoroquinolone absorption
divalent and trivalent cations
therefore, have them 2 hours b4 or 4 hours after the fluoroquinolone
which fluoroquinolone is used with caution in HEPATIC failure
moxifloxacin
____________ is a drug of choice for the prophylaxis and treatment of anthrax
cipro
name the 4 respiratory fluoroquinolones
levofloxacin
gatifloxacin
gemifloxacin
moxifloxacin
used for upper and lower Resp tract infections
are fluoroquinolones effective against UTI
yes - including when cause by pseudomonas
true or false
fluoroquinolones can be used for bacterial diarrhea
true
name 4 bacteria that cause bacterial diarrhea that fluoroquinolones can treat
shigella
salmonella
toxigenic e. coli
campylobacter
can fluoroquinolones be used in skin and soft tissue infections
yes
do fluoroquinolones have pseudomonas aeruginosa coverage
YES
AE’s of fluoroquinolones
GI - NVD, anorexia, abdominal pain
CNS - headache, dizzy, drowsy, insomnia, seizure (rare)
derm - rash, itching, edema, hives
PHOTOTOXICITY - few hours after exposure
musculoskeletal
as mentioned, fluoroquinolones have musculoskeletal adverse effects.
thus, who are they used in caution/not used in
caution - children
avoided in pregnancy
true or false
quinolones are bactericidal
TRUE
bactericidal, conc dependent
nitrofurantoin is a urinary _____
antiseptic
is nitrofurantoin bactericidal or static
cidal
nitrofurantoin is used for treatment of……..
lower UTIs ONLY
simple and uncomplicated
does macrobid have systemic antibacterial action? explain
NO
it is metabolized and excreted so rapidly
explain the MOA of nitrofurantoin
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
agent of choice in uncomplicated lower UTI
nitrofurantoin
how does resistance to nitrofurantoin happen
RARE - but by mutations in the reductase that reduces nitrofurantoin into unstable metabolites
AE nitrofurantoin
*pulmonary toxicity
*hemolytic anemia in G6PDH deficiency – bc produces reactive species - have no NADPH to reduce
GI issues
neuropathy
long acting formulation of nitrofurantoin
how often is it taken?
macrobid
twice daily
What is usually at position 6 in fluoroquinolones
what is exception
FLUORINE
exception is nalidixic acid, which is H
in general, topo 2 and 4 are important for bacteria in….
replicating DNA
all fluoroquinolones have what common feature
activity against all gram NEGATIVE AEROBIC bacteria
true or false
all fluoroquinolones inhibit MRSA
false -
some active against MRSA, but not all
all active against MSSA
true or false
all fluoroquinolones inhibit DHFR
no
name 2 specific things that cannot be taken with fluoroquinolones
milk and antacids
bivalent and trivalent cations
impairs absorption
true or false
moxifloxacin is not renally eliminated
true - hepatic
if taking milk/antacids how long to wait before/after fluoroquinolones
2 hours before or 4 hours after
WHY is nitrofurantoin only for lower UTIs
gets matabolized and excreted so fast that no systemic antibacterial reaction achieved
WHY is resistance to nitrofurantoin rare
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
nitrofurantoin has ____- toxicity
pulmonary
