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Pharmacology > Fluoroquinolones > Flashcards

Fluoroquinolones Flashcards

1
Q

Enrofloxacin (Baytril)

A

Used for treatment of infections associated with susceptible bacteria

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2
Q

Enrofloxacin (Baytril) formulations for small animals vs large animals

A

Small animals- 20mg/ml
-oral tablets for dogs/cats
-IM solution for dogs
-otic solution

Food animals- use Baytril 100mg/ml
-injectable (SC) solution in cattle and swine for respiratory disease claims

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3
Q

Danofloxacin

A

-injectable SC solution in cattle for respiratory disease

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4
Q

Marbofloxacin formulations

A

-oral tablets for use in dogs and cats (Zeniquin)

-otic solution (Aurizon)

-Injectable solution for BRD in cattle (Forcyl)

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5
Q

Pradofloxacin

A

-oral tablet (dog) and suspension (cat) = Veraflox
*used for skin infections and wounds

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6
Q

Ciprofloxacin

A

Human formulations
-oral tablets and solution for IV use

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7
Q

Fluoroquinolones mechanism of action

A

Inhibits bacteria DNA function

  1. DNA winding and unwinding requires topoisomerase enzymes such as DNA gyrase
  2. Fluoroquinolones bind to DNA-DNA gyrase complex and inhibits the resealing of cut DNA= destroyed
  3. Fluoroquinolones also inhibit topoisomerase IV preventing DNA supercoils relaxation
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8
Q

Fluoroquinolones timing and concentration

A

-long post-antibiotic effect
-good evidence of bactericidal effect
-concentration dependent

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9
Q

Cmax and AUC for Fluoroquinolones

A

Cmax: MIC >10

AUC: MIC >125

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10
Q

What do you get when Concentration dependent effects are used properly?

A
  1. Maximize efficacy
  2. Minimize AMR
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11
Q

Fluoroquinolones spectrum of acitivity

A

-gram + species

  • most gram - species
    >BRD and SRD pathogesn
    >enteric pathogens

-Pradofloxacin- some anaerobes

-Pseudomonas (esp. CIPRO)

-Some mycoplasma, chlamydia, Rickettsia

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12
Q

What do fluoroquinolones not work against?

A

-less effective against Strep and Enterococcus

-most anaerobes (except PRADOFLOXACIN)

**Resistance emerged for many isolates= historical MICs not always accurate

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13
Q

Chromosomal resistance of fluoroquinolones

A

Chromosomal resistance (not passed between species but emerge over time)
-single point mutations that over time eventually leads to enzymes that cannot be recognized by Fluoroquinolones

**occurs due to selective pressure

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14
Q

Plasmid-mediated resistance of fluoroquinolones

A

-qnr gene which protects DNA gyrase from fluoroquinolones binding

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15
Q

Cause of chromosomal mutation

A

Due to selective pressure
-Prolonged exposure (chronic low dose therapy) promotes this resistance

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16
Q

Dosing of fluoroquinolones

A

Should be used in high dose, short course therapy
-increase efficacy (concentration-dependent effect)
-minimize emergence of fluoroquinolone resistance

17
Q

Warning statements

A

-Baytril 100- not to be used as mass medication (because will lead to resistance).

*Says to be used after first choice treatment failed… but this is a BAD IDEA

-used with pathogen culture and drug susceptibility testing

-don’t used extra label manner in cattle, swine, and other species

18
Q

Fluoroquinolone absorption

A

-good oral bioavailability in most species
*cipro often lower than enro

19
Q

What decreases oral bioavailability of fluoroquinolone?

A

Chelation with divalent cations
*not an issue unless they are mixed with other substances

20
Q

Oral Fluoroquinolones

A

Mostly compatible in mixtures; generally stable
-not great with chelated cations (Al or Fe)… reduce stability in half

21
Q

Fluoroquinolones distribution

A

-lipophilic drug and low protein binding= high distribution to tissues
*tissue concentrations greater than plasma concentrations
*includes CSF and prostate

-taken up by phagocytic cells= antimicrobial activity persists, good for intracellular pathogens
*similar to macrolides

22
Q

Potential uses of fluoroquinolones in horses

A

-pleuropneumonia
-Pseudomonas ulcers
-septicemia/meningitis

23
Q

Fluoroquinolones elimination

A

-Hepatic metabolism
*enro metabolized to cipro in dogs, cats, horses

-Excretion: mostly renal (filtration and tubular secretion. Some biliary.
*no need to change if worried about kidney or hepatic disease

24
Q

Typical half life for fluoroquinolones

A

4-10hrs
-once daily dosing is sufficient

25
Q

Enrofloxacin in snakes

A

Have renal portal system- occurs in birds and reptiles. Will take drug to the kidney before systemic circulation… can be excreted before it makes it to circulation

-Safe in one species will not mean it is safe in another

26
Q

Streptococcal shock from fluoroquinolones (adverse event 1)

A
  1. Streptococcal shock syndrome and necrotizing fasciitis
    -strep canis infected by bacteriophage and allows for transfer of genetic material
  2. Treat with enrofloxacin
    -enro causes bacterial damage, causing upregulation of protein transcription to fix damaged DNA (SOS response)
  3. Results in Phage genes encoding a toxin which are upregulated= TOXIC SHOCK and NECROTIZING FASCIITIS
    *can be increased further by NSAID or steroid use
27
Q

Arthropathies (adverse event 2)

A

-Articular cartilage lesions occurs from chronic high dose FQ use
*in juvenile dogs and foals

-likely due to chelation of Mg2+

28
Q

Fluoroquinolones label information for arthropathies

A

Don’t use during rapid growth phase in dogs
-small/medium: 2-8mths
-Large: up to 1yr
-Giant: up to 18mths

29
Q

Drug interactions (adverse event 3)

A

-CYP enzyme inhibition (Enro/cipro)
-P-gp substrates

30
Q

Retinopathy in cats (adverse event 4)

A

-Feline ABCG2 transporter genes different than other species resulting in decreased transport
-results in accumulation of enro/cipro at retina= retinal degeneration or atrophy
*at supra-therapeutic doses

*does not occur with prado, and likely not with others

31
Q

Where are ABCG2 transporters located?

A

Retinal capillaries
-present in the blood-retinal barrier pumping drugs out

32
Q

Bone marrow suppression (adverse events 5)

A

USA: PRADO approved in cats, contraindicated in dogs

Canada: Prado tablets approved for dogs, suspension for cats

33
Q

Mild FQ events

A

-GI relatively mild irritation

-Neuro: seizures in dogs, cats, horses
*IV injection in horses= administer slow
*Baythrill- enro gives hallucinations in people

Pharmacology (41 decks)

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