Tetracyclines

Question 1

What are the 4 different tetracycline drugs?

Answer 1

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

Question 2

Why are tetracyclines irritating on injection?

Answer 2

likely due to carriers in formulation

- biomycin a little less irritating

Question 3

What is the MOA of tetracyclines?

Answer 3

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

Question 4

What is the PK-PD relationship of tetracyclines?

Answer 4

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

Question 5

What is the spectrum of activity of tetracyclines?

Answer 5

effective
- some gram + and -, many anaerobes, some mycoplasma, some rickettsia, chlamydia, protozoa and spirochetes

less/not effective
- often staph resistant, gram - enterics, pseudomonas, enterococcus

Question 6

is their resistance emergence?

Answer 6

emerges rapidly often alot of variance

• has been used for growth promotion
• if used for prevention must be used in max potential (feed)

Question 7

What is the mechanism of tetracycline resistance?

Answer 7

plasma mediated tet gene (limits clinical usefulness)
failure in active transport of drug into bacteria
increased efflux
production of proteins that protect ribsome

Question 8

What is the PK of absorption of tetracyclines?

Answer 8

oral F
CTC/OTC poor
doxycycline: much higher
injectable OTC
- high

Question 9

What is unique about injectable OTC and PK?

Answer 9

high F

LA formulation = flip flop kinetics
- elimination much slower in IM or IV
IM still absorbed as eliminated

Question 10

Shown in pig study, how does the bioavailability change fed or fasted?

Answer 10

much higher in fasted state

tetracyclines are ineffective againist enteric pathogens (wont absorb anyway)

Question 11

What is the PK distribution of tetracyclines

Answer 11

good in most tissues and fluids
- CSF not good (pgyp)
low to moderate protein binding
except DXC

Question 12

What is unique about TC distribution?

Answer 12

TCs bind to Ca/Mg

deposition in bones and teeth

Question 13

What is the PK elimination of tetracyclines?

Answer 13

very little metabolism
some TC excreted in bile, intestine (pgyp)

enterohepatic recirculation

unchanged drug excreted via glomerular filtration

Question 14

What is significant about unchanged drug being excreted in the kidney? what is the exception

Answer 14

high concentrations in urine

• used for UTI
• longer T-1/2 with renal failure

doxy excreted in feces

Question 15

What is the T1/2 orally and with LA injectable?

Answer 15

6-8h

24h

Question 16

what are the adverse effects of tetracyclines? (generally safe, but)

Answer 16

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)

Question 17

What are the significant adverse MSK effects that can occur with OTC? what is the mechanism?

Answer 17

relax flexor tendons

Mechanism: inhibition of matrix metalloproteinase enzymes

Question 18

What tetracycline can be used to treat contracted tendons in neonatal foals?

Answer 18

OTC administered to neonatal foals with contracted tendens (high IV dose)