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PHARMACOLOGY 3 > 8a – Phenicols > Flashcards

8a – Phenicols Flashcards

1
Q

What are the main phenicols in vet med?

A
  • Florfenicol: has a fluorine
  • Chloramphenicol: has a chlorine
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2
Q

Florfenicol food animal products

A
  • Nuflor: injectable solution in cattle (IM/SC) and swine (IM)
  • Resflor: florfenicol + flunixin (NSAID) injectable solution (SC)
  • Zeleris: florfenicol + meloxicam (NSAID) injectable solution (SC)
  • Aquaflor: medicated premix for SALMON
  • *NOT FOR IV
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3
Q

Nuflor indications in cattle and then swine

A
  • Cattle: respiratory, foot rot, pinkeye
  • Swine: respiratory
  • *can not use IN LACTATING DAIRY COWS
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4
Q

Resflor and Zeleris indications in cattle

A
  • Respiratory disease
  • Pyrexia
  • *not necessarily helping them get over it more, but decent cost and make them feel better
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5
Q

Aquaflor indications in salmon

A
  • Aeromonas
  • Vibrio infections
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6
Q

Florfenicol small animal products

A
  • Osurnia, Claro
    o Ear medications with terbinafine (antifunal) and betamethasone or mometasone (steroid)
    o *’once per week’ ear med
    o Stays locally, not widely systemically absorbed
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7
Q

Chloramphenicol

A
  • ChlorPalm250, Chlor-palmitate (oral suspensions)
  • Label claim: various infections in dogs and cats
    o NOT a first line drug, but good for reserve
  • *human generic formulations widely used
    o Oral tablets and suspension
    o Injectable
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8
Q

What are the phenicols mechanism of action?

A
  • Binds to bacterial ribosomal 50S subunit (same as aminoglycosides)
    o Causes incorrect tRNA translation
    o **Disrupts bacterial protein synthesis
  • BUT inhibits mitochondrial protein synthesis in mammalian BONE MARROW
    o Impacts blood cell production
    o Dose-dependent effect
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9
Q

What are phenicols generally effective against?

A
  • Many gram +
    o *Including some MRSA/P
  • Many gram –
  • Many anaerobes
  • Some Mycoplasma: doesn’t really work
  • some Rickettsia and Chlamydia
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10
Q

What are phenicols generally NOT/LESS effective against?

A
  • Gram negative enterics resistant to chloramphenicol, less resistance to florfenicol
  • Pseudomonas
  • Enterococcus (hit or miss, at VMC=working well)
  • Rhodococcus
  • Mycobacterium
  • Nocardia
  • *resistance emerges rapidly in many bacterial species
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11
Q

How do organisms gain resistance to phenicols?

A
  • Enzymes adding acetyl group
    o Prevents binding to ribosome 50S subunit (chloramphenicol acetyltransferases, CAT)
    o **FLOR less vulnerable to acetylation
  • Decrease phenicol permeability
  • Increase efflux pumps (floR gene in Gram negative enterics)
  • Mutations to 50S binding sites (slow process)
  • *resistance genes are typically mobile: plasmids, transposons, etc.
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12
Q

What is the bioavailability of chloramphenicol?

A
  • Overall good
  • May be higher in cats in fed state?
  • Inactivated in rumen, but NOT a real-world issue
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13
Q

What is the bioavailability of florfenicol?

A
  • Prolonged (but variable) absorption after IM/SC injection
  • *flip-flop kinetics: LONG ACTING (1+ weeks)
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14
Q

Flip flop kinetics of florfenicol

A
  • IM: Flatter slope=slower rate of ELIMINATION
  • IV or IMM: same slope=same rate of elimination, no absorption occurring
  • *absorption still occurring during elimination phase
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15
Q

Distribution of phenicols

A
  • Moderate/high Vd (compared to beta-lactams and aminoglycosides)
  • More even distribution between plasma, ECF and tissues
    o Careful during pregnancy: crosses the placenta
  • *not necessarily better, but can help get some hard to reach infections
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16
Q

Elimination of phenicols

A
  • Hepatic metabolism and glucuronide conjugation (so out through kidneys)
    o POOR in cats: longer half-life and dosing interval
    o Much longer half-life in YOUNG animals
  • Primarily renal EXCRETION of inactive metabolites
  • *Don’t need to worry about kidney failure BUT do need to consider liver issues
17
Q

Phenicol: bacteriostatic?

A
  • VERY difficult to reach MBC=not SAFE
  • Considered ‘time-dependent
    o Recommended T>MIC for >50% of dosing interval
    o Dosing more frequently makes sense: 2-4x/day
18
Q

Phenicol may be antagonistic with other antibiotics: clinical relevance

A
  • Recommended to NOT administer with other antimicrobials
19
Q

Chloramphenicol and drug interactions

A
  • Hepatic metabolism interactions
    o Microsomal enzyme INHIBITOR (CYP)
    o Can prolong barbiturate anesthesia: NOT relevant now
    o Can inhibit metabolism of phenobarb and other CYP-mediated drugs
20
Q

Florfenicol and drug interactions

A
  • NOT KNOWN to cause hepatic drug interactions
    o Why? Food animals, no one actually goes looking for it.
21
Q

**What are the AE of phenicols?

A
  • Blood dyscrasias
  • GI AE
22
Q

**Blood dyscrasias

A
  • Types: Aplastic anemia, pancytopenia
    o Decreased production of RBC, WBC, platelets
  • Dose-dependent AND dose-INDEPENDENT
23
Q

*Dose-dependent blood dyscrasias due to phenicols

A
  • can be caused by chloramphenicol and florfenicol
    o Mitochondrial protein inhibition in BONE MARROW
    o Occurs in humans and animals
    o Related to total phenicol exposure (AUC)
  • *cats more likely to develop toxicity (due to increased exposure and decreased clearance)
24
Q

*Dose-independent blood dyscrasias due to phenicols

A
  • Idiosyncratic
  • Humans=can be fatal
    o 1 in 30,000
  • Very few reports in vet med
  • Related to para-nitro group on chloramphenicol
    o Does NOT occur with Florfenicol (lacks para-nitro group)
  • When give chloramphenicol to humans: give gloves
    o Won’t happen if NOT systemically absorbed
  • **chloramphenicol is BANNED FOR USE IN FOOD ANIMALS
25
Q

GI AE: chloramphenicol

A
  • Vomit
  • Diarrhea
  • Inappetence
26
Q

GI AE: florfenicol

A
  • Change in GI normal flora leads to diarrhea in claves
    o Enough drug distribution
27
Q

Chloramphenicol label dose

A
  • Dogs: lower dose, TID
  • Cats: higher dose, BID
  • *older sources recommend lower doses, but higher doses are more appropriate
  • *prolonged administration is NOT recommended
28
Q

Why is prolonged administration of Chloramphenicol NOT recommended?

A
  • **Due to AMR and/or AE
    o AMR happens quicker than other products (florfenicol is not as quick)
  • Limit to 10 days of therapy
  • If no clinical response in 3-5 days: discontinue treatment and reconsider diagnosis
29
Q

Florfenicol in cattle label indications for foot rot or pink eye

A
  • DO NOT use for foot rot or pink eye

PHARMACOLOGY 3 (15 decks)

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