Tetracyclines Flashcards
What drugs are included in tetracycline class?
-Tetracyline
-Oxytetracycline
-Chlortetracycline
-Doxycycline
Tetracycline
-licensed in food animals and horses
-water soluble powders or oral/intrauterine boluses
Oxytetracycline
-food animals only
-oral: feed premix or water soluble powder
-Intrauterine suspensions
-injectable products
*short acting= 100mg/ml LP formulations (IM or IV use)
*long acting= 200 or 300 mg/ml LA formulations (IM or SC use)
Human tetracycline products
Can be used extralabel in dogs/cats
How do oxytetracycline formulations become long acting?
Use carriers
*issue is that these carriers can be irritating
Chlortetracycline
-food animals
-oral premixes and boluses
Doxycycline
-used in small animals and horses
-no vet products; use human oral tablets (100mg). May need compounded forms to get size for small patients
Why can’t you use the smaller human capsules of doxycyclines in animals?
Modified release capsules so low dose
-likely not good bioavailability as it does not get released until colon
Tetracycline mechanism of action
-binds to bacterial ribosomal 30S subunit disrupting bacterial protein synthesis
-Need energy dependent transport into bacteria cells **animal cells lack tetracycline transporters
Tetracycline PK
-Typically bacteriostatic; bacteriocidal at high concentrations
-time dependent (prolonged exposure not high peak concentration)
-same antimicrobial activity and potency but some difference in efficacy/bioavailability
Tetracyclines spectrum of activity
-some gram +
-some gram - (resp pathogens)
-many anaerobes
-some mycoplasma
-tick borne bacteria
-Chlamydia
-protozoa
-spirochetes
What tick borne diseases can be treated with tetracyclines?
-Ehlichiosis
-Potomac horse fever (neorickettsia)
-Rocky mtn spotted fever (Rickettsia)
What do tetracyclines not effective against?
-Staphylococcus
-Gram - enterics
-pseudomonas
-enterococcus
rapid resistance emerging
Tetracycline susceptibility
Not uniform across bacterial species; lots of variance in MIC between individual isolates
Tetracycline mechanisms of resistance
- plasma mediated tet resistance genes
- decrease tetracycline in bacterial cell
-failure of active transport into bacterial cell
-increased efflux from the cell - Enzymatic inactivation of tetracycline
- Production of proteins that protect bacterial ribosomes
Tetracycline absorption
CTC/OTC= poor oral bioavailability (>20%)
Doxycycline: higher (50%)
*varies with feed status and formulation
Injectable OTC: high bioavailability
*LA formulations= flip flop kinetics= slow absorption which drives rate of elimination
Tetracycline oral bioavailability in pigs
-may see it as higher when fasted
-saw tetracycline and chlortetracyline higher bioavailability than OTC
Impact of variance for low bioavailability drugs?
Ex: 3+/- 3
Varies between 0 and 6
Means that there can be a huge difference between what is available to different individuals
**not really an issue when bioavailability is high because still getting drug into system
Distribution of tetracycline
-good distribution to most tissues and fluids
*Vd= 1L/kg in most species
-does not penetrate CSF well because P-gp will pump it out
-low/moderate protein binding except doxycycline (high 90%)
-bind to Ca/Mg so affects bones
Elimination of tetracycline
-Little metabolism
-small amounts of tetracycline is excreted in feces (biliary and intestinal P-gp)
*enterohepatic circulation can occur
-doxycycline will bind more= excreted in feces
-unchanged tetracyclines excreted by kidneys = urine
*useful for UTI
*longer half life with renal failure but dose modification not needed
Half lives or tetracyclines
6-8hours
*except LA injectable = 24hrs
Tetracycline adverse effects
- Nephrotoxicity possible but rare
*high doses and dehydration risk - Cardiovascular collapse with rapid IV injection
*thought maybe Ca binding but probably the carrier
**need to dilute and inject slowly
-long acting= IM/SC only - Chelation by Ca and heavy metals
-dont give oral tetracyclines with dairy products or antacids because decreased oral bioavailability
-teeth staining in young animals (not a big issue in vet med) - GI issues
-vomiting, diarrhea, - injection site reactions from drug carrier
Tetracyclines use in neonatal foals
-non-antimicrobial effect
-used to relax flexor tendons with angular limb deformity (contracted tendons)
-given as high IV dose
**might be due to mild anti-inflammatory effects
