Flashcards in Fluoroquinolones & Drugs for UTIs Deck (53):
stats about UTIs?
- 15% prescribed antibiotics in US
- $1 billion spent on treating UTIs
- account for 7 million office visits, a million ER visits, 100,000 hospitalizations per year
UTI common pathogens?
- Escherichia coli = causes most community acquired infections (70-80%)
- Staphylococcus saprophyticus, G+ organism = causes 10-15%
- catheter associated UTIs caused by G- bacteria - proteus, klebsiella, seratia, pseudomonas
how do cranberries help w/ UTIs?
prevent flagella from forming in bacteria, help eliminate colonization
kidneys & UTI?
can become infected by urine back flow or blockage
ureters & UTI?
can carry bacteria between kidneys and bladder
bladder & UTI?
can become infected when urine collected there doesn't empty completely
rectum & UTI?
normally has bacteria in it
urethra in women & UTI?
in women is short and near vagina, makes it easy for bacteria to enter urinary tract
vagina & UTI?
allows entry for bacteria from rectum or from outside body, bacteria may then enter urethra
prostate & UTI?
surrounds part of urethra, may enlarge w/ age and block urine flow, can cause infection
urethra in men & UTI?
longer in men, harder for bacteria to reach inner structure
penis & UTI?
comes in contact w/ bacteria that can travel up urethra
pharmacodynamics of fluoroquinolones?
target DNA, DNA replication (DNA gyrase)
which fluoroquinolone is the DOC for UTIs?
what is CIPROFLOXACIN (cipro) used for?
- systemic infections
- anthrax prophylaxis
- P. AERUGINOSA
what is NORFLOXACIN (noroxin) used for?
what is OFLOXACIN (floxin) used for?
- STDs, not syphilis
- some systemic
what is LOMEFLOXACIN (maxaquin) used for?
what is LEVOFLOXACIN (levaquin) used for?
- community acquired pneumonia (CAP)
what is MOXIFLOXACIN (avelox) used for?
- active against penicillin resistant S. pneumonia
what is GATIFLOXACIN (tequin) used for?
- ocular application only
what is GEMIFLOXACIN (factive) used for?
- active against penicillin resistant S. pneumoniae
formula for fluoroquinolones?
medically important ones are synthetically fluorinated analogs of naladixic acid
mechanism of fluoriquinolones
- inhibition of DNA GYRASE prevents relaxation of positively supercoiled DNA that is required for normal transcription and replication (unwinds, replication, rewinds)
- inhibition of TOPO IV interferes w/ separation of replicated chromosomes to daughter cells
spectrum of fluoroquinolones
- primarily effective against aerobic G- rods (incl Enterobacteriaeceae, Citrobacter, Serratia, Neisseria)
- good G+ coverage (incl MRSA & pen resistant S. Pneum -- moxi- & gemifloxacin)
- antipseudomonal - CIPRO
- effective prophylactic against anthrax - CIPRO = DOC
- NOT EFFECTIVE against infections (except trove-, maxi-, gemifloxacin)
pharmacokinetics of fluoroquinolones
- well absorbed ORALLY - iron, Mg, Ca decrease absorption
- widely distributed, excellent tissue penetration (prostatitis - norflox/oflox)
- poor CNS penetration (newer ones better)
- most excreted through kidney, can be blocked by probenecid
resistance of fluoroquinolones
- change in gyrase enzyme (mutation)
- decreased permeability of bacteria
- antibiotic modification (ciprofloxacin)
adverse effects of fluoroquinolones
- GI DISTURBANCES (nausea, vomiting, diarrhea)
- headache, restlessness, dizziness, tremors
- skin rxn (rash, pruritis)
- all quinolones increase QT interval
- transient elevations of serum transaminase, LDH, alkaline phosphatases, etc
- CARTILAGE EROSIONS in animals (not to be used in children!)
- TENDON RUPTURE
contraindications of fluoroquinolones
- pregnant women
- children (cartilage damage < 18 yrs)
- cephalosporin (3rd gen)
DOC brucella species?
doxycycline + rifampin or aminoglycoside
DOC helicobacter pylori?
bismuth + metronidazole + tetracycline or amoxicillin
DOC pseudomonas aeruginosa?
antipseudomonal penicillin + aminoglycoside
DOC stenotrophomonas maltophilia?
DOC legionella species?
azithromycin + rifampin
quinolone + rifampin
characteristics METRONIDAZOLE (MOA)
- prodrug - nonenzymatically reduced by reacting w/ reduced ferredoxin (only found in anaerobes)
- metronidazole metabolites are taken up into BACTERIAL DNA and form unstable molecules - BACTERICIDAL
spectrum of metronidazole
- potent antibacterial activity against ANAEROBES
- G- and G+ bacilli (anaerobes)
- indicated for treatment of anaerobic or mixed intra-abdominal infections, vaginitis (bacterial), RTI, pseudomembranous colitis, endocarditis, acute gingivitis, dental infection
- helicobacter pylori eradication therapy as part of multi drug regimen
pharmacokinetics of metronidazole
- oral, IV, topical
- liver metabolism
- eliminated in urine
adverse rxns of metronidazole
- GI disturbances
- central and peripheral nervous system toxicity - convulsive seizures and peripheral neuropathy (w/ prolonged use) are serious adverse effects (rare)
- candida superinfection
exclusive UTI drugs?
- naladixic acid
properties of exclusive UTI drugs?
- renally excreted
- achieve HIGH URINARY CONCENTRATIONS - do not achieve therapeutic concentrations anywhere else in body
- bactericidal activity in urine
characteristics of NITROFURATOIN (furadantin)
- DAMAGES BACTERIAL DNA (prodrug)
- reduced in bacterial cells to highly reactive intermediate that can attack ribosomal proteins, DNA, metabolism, macromolecules
- wide spectrum of antibacteriostatic & bactericidal activity against G- and G+ bacteria (E coli, S pyogenes, citrobacter, klebsiella, enterobacter, salmonella, shigella, serratia, indole positive proteus)
- most proteus and pseudomonas = resistant
- treatment of uncomplicated UTIs - alternative for treatment of E coli resistant to trimethoprim-sulfamethoxazole & fluoroquinolones
absorption/activity of nitrofuratoin?
- rapid/complete absorption after ORAL use
- acidic urine increases therapeutic action (pH < 5.5)
- drug activity decreased when glomerular filtration impaired
- SHOULD NOT BE USED IF CREATININE CLEARANCE < 50 mL/min - w/ renal failure antibiotic does not reach sufficient levels in urine for antibacterial activity
- colors urine brown
toxicity of nitrofuratoin
- nausea, vomiting, diarrhea common (less GI upset if taken w/ food)
- allergic rxns - chills, fever, leukopenia, granulocytopenia, cholestatic jaundice, HEPATOCELLULAR DAMAGE, HEMOLYTIC ANEMIA (in G6PD deficiency)
- INTERSTITIAL PULMONARY FIBROSIS (in chronic usage, esp in elderly)
- neuro disorders - severe polyneuropathies & demyelination/degeneration of neurons
contraindications of nitrofuratoin
- pregnancy(38-42 wks gestation)
- less than one month age
- impaired renal function
characteristics of METHENAMINE
- ORAL (prodrug) - decomposes to FORMALDEHYDE & AMMONIA in the acid medium of urinary tract
- acidic urine increases therapeutic action
- well absorbed orally, but 10-30% occurs in stomach
- methenamine active against G- organism, esp E. Coli
- bacterial resistance to formaldehyde does not develop
spectrum of methenamine
- almost all bacteria are sensitive - those that increase pH of urine inhibit release of formaldehyde (proteus), combine w/ weak organic acid (hippuric acid)
toxicity of methenamine
- essentially non toxic bc little decomposition takes place in body until appearing in urine
- GI distress, occasionally allergic rxns
contraindications of methenamine
- hepatic insufficiency - conversion to formaldehyde releases ammonia
- renal insufficiency - crystalluria (low urinary output)
characteristics of NALIDIXIC ACID
- INHIBITS DNA SYNTHESIS of susceptible G- organisms
- not for systemic antibacterial use
- well absorbed ORALLY - iron, Mg, calcium lowers absorption