Tetracyclines

Question 1

What drugs are included in tetracycline class?

Answer 1

-Tetracyline
-Oxytetracycline
-Chlortetracycline
-Doxycycline

Question 2

Tetracycline

Answer 2

-licensed in food animals and horses
-water soluble powders or oral/intrauterine boluses

Question 3

Oxytetracycline

Answer 3

-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)

Question 4

Human tetracycline products

Answer 4

Can be used extralabel in dogs/cats

Question 5

How do oxytetracycline formulations become long acting?

Answer 5

Use carriers
*issue is that these carriers can be irritating

Question 6

Chlortetracycline

Answer 6

-food animals
-oral premixes and boluses

Question 7

Doxycycline

Answer 7

-used in small animals and horses
-no vet products; use human oral tablets (100mg). May need compounded forms to get size for small patients

Question 8

Why can’t you use the smaller human capsules of doxycyclines in animals?

Answer 8

Modified release capsules so low dose
-likely not good bioavailability as it does not get released until colon

Question 9

Tetracycline mechanism of action

Answer 9

-binds to bacterial ribosomal 30S subunit disrupting bacterial protein synthesis

-Need energy dependent transport into bacteria cells **animal cells lack tetracycline transporters

Question 10

Tetracycline PK

Answer 10

-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

Question 11

Tetracyclines spectrum of activity

Answer 11

-some gram +
-some gram - (resp pathogens)
-many anaerobes
-some mycoplasma
-tick borne bacteria
-Chlamydia
-protozoa
-spirochetes

Question 12

What tick borne diseases can be treated with tetracyclines?

Answer 12

-Ehlichiosis
-Potomac horse fever (neorickettsia)
-Rocky mtn spotted fever (Rickettsia)

Question 13

What do tetracyclines not effective against?

Answer 13

-Staphylococcus
-Gram - enterics
-pseudomonas
-enterococcus

rapid resistance emerging

Question 14

Tetracycline susceptibility

Answer 14

Not uniform across bacterial species; lots of variance in MIC between individual isolates

Question 15

Tetracycline mechanisms of resistance

Answer 15

1. plasma mediated tet resistance genes
2. decrease tetracycline in bacterial cell
   -failure of active transport into bacterial cell
   -increased efflux from the cell
3. Enzymatic inactivation of tetracycline
4. Production of proteins that protect bacterial ribosomes

Question 16

Tetracycline absorption

Answer 16

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

Question 17

Tetracycline oral bioavailability in pigs

Answer 17

-may see it as higher when fasted
-saw tetracycline and chlortetracyline higher bioavailability than OTC

Question 18

Impact of variance for low bioavailability drugs?

Answer 18

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

Question 19

Distribution of tetracycline

Answer 19

-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

Question 20

Elimination of tetracycline

Answer 20

-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

Question 21

Half lives or tetracyclines

Answer 21

6-8hours
*except LA injectable = 24hrs

Question 22

Tetracycline adverse effects

Answer 22

1. Nephrotoxicity possible but rare
   *high doses and dehydration risk
2. 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
3. Chelation by Ca and heavy metals
   -dont give oral tetracyclines with dairy products or antacids because decreased oral bioavailability
   -teeth staining in young animals
4. GI issues
   -vomiting, diarrhea,
5. injection site reactions from drug carrier