Inhibitors of Nucleic Acid Function or Synthesis Flashcards
What do topoisomerases do?? how do they act?
Topoisomerase: A class ofenzymes that alter the supercoiling of double-stranded DNA. The topoisomerases act by transiently cutting one or both strands of the DNA.
name the four generations of fluoroquinolones
1st gen - nalidixic acid, neggram 2nd gen - ciprofloxacin (cipro), norfloxacin (noroxin), ofloxacin (floxin) 3rd gen - levofloxacin (levaquin) 4th gen - moxifloxacin (avelox)
what is the MOA if fluoroquinolones
they enter by passive diffusion through porins. inhibit replication of bacterial DNA by interferring with bacterial DNA gyrase (topoisomerase 2) during replication. they bind to both enzyme and DNA forming a complex leading to cell death by DNA cleavage.
fluoroquinolones are bacteriostatic. t/f?
false. they are bactericidal.
which gram - organims are fluoroquinolones effective against?
enterobacteria, moraxella cattrhalis, pseudomonas, legionella, haemophilus influenzae, chlamydia, mycobacteria
fluoroquinolones are effctive in ___________ but not __________.
gonorrhoea but not syphilis
which fluoroquinolones has activity against streptococcus pneumoniae
levofloxacin
which fluoroquinolone is used to reduce the incidence of post surgical UTI
levofloxacin
2nd gen fluoroquinolones are addtionally active against which atypical organisms?
chlamydia/mycoplasma pneumoniae
1st gen fluoroquinolones use is restricted to ttt of?
uncomplicated UTI
what are the therapeutic indications of ciprofloxacin
prophylaxis against G- in nuetropenic patients
w aminoglycosides for ttt of febrile neutropenia
meningitis prophylaxis and carrier (hajj season)
for multi drug resistant TB
name the most commonly used fluoroquinolone
ciprofloxacin
typical therapeutic applications of ciprofloxacin
respiratory infections, UTI, gastric infections, anthrax, gonorrhea
norfloxacin is used to treat?
complicated and uncomplicated UTI and prostatitis
is norfloxacin used to treat systemic infections. why?
No because it is only concentrated in the urine
uses of levofloxacin
prostatitis due to ecoli and STD
which STD is levofloxacin not effective against
syphilis
levofloxacin has excellent activity against
a. respiratory infections
b. syphilis
c. diarhhea
respiratory infections due to streptoccocus penumoniae
what are the reasons for resistance of fluoroquinolones
altered target : mutations in DNa gyrase and topoisomerase IV
decreased accumulation : decreased porins and decreased drug (efflux pump)
the absoprtion of fluoroquinolones is decreased by
antacids al3+ and mg2+
diet containing calcium and zinc
fluoroquinolones accumulate in __________ and __________.
macrophages and leukocytes.
the following is NOT an adverse reaction of fluoroquinolones
a. nephrotoxicity
b. phototoxicity
c. ototoxicty
d. CNS problems
c. ototoxicity
caution must be taken with fluoroquinolones in CNS problems such as __________.
epilepsy
name a drug that inteferes with th metabolism of fluoroquinolones
cimetidine
ciprofloxacin and ofloxacin inhibit the metabolism of which 2 drugs
theophylline and warfarin
Microorganisms commonly complicating UTI include:
E. coli (80% of cases)
Staphylococcus saprophyticus
Klebsiella pneumoniae
Proteus mirabilis
urinary tract antiseptics achieve concentrated levels in the systemic circulation. t/f
false. they concentrate only in the urine
in methenamine decomposition to __________ occurs at ____ pH.
formaldehyde, low pH
methenamine is used to treat _______ but not _______.
lower UTI but not upper UTI
methenamine is
a. bacteriostatic
b. bactericidal
a. bacteriostatic
how can the effect of methenamine be increased
Higher activity in acidic urine, ascorobic acid and cranberry can be given to lower urine pH
methenamine is contraindicated in
renal insufficiency
what is the MOA of nitrofurantoin
susceptible bacteria reduce it to an acive agent that inhibits enzymes and damages DNA
nitrofurantoin is
methenamine is
a. bacteriostatic
b. bactericidal
a. bacteriostatic
adverse effects of nitrofurantoin and methenamine
nitrofurantoin GI disturbances hemolytic anemia in G6PD neurological problems methenamine : albuminuria, hematuria, GI disturbances
