Tetracyclines Flashcards
What are the 4 different tetracycline drugs?
tetracycline (TC)
- food animals horses
- oral: water soluble and boluses
Oxytetracyclines (OTC)
- food animal only
- oral: premix and water soluble
- injectable (short acting IM/IV, long acting IM/SC)
TC & OTC human capsules used in small animal
Chlortetracycline
- oral mixes and boluses for food animal
Doxycycline
- small animal and horses
- oral: human tablet/capsule (may need to compound)
- no vet formulations
Why are tetracyclines irritating on injection?
likely due to carriers in formulation
- biomycin a little less irritating
What is the MOA of tetracyclines?
bind to 30s subunit - incorrect tRNA translation - disrupts bacterial protein synthesis requires energy dependent transport into bacterial cell to reach binding sites - animals lack tetracycline transport
What is the PK-PD relationship of tetracyclines?
bacteriostatic but can be cidal at high concentrations
time dependent
- prolonged exposure
TC,OTC and CTC broadly similar PD
- differences in clinical efficacy due to PK difference
- doxyclycline most permeability and activity
What is the spectrum of activity of tetracyclines?
effective
- some gram + and -, many anaerobes, some mycoplasma, some rickettsia, chlamydia, protozoa and spirochetes
less/not effective
- often staph resistant, gram - enterics, pseudomonas, enterococcus
is their resistance emergence?
emerges rapidly often alot of variance
- has been used for growth promotion
- if used for prevention must be used in max potential (feed)
What is the mechanism of tetracycline resistance?
plasma mediated tet gene (limits clinical usefulness)
failure in active transport of drug into bacteria
increased efflux
production of proteins that protect ribsome
What is the PK of absorption of tetracyclines?
oral F CTC/OTC poor doxycycline: much higher injectable OTC - high
What is unique about injectable OTC and PK?
high F
LA formulation = flip flop kinetics
- elimination much slower in IM or IV
IM still absorbed as eliminated
Shown in pig study, how does the bioavailability change fed or fasted?
much higher in fasted state
tetracyclines are ineffective againist enteric pathogens (wont absorb anyway)
What is the PK distribution of tetracyclines
good in most tissues and fluids
- CSF not good (pgyp)
low to moderate protein binding
except DXC
What is unique about TC distribution?
TCs bind to Ca/Mg
deposition in bones and teeth
What is the PK elimination of tetracyclines?
very little metabolism
some TC excreted in bile, intestine (pgyp)
enterohepatic recirculation
unchanged drug excreted via glomerular filtration
What is significant about unchanged drug being excreted in the kidney? what is the exception
high concentrations in urine
- used for UTI
- longer T-1/2 with renal failure
doxy excreted in feces
What is the T1/2 orally and with LA injectable?
6-8h
24h
what are the adverse effects of tetracyclines? (generally safe, but)
nephrotoxicity possible
- at very high dose with dehydration
CV collapse with rapid IV
- propylene glycol carriers in formation likely cause
chelation by Ca and heavy metals
- dont administer with dairy or antacid (lower F)
- young animals cause teeth staining (nbd)
What are the significant adverse MSK effects that can occur with OTC? what is the mechanism?
relax flexor tendons
Mechanism: inhibition of matrix metalloproteinase enzymes
What tetracycline can be used to treat contracted tendons in neonatal foals?
OTC administered to neonatal foals with contracted tendens (high IV dose)
