Fluoroquinolones Flashcards
Amphoretic and zwitter ionic nature enable the drugs to act
as acids/bases and neutral
are we using 1st generation drugs?
no
2nd generation drugs
- Ciprofloxacin
- Enrofloxacin
- Marbofloxacin
- Danofloxacin
- Difloxacin
3rd generation drugs
Orbifloxacin
4th generation drugs used?
not really. at least not for this course.
static or cidal?
CIDAL
How does it go about inhibiting DNA synthesis?
Inhibits bacterial DNA gyrase / Type II topoisomerase
Which enzyme is Responsible for maintaining bacterial dna in the chromosome?
DNA gyrase / Type II topoisomerase in GRAM - bacteria!
What do the drugs target?
DNA gyrase enz
What do the drugs do to the DNA G enzyme?
prevents it from doing negative supercoiling so now the DNA strand has a whole bunch of positive supercoiling and the replication can’t be completed. dead bacteria.
So, Gram- have the Type II topoisomerase enzyme that these drugs can target.
What about Gram + bacteria?
Gram + have Type IV topoisomerase enzyme and if the drugs can target that one as well, BAM. broad spectrum baby.
Spectrum aka What can these drugs kill?
mostly G-.
Can kill PA with combo or CIPRO and MARBO!
Can do some G +
Intracellular
Rickettsia
Mycoplasma
CIPRO and MARBO together treats
PA
ENRO and MARBO together treats
Canine pyoderma Rickettsial infections Acute Ehrlichiosis in dogs Bartonella infections in cats Mycoplasma and Mycobacteria infections
PREMA treats
PRADO treats
MRSA and enterococci resistant to Vancomycin
Gram- and Gram+ enzymes/ocular lesions/uti/soft tissue
Factors that affect the fluoroquinolone action
1) Cations at the site of infection…Just like Aminos!
2) acidic pH
ORAL absorption…what’s the deal?
it’s pretty good.
not affected by food.
100% in small animals but low in ruminants. variable in horses.
ENRO and SARA treat
poultry infections
Distribution where and what are the exceptions?
really good and can get tissue concentrations comparable to that in the plasma EXCEPT EYE AND CNS
Enro has great concentration in
bone prostate skin
Enro, Marbo, Orbi= EMO
great for?
Prostate tissue.
Your prostate is sick and looks so EMO. So depressed man…
Why’s this group of drugs so good with treating intracellular pathogens?
Because they accumulate really well in phagocytic cells (Macs and neu’s)
Drugs are metabolized where?
liver via oxidation
3 MAIN ACTIVE METABOLITES!
DIFLO->SARAFLO
ENRO->CIPRO
PEFLO->NORFLOXACIN hey!
Enterohepatic circulation?
yep
Excretion happens where?
kidneys: glom and tubular secretion
bile
there’s an exception….
Where does DIFLO get excreted?
POOP! just like Doxy.
“Basic” Adverse effects
Photosensitivity like doxy
crystalluria
CNS effects
Unique Adverse effects
ARTHROPATHY UNIQUE. SEEN IN YOUNG ANIMALS. LAMENESS AND JOINT SWELLING SEEN WITH ENRO/MARBO/ORBI…REVERSIBLE
OCULAR TOXICITY IS UNIQUE AS WELL. Can end up in blindness.
Cataracts with ENRO
Issues with tendons as well. Tendinopathy.
CNS Excitation just like in horses with PENICILLIN
How does the joint arthopathy come about?
chelation of Mg2+ from the membrane= proteoglycan loss in articular cartilage
How can resistance come about?
can have mutations in that A gene for the DNA gyrase enzyme that would then allow structural modification.
can also decrease the amount of concentration intracellularly by reducing the number of porins on the target cells
Efflux
Type 1 2 or 3?
TYPE 1
