Fluroquinolones Flashcards
What are the 6 commonly used FQs and their formulations?
Enrofloxacin (Baytril) - small animal - IM solution for dogs - otic solution Baytril 100 - food animal - SC, solution in cattle and swine - resp disease - uncomplicated resp disease (better use macrolides, these are important for human medicine)
Danofloxacin (A180) “zoetis version of baytril100”
- SC and solution for cattle
- resp disease claims
Marbofloxacin (zeniquin)
- oral tablets (dogs/cats)
- otic solution
Orbifloxacin (orbax)
- oral tablets (dogs/cats)
Pradofloxacin (Verflox)
- oral tablets (dog), suspension (cats)
What is the human (many generics) FQ that is also a metabolite of enrofloxacin?
Ciprofloxacin
What is the MOA of FQs?
bacterial DNA inhibition
- toopisomerase 2 (DNA gyrase) binds to dsDNA and supercoils it - cuts and reconnects it (tightly wound DNA is needed for bacteria)
- FQ binds to DNA gyrase (inhibiting reconnection and destroys it)
- FQ also inhibits topoisomerase 4 (relaxes super coils)
What is the PK-PD relationship of FQ?
bactericidal concentration dependent
to maximize efficacy
- need an AUC/MIC ratio above 125 can can reach quickly with higher ratio
Why is it beneficial to hit em hard and fast with FQs (same as AGs)?
to reach concentration dependent doses
to minimize AMR (chromosomal mutations from pressure) from long term therapy
What is the spectrum of activity of FQs?
effective
- some gram + (staph), most gram - (BRD,SRD, enteric pathogens), some anaerobes (PRADO), Pseudomonas (CIPRO), some mycoplasma, chlamydia, rickettsia
less/not effective?
- strep and enterococcus (less), anaerobes (except PRADO)
What is FQ the best option for treating?
enteric pathogens
pseudomonas
What are the mechanism of resistance used for FQs?
lots of resistance emerged (historical MIC no accurate)
chromosomal mechanism (not transferred)
- mutations in topoisomerase genes
- decrease permeability/efflux
plasmid mediated
- qnr gene: protects DNA gyrase
cross resistance
chromosomal mutations occur with selective pressure
- chronic low dose
What bacteria is there lots of resistance in and what is emerging?
staph and pseudomonas (lots)
Mannheimia (rising)
What are FQ warning statements about resistance?
dont use in feedlot - mass medication
use susceptibility test
dont use extra label (illegal in US)
What is the PK of absorption with FQs?
good oral F
chelation with divalent cation = decrease F
is compounded FQ effective?
oral
- generally yes (stable)
- use flavouring agents
exception = chelation
enrofloxacin chelated
orbifloxacin chelated
- greatly reduces F
What is the PK of distribution?
lipophilic and low protein binding = high distribution to tissues
- tissue greater than plasma (but comparable)
- prostate and CSF as well
uptake into phagocytic cells
- antimicrobial activity persists (good for intracellular pathogens
What is the PK of elimination for FQs?
hepatic metabolism
- ENRO metabolized to CIPRO in dogs, cats, horses
- comparable activity
excreted
- renal (filtration and tubular secretion)
- some biliary
T1/2 between 4-10h
- SID
Will FQ be a good antibiotic to treat pleuropneumonia in horses?
no due to its ineffectiveness to treat streptococcus and anaerobes
- exception PRADO
use in combo
What is the mechanism behind streptococcal shock syndrome and necrotising fasciitis (an AE of FQ)?
strep canis infected with bacteriophage (transfer of genetic material)
- enrofloxacin causes bacteriophage damage (SOS response in gene transfer)
- encode toxin = shock
- exacerbated by concurrent NSAID or steroid use
what should you treat strep canis with instead of FQ and why?
streptococcal shock syndrome
treat with B-lactam
What other AE can occur with FQ?
Arthropathies
- chronic high dose can cause articular cartilage lesions (juv dogs, large breed, foals)
- due to chelation of Mg
Retinopathy in cats
- feline ABCG2 transporter gene (blood retina barrier to pump drugs away)
- accumulation of NEOR/CIPRO at retina = degen or atrophy
- high doses
- not with PRADO less with MARBO/ORBI
Bone marrow suppression
- in dogs with extremem doses
GI
- mild irritation
Neuro
- seizures in dogs, cats, horses
- IV injection slow in horses
- Baytril = enro hullucinations in people
What do FQ label claim about administration during growth periods?
dont use during rapid growth phase in dogs
- can be up to 18m in giant breeds
- 2-8m in small
What drug interactions should be considered with FQ?
CYP enzyme inhibtion (ENRO/CIPRO)
- pgyp substrates
enrofloxacin + theophyline = increase theophyline concentrations
