8a – Phenicols Flashcards
1
Q
What are the main phenicols in vet med?
A
- Florfenicol: has a fluorine
- Chloramphenicol: has a chlorine
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
3
Q
Nuflor indications in cattle and then swine
A
- Cattle: respiratory, foot rot, pinkeye
- Swine: respiratory
- *can not use IN LACTATING DAIRY COWS
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
5
Q
Aquaflor indications in salmon
A
- Aeromonas
- Vibrio infections
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
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
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
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
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
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.
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
13
Q
What is the bioavailability of florfenicol?
A
- Prolonged (but variable) absorption after IM/SC injection
- *flip-flop kinetics: LONG ACTING (1+ weeks)
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
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
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
