Guidelines for theUse of Analgesics and Tranquilizers in Laboratory Animal4

Other Analgesics

Analgesics are pain relievers most often given after a surgery. Narcotic analgesics have already been described above. Nonsteroidal antiiflammatory drugs (NSAIDs) may also be used for their analgesic effect.  The NSAIDs consist of drugs like aspirin, ketoprofen, acetaminophen, flunixin and ketorolac. There are a large number of these drugs available, however, relatively few are used in animals. NSAIDs are, in general, less potent analgesics than are the narcotics. However, in specific instances they can have similar activity. 

The advantages of the NSAIDs are that they do not cause sedation nor are they addictive as are the narcotic analgesics. There are no special recordkeeping requirements. In addition, they are more effective against pain caused by inflammation, such as is seen with tissue repair, orthopedic surgery, infection and injury. 

The NSAIDs have several side-effects related to their pronounced anti-prostaglandin (anti-cyclooxygenase and in some cases lipooxygenase) activity. This is peripheral with most drugs, but is primarily central with acetaminophen. These effects can alter immune function, platelet function and can cause gastrointestinal ulceration. In addition, the NSAIDs all have the potential to cause nephro- and hepatotoxicity. This is variable among species. Cats, in particular, are sensitive to the NSAIDs. Acetaminophen is contraindicated is cats due to risk of methemoglobinemia. 

Acetaminophen- mild analgesic, antipyretic, no effect on platelet function/bleeding time 

Aspirin- mild analgesic, antipyretic, antiinflammatory, affects platelet function/bleeding time 

Carprofen is a nonsteroidal antiinflammatory drug with antiinflammatory and analgesic effects and lower risk for toxicity in animals than other NSAIDS. 

Flunixin meglumine (Banamine)- potent analgesic, antiinflammatory, antipyretic. Has potential for GI ulceration, hepato- and nephrotoxicity. 

Ketoprofen- moderate potency analgesic, antiinflammatory, antipyretic. Has potential for GI ulceration, hepato- and nephrotoxicity, affects platelet function/bleeding time. 

Ketorolac (Toradol)- potent analgesic, antiinflammatory, antipyretic. Has potential for hepato- and nephrotoxicity, less potential for GI ulceration than other NSAIDs, affects platelet function/bleeding time. 

Acetaminophen Update 
Alternatives to acetaminophen in rats and mice

Anesthetic Drug Combinations

In general, by mixing anesthetic and analgesic drugs, the dose required for each individual drug is reduced, sometimes quite dramatically. Start at the low end of the dose range listed; you can always give more if needed!  Drugs not listed below can be mixed using the same concepts, mix a sedative or hypnotic with an analgesic. Do not mix drugs in the syringe until you have determined that they are compatible when mixed. If in doubt administer separately. 

Determining expiration dates for mixed/diluted anesthetic or pain relieving drugs: In the absence of empirical evidence, expiration dates of diluted or mixed drugs will be determined as follows:

1. Manufacturer抯 dating of the drugs to be mixed together will determine the expiration date if shorter than the timelines given below.

2. Mixed anesthetic drugs (ketamine, xylaxine, acepromazine, butorphanol, telazol): Expiration date is 30 days after mixing, based on Minnesota Board of Pharmacy recommendations.

3. Diluted drugs (buprenorphine) - Expiration date is 30 days from dilution date.

4. Avertin - All solutions should be discarded 4 months after mixing, including stock solutions. pH should be tested prior to every use. Solution should only be used if pH is greater than 5. See http://www.ahc.umn.edu/rar/avertin.html

5. Any substance which shows signs of precipitation, change of color, change in transparency or other signs of transformation should be immediately discarded.

6. All diluted/ mixed substances must be combined into sterile containers (unless the combination is for a single acute procedure and the mixture will not be stored).

Ketamine/Diazepam: Mix drugs 1:1 by volume and administer 0.1 ml/kg IV for restraint, anesthetic induction or for non-painful procedures. This gives excellent muscle relaxation, has minimal respiratory or cardiovascular depression and the animals wake up smoothly and quickly (within 10-15 min). Visually, these drugs do not appear to mix completely. When combined and administered as described, the dose is 5 mg/kg ketamine and 0.25 mg/kg diazepam.

Ketamine/Acepromazine: Mix 10 mg acepromazine (1 ml) with 1 g (10 ml) ketamine and give 0.1-0.3 ml/kg mixture IM or IV (up to 0.6 ml/kg in rodents and rabbits). Good for restraint, but not for painful procedures. When combined and administered as described, the dose is 0.09-0.27 mg/kg acepromazine and 9-27 mg/kg ketamine.

Acepromazine/Butorphanol: Mix drugs 1:1 by volume (using 10 mg/ml butorphanol) and administer at 0.01-0.02 ml/kg IV or IM. Creates a hypnotic state that is good for restraint and minor procedures that cause some pain. When combined and administered as described, the dose is 0.05-0.1 mg/kg butorphanol and 0.05-0.1 mg/kg acepromazine.

Ketamine/Acepromazine/Butorphanol: Mix 10 mg acepromazine (1 ml), 10 mg butorphanol (1 ml) with 1 g (10 ml) ketamine and give 0.1-0.3 ml/kg of mixture IM or IV (up to 0.6-0.8 ml/kg in rodents and rabbits). Good for restraint and moderately painful procedures. More cardiac and respiratory depression will be seen with this mixture than with ketamine alone. When combined and administered as described, the dose is 8-25 mg/kg ketamine, 0.08-0.25 mg/kg acepromazine, and 0.08-0.25 mg/kg butorphanol. For rodents & rabbits, the dose is 50-67 mg/kg ketamine, 0.5-0.7 mg/kg acepromazine, and 0.5-0.7 mg/kg butorphanol.

Ketamine/Xylazine: Good for restraint and painful procedures. Administer IM, IP, or IV. More cardiac and respiratory depression will be seen with this mixture than with ketamine alone. Use 100 mg/ml ketamine and 20 mg/ml xylazine to create any of the mixtures listed below.

CAUTION: DO NOT USE this cocktail of ketamine-xylazine for cattle, sheep, goats, or other ruminants. Giving ketamine and xylazine simultaneously is not recommended for horses.

Ketamine/Midazolam/Butorphanol: Mix 0.4 ml each ketamine and midazolam with 0.01 ml of 10 mg/ml butorphanol and administer 0.8 ml/kg. This provides good muscle relaxation and surgical anesthesia in rodents. When combined and administered as described, the dose is 40 mg/kg ketamine, 2 mg/kg midazolam, and 0.1 mg/kg butorphanol.

Telazol/Xylazine: For pigs: reconstitute powdered Telazol (tiletamine & zolazepam) with 5 ml of xylazine instead of saline. For pigs < 50 kg, use 20 mg/ml xylazine to make the cocktail. For pigs > 50 kg, use 100 mg/ml xylazine. Administer at 0.05-0.1 ml/kg IV or IM. When combined and administered as described, the dose is 2.5-5 mg/kg tiletamine, 2.5-5 mg/kg zolazepam, and either 1-2 mg/kg xylazine (if 20 mg/ml xylazine was used) or 5-10 mg/kg xylazine (100 mg/ml xylazine). For rats, use 20 mg/ml xylazine and administer up to 0.4 ml/kg IM. Here, the dose can be as high as 8 mg/kg xylazine, 20 mg/kg tiletamine, and 20 mg/kg zolazepam.
More cardiac and respiratory depression will be seen with this mixture than with Telazol alone.
Reversal with yohimbine 0.1-0.15 mg/kg (IM or IV) or atipamezole at 0.25 (IM) or 0.2 (IV) mg/kg is recommended to shorten recovery times.
CAUTION: DO NOT USE this cocktail of Telazol-xylazine for mice, rabbits, or ruminants such as cattle, sheep, , or goats. Giving Telazol and xylazine simultaneously is not recommended for horses (contact an RAR veterinarian for more information).