Quinolones Lecture 25 Flashcards
Quinolones Structure and chemistry
strucually related to nalidixic acid
all agents besides nalidixic acid have been fluorinated, making these compounds less susceptible to resistance
Quinolones MoA
DNA gyrase is essential for supercoiling of cellular DNA by a nicking, pass thorugh, and resealing process
quinolones inhibit the enzymatic activity of bacterial DNA gyrase and promote the cleavage of DNA within the enzyme DNA complex
Bactericidal
Quinolones names and proerpties
ciprofloxacin: 3.2 Hour half life. 70% Bioavail. 29% renal excretion
oflaoxacin: 5 hour half life. 95% bio. 73 renal
levofloxacin: 6-7 hours half life. 100% bio. 61-86% renal
moxifloxacin: 9-16 hours. ~90% bioavialble. 15-21 renal excretion
gemifloxacin: 7 hour. ~70% bioavilablity. 36% renal
Quinolones absorption
food decreases rate, but not extent, of absorption
magnesium, aluminum, and/or calcium containing antacids ecrease the oral bioavailability
bioavailability varies with agents
Drug interactions quinolones
theophylline: decreased theophylline metabolism. Ciprofloxacin can double theophilline levels. Levofloxacin but no well documented effects.
antacids/iron/sucralfate: interfere with absorption of quinolones. Do not give within 2 hours of quinolone dose.
warfarin: increased anticoagulant effect possibly due to metabolism or protein binding changes. Levofloxacin: no well documeted effects, should monitor.
AE: Quinolones
Hypersensitivity: maculopapular rash, urticaria, pruritis, anaphylaxis/angioedema, photosensitivity.
gastrointestinal reactions: abnormal liver function tests. Dia/N/V
nephrotoxicity
CNS: HA/D
muscoloskeltal: arthropathy (not indicated for under 18 years of age; however debates occuring). Tendon rupture
SoA quinolones
G+: s. pneumonia, s. pyogenes, s. agalactiae, s. aureus, e. faecalis?
G-: salmonella, shigella, neisseria gon, H flu, M. cat, M. Morganii, proteus mirabilis/vulgaris, e coli, K. pneumonia, P. aeruginosa, enterbacter.
Summary or other quinolones
ciprofloxacin: excellent gram negative coverage
levofloxacin, gemifloxacin, moxifloxacin: gram + (staph and strep) and gram negative coverage.
Quinolones indications
UTI, Uncomplicated urethral or endocervical gonorrhea, chlamydia, mild to moderate lower respiratory tract infections caused by susceptible organisms. PID, prostatitis, gastroenteritis/infectious diarrhea,
Skin/ Skin structure infections caused by susceptible organisms (ciprofloxacin ofloxacin. Levofoxacin and gemifloxacin, and moxifloxacin better gram+ coverage, Moxifloxacin covers anaerobes well)
Bone and joint infections caused by susceptible organisms. (ciprofloxacin and ofloxacin)
complicated intra abdominal infections: cirpofloxaci/metronidazole or moxifloxacin
Quinolones: Ciprofloxacin
Widest range of FDA approved indications
cirploxacin is most potent of the quinolones against gram -. 4x more potent against pseudomonas
due to excellent biavailability oral form should be used in patients with functioning GI tracts or severely ill where absorption may be impaired
gram + activity very variable
Quinolones: Levofoxacin, gemifloxacin, moxifloxacin
gram + coverage, including resistant pneumoccous
g-: not as potent as ciprofloxacin
atypical respiratory pathogens: mycoplasma, legionella
due to excellent bioavailability oral form should be used in patients with functioning GI tracts or severely ILL where absorption my be impaired.
MOxifloxacin covers intrabdominal infections (anaerobes) but not UTI.
G+, G-, atypicals
tetracycline members:
doxycycline, minocycline, demecyocyline, oxytetracycline, chloratetracycline, tetracycline
Tetracycline: MoA
reversibly bins to 30s ribosomal subunit: decreases protein syntehsis
bacteriostatic
absorption decreased by food: variable from 20-50% for various TCN
characteristics of tetracyline. Bioavailbility
Bioavailability varies dependt on products.
doxy and mino: 90-100
tetracycline, demeclocyline, oxytetracycline: 58-75%
Tetracycline: elimination
renally: tetracycline, oxytetracycline, demeclocycline
hepatobiliary: doxycycline, minocycline
AE: tetracycline
photosensitivity
discoloration of developing teeth: bones and teeth developing during pregnancy and in children through 8 years old.
reversible diabetes insipidus associated with demeclocycline. Ue this side effect to treat SIADH
Vestibular AE with minocycline: dizziness, ataxia, vertigo.
fanconi like syndrome: N/V, lethargy, polydipsia, polyuria, proteinuria, acidosis, hypkalemia
associated with use of outdated citric acid formulation of tetracycline.
Tetracycline: drug interactions
decreased absorption of TCN agents when coadminister via chelation. Di and trivalent cations (Ca, Mg, Z, Al, Fe). Medications such as antacids. Diary prodcuts
potential antagonism effect since these agetns are static and many cidal agents require active growth
enhances anticoagulation of warfarin: increases PT/INR.
SoA Tetracycline
Broad spectrum coverage: G+, G-, Atypicals, Rickettsia
Clinical use: tetracycline
rickettsia infections (parasites): rocky mountain spotted fever
mycoplasma pneumonia
chlamydia infections: urogenital 7 days of doxy
acne
H. pylori in combination with other agents: bismuth, Metro, PPI. QID dosing: less patient compliance.
Clinical use for brucellosis: tetracycline
Brucellosis: unpasturized cheeses, milk.
humans become infected by coming in contact with animals or animal products that are contaminated with brucella.
In humans brucellosis can cause a range of symptoms that are similar to the flu and may include fever, sweats, headaches, back pains, and physical weakness.
Severe infections of the CNS or lining of the heart may occur.
Brucellosis can also cause long lasting or chronic symptoms that include recurrent fevers, joint pain, and fatigue.
Clinical use for vibrio cholera/vulnificus: tetracyline
V. Vibrio is an acute diarrheal disease endemic in india and southeast asia whose causative agent is vibrio cholerae.
this condition can lead to severe dehydrtion in a matter of hours unless quickly treated
v. vulnificus can cause disease in those who eat contaminated seafood or have an open wound that is exposed to seawater.
Clinical use for borrelia burgdorferi: tetracyline
Lyme disease
lyme disease is a bacterial disease caused by borrelia brugdorferi.
within 1 to 2 weeks of being infected, people may have a bull’s eye rash with fever, HA, and muscle or joint pain.
SXS: some people have lyme disease and do not have any early symptoms while others have a fever and other flu like symptoms without a rash
after several days or weeks, the bacteria may spread throughout the body of an infected person. These people can get symptoms such as rashes in other parts of the body, pain that seems to move from joint to joint, and signs of inflammation of the heart or nerves
if the disease is not treated, a few patients can get additional symptoms, such as swelling and pain in major joints or mental changes, months after getting infected.
Tetracycline others
SIADH. Demeclocycline only!!!
Tetracycline summary
do not use in pregnancy/kids under 8
photosensitivity
fanconi like syndrome: outdated tetracycline
divalent and trivalent cations will chelate antibiotic
treatment of SIADH: demeclocycline
