Lecture 3- quinolones, folic acid antagonists, urinary antiseptics Flashcards
fluoroquinolones MOA
target DNA gyrase, primarily in gram neg bac and topoisomerase IV in gram pos bac to inhibit DNA replication
- gyrase: intro negative supercoils into DNA to prevent excessive positive supercoiling
- topo: promote separation of cms DNA into daughter cells
types of dna gyrase/topo inhibitor- fluoroquinolones (3)
- ciprofloxacin
- levofloxacin
- moxi
fluoroquinolones ROA
oral, IV, ophthalmic
fluoroquinolones clearance
renal, dose adjust
CIPROfloxacin indications
- most active agaisnt gram neg strains and enteric coliforms eg. penicillin, cephalosporins
- for travellers diarrhea
- in skin, bone and joint infections
- against P. aeruginosa
- should be AVOIDED in MRSA infections
- UTI but not first line (lower UTI mostly)
levo and moxi coverage
- better covrage against gram POS org esp S. penumoniaea
- better cov against atypical pathogens eg. mycoplasm
- useful in resp infections
fluoroquinolones adverse effects
- GI eg. diarrhea, nausea
- C. diff colitis
- headache dizziness
- phototox
- tendinitis
- prolong QT interval
fluoroquinolones and tb
not as first line as they may mask sx of tb
fluoroquinolones CI
myasthenia gravis- may exacerbate muscle weakness
classes of folate syntehsis inhibitors (3)
- sulfonamides
- trimethoprim
- cotrimoxazole
sulfonamides MOA
competetive inhibitors of dihydropteroate synthase
bacteriostasis induced can be REVERsed by PABA
sulfonamides distri
bound to serum albumin
distri well throughout bodily fluids and penetrate well into CSF
sulfonamides elim
renal
sulfonamide clinical uses
combined with trimethoprim
sulfonamides adverse effects
- crystalluria (form acetylated product which is toxic and ppt at neutral or acidic pH)
- hypersen eg. rash
- hemolytic anemia
- kernicterus- CI in children (brain damage)
trimethoprim MOA
potent inhibitor of bacterial dihydrofolate reductase
trimethoprim resistance
in gram neg bacteria due to altered dihydrofolate reductase that has lower affinity for trimethoprim
efflux pumps
trimethoprim absorption
rapid absorption with ORAL admin
widely distri into body
godoCSF penetration
trimethoprim elim
renal, mostly unchanged
trimethoprim adverse efefct
FOLIC ACID deficiency
anemai, leukopenia
cotrimoxazole MOA
synergistic antimic activity with inhibitrion of two sequential steps
- sulfamethoxaxole inhibits incorporation of PABA into difolate acid
- trimeoprim prevents reduction of dihydrofolate to tetrathydrofoalte
cotrimoxazole ROA
oral commonly
IV also can
cotrimoxazole distribution
good CSF penetration, readiliy crosses BBB