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
cotrimoxazole clearance
excreted in urine
what does cotrimoxazole contain?
sulfamethoxolate and trimethoprim
cotrimoxazole uses
UTRI
resp tract infection
MRS and comm acquried skin and soft tissue infection penumocystis pneumonia caused by PNEUMOCYSTIS JIROVECI
cotrimoxazole adverse
skin rxn eg. rash
photosen
nausea vomitting
megaloblastic anemia (folic acid ef)
drug for urinary antiseptic (1)
nitrofurantoin
nitrofurantoin use
lower UTI
nitrofurantoin MOA
reduce drug to hgihly active intermediate that inhibits enzymes and disrupts synthesis of proteins, DNA, RNA
nitrofurantoin spectrum
against e coli and enterococci
pos and neg
nitrofurantoin ROA
oral
nitrofurantoin absorption
rapidly from GIT
nitrofurantoin distri
high urinary conc while limiting sytemic exposure
- high conc in urine fast–> lower systemic exposure of drug
nitrofurantoin adverse
nausea, vomiting
leukpenia, hemolytic anemia
- hepatocellular damage
- pulmn toxicity for eledrly
nitrofurantoin CI
- imparied renal func
- pregnant
- infants <1 month
classes of polymyxins (2)
- polymyxin B
2. colistin
diff between polymyxin B and colistin
polymyxins B administered directly as active antibiotic vs colistin admin as inactive prodrug
polymyxins MOA
bactericidal
disrupt structure of cell membrane phospholipid and increase cell permeability
polymyxins spectrum of activity
NARROW spectrum, mainly gram NEG
used for multidrug resistant gram neg bac
not useful agaisnt atypical and gram POS
polymyxins ROA
iv, inhalation
polymyxins adverse
nephrotox
neurotox eg. confusion, hallucination
fosfomycin spectrum
against wide range of gram POS and NEG
fosfomycin MOA
interferes with cell wall synthesis
fosfomycin MOA
interferes with cell wall synthesis
advatnage / spectrum of fosfomycin
good against resistant bacteria
fosfomycin uses
UTI
fosfomycin ROA
rapid absorption with oral admin and is converted to fosfomycin
poor systemic absorption
adverse effects of fosfomycin
GI, headache, vaginitis
anti protozoal agents
protozoal infectiosn in underdev countires
unicellular eukaryotes- have met processes closer to those of human
how to treat amebiasis
chemotherapy
- luminal- act on parasite in lumen
- systemic- in intestinal wall and liver
- mixed amebicides
metronidazole MOA
serve as electron acceptor–> form cytotoxic free radicals that result in protein and DNA damage
metro stronger against ANAEROBES
metronidazole absorption
complteley and rapidly absorbed after ORAL adin
metronidazole distri
distri well into body and in CSF
metronidazole elim and met
heptaic met- accum in pt with severe hep disease
elim- in urine
metronidazole adverse
GI, unpleasant metallic tast
metronidazole pregnancy usage
cat B
avoid in first trimester
who not to give cirpofloxacin to
<18 yo– will hv joint problem
dont give for serious lower UTI, mostly for upper
what to give for nail infections?
give orally- need to be absorbed systemically and accum at keratin
give azoles
