Opioid and tramadol use in outpatients: What are reasonable choices? (Proceedings)


Opioid and tramadol use in outpatients: What are reasonable choices? (Proceedings)

Aug 01, 2010

Nonsteroidal antiinflamatory drugs (NSAIDs) are commonly used in veterinary medicine for a variety of reasons including the management of acute postoperative pain and chronic pain associated with degenerative joint disease among other conditions. However adverse effects preclude their use in many patients and severe adverse effects such as nephrotoxicity, hepatotoxicity, and gastrointestinal ulceration and perforation, and death occur infrequently. A variety of other medications have demonstrated efficacy in humans, but information on their use and efficacy in veterinary medicine are lacking. Fentanyl patches have been used successfully to manage pain in dogs and cats, but liability and abuse potential are concerns in veterinary medicine.

A variety of oral opioids have been evaluated in dogs. Pharmacokinetic studies examining morphine, methadone, butorphanol, and oxycodone indicate they have poor systemic absorption after oral dosing and are unlikely effective. The oral absorption of codeine is also limited as well as the formation of the active metabolite morphine in dogs. However recent studies indicate another metabolite, codeine-6-glucuronide (C6G) may produce analgesic effects in humans. Dogs may produce C6G in large amounts after codeine administration, but data are extremely limited.

Hydrocodone. Studies evaluating the oral bioavailability of hydrocodone in dogs have shown variable results (~40-80%) but indicate it is absorbed systemically following oral administration to dogs. Hydrocodone is mu opioid agonist most commonly used in veterinary medicine as an antitussive; however it is routinely used in humans as an analgesic. Hydrocodone is metabolized to hydromorphone, an active metabolite which is also a mu agonist. Recent studies in dogs suggest that hydrocodone is metabolized to hydromorphone in dogs with hydromorphone concentrations persisting to at least 8 hours after 0.5 mg/kg hydrocodone bitartrate PO. The analgesic effects of hydrocodone have not been determined in dogs. Hydrocodone tablets containing 10 mg hydrocodone bitartrate and 300 mg acetaminophen can be quartered with relatively good precision, therefore a dose of ΒΌ tablet per 11# of body weight to dogs q 8-12 hours PO can be administered. Hydrocodone is inexpensive, but is subject to abuse. Therefore it may be best not to stock hydrocodone in the clinic, but script it out to a local pharmacy to decrease liability potential. Do not administer the combination product to cats as the acetaminophen is toxic to cats.

Tramadol. Tramadol is a central acting analgesic with multiple mechanisms of action. Tramadol and its active metabolite (o-desmethyltramdol or M1) are serotonin and norepinephrine reuptake inhibitors which may contribute to its analgesic effects by stimulating descending pain inhibitory pathways. Tramadol's active metabolite also appears to act through the mu opiate receptors to elicit analgesic effects. Although no efficacy studies are available in dogs, studies in humans demonstrate the metabolite is necessary for tramadol to be effective as an analgesic. Studies in dogs and cats have identified the active metabolite, although the formation appears variable. Selective serotonin reuptake inhibitors (SSRI's), such as fluoxetine and paroxetine, inhibit the metabolism of tramadol to the active metabolite decreasing its efficacy and increasing the risk of toxicity (serotonin syndrome). Other drug-drug interactions due to serotonin toxicity with tramadol include tricyclic antidepressants (clomipramine, amitriptyline) and serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine). Ondansetron (Zofran) and other serotonin antagonists (5HT3) may decrease the efficacy of tramadol, but the results have been variable. Tramadol is inexpensive and currently not a scheduled drug in the USA. Tramadol may lower the seizure threshold, therefore should be used cautiously in animals prone to seizures such as epileptics. Current dosing recommendations for dogs are 5 mg/kg q 6-8 hours and for cats 1-2 mg/kg q 12 hours. The efficacy of these dosages has not been evaluated. It is important to remember that maximum analgesic effects may not occur immediately and may be delayed up to 10-14 days for chronic pain conditions such as cancer and degenerative joint disease. Tramadol can be administered with NSAIDs, gabapentin, and amantadine.

Codeine. Codeine has been recommended for use in dogs at a dose of 1.1-2.2 mg/kg PO q 6-12 hours. The oral bioavailability of codeine in dogs is low, ~ 4%, compared to ~ 60% in humans. Approximately 10% of codeine in metabolized to morphine in humans, but morphine was not detected in dogs after oral administration of codeine 2 mg/kg PO. However large amounts of a metabolite, codeine-6-glucuronide, were formed in dogs which may provide an analgesic effect. The efficacy of oral codeine in dogs has not been demonstrated.