Chapter 35 Use of Analgesics in Exotic Felids
Treatment of pain in domestic and nondomestic cats has been a challenge for the clinician. Many cat species are stoic and show few or subtle external signs of pain. Additionally, the adverse effects of nonsteroidal antiinflammatory drugs (NSAIDs) in domestic cats are well documented and have discouraged many practitioners from trying novel NSAIDs in exotic felids.
As in other animals, each cat’s response to pain and analgesics will vary, necessitating an individualized treatment plan. As a rule, always treat painful felids to effect, not by rote reliance on published dosages. It is frequently necessary to try different agents and combinations to find which produces the optimal analgesic effect in exotic felids. To minimize adverse effects, work toward treatment with the lowest effective dose when treating chronic pain.
The NSAIDs act both centrally and peripherally. The primary effects are believed to be caused by the ability of NSAIDs to inhibit cyclooxygenase (COX) enzymes in the arachidonic acid metabolism cascade. The COX-1 isoform is regarded as constitutive (continuously expressed) and is responsible for many homeostatic processes, such as maintenance of gastric mucosal integrity, platelet function, and renal autoregulation. Reduced COX-1 activity is believed to be responsible for many of these agents’ adverse effects. The COX-2 isoform is generally thought to be induced in response to noxious stimuli and initiates creation of proinflammatory prostaglandins. Inhibition of the COX-2 isoforms prevents the production of these prostaglandins and the associated pain. This simplification of COX and NSAID physiology is under constant revision but remains the basis for categorizing the activities of NSAIDs. All drug dosages, unless otherwise indicated, are as listed in Table 35-1.
Aspirin is the only NSAID for which a safe chronic dosage has been established in cats, but it has been largely replaced in practice by newer NSAIDs. Aspirin has antiinflammatory, antiplatelet, and analgesic effects but is not effective for severe pain. Cats lack the ability to bind many compounds to glucuronides and do not metabolize and excrete salicylates well. As a result, aspirin must be given at a less frequent dosing interval in cats than in most other mammals. Vomiting and gastric hemorrhage are the two major adverse effects seen with aspirin administration.
Ketoprofen and carprofen are propionic acid derivatives with analgesic and antiinflammatory properties. Ketoprofen is approved for use in cats in Europe and Canada, in both injectable and oral preparations. Ketoprofen is considered a COX-1 preferential agent and provides good postoperative analgesia in cats, but it reduces platelet activity and therefore is not recommended for administration before surgery. Short-term treatment (up to 5 days) has been investigated in domestic cats, but longer-term therapy has not been studied.
Carprofen is not approved for use in cats in the United States but is approved as a single-dose agent in Europe. It is considered a COX-2 preferential agent and has been studied as a perioperative analgesic for cats. Several authors caution against long-term use of carprofen in cats,11 and there is an anecdotal report of a leopard dying with intestinal ulcers after 2 weeks of carprofen therapy.
Meloxicam is an enolic acid compound with analgesic, antiinflammatory, and antipyretic activities, and it is considered a COX-2 preferential NSAID. It is approved for use in cats in Europe and the United States. The injectable form is approved for single-dose administration, and the oral form is approved for administration up to 5 days. Both the oral and the injectable forms of meloxicam have been used for extended periods in domestic and nondomestic felids with few, if any, adverse effects.
Piroxicam is not related structurally to other NSAIDs but is considered a COX-1 preferential agent. It has antiinflammatory and analgesic properties but has been used most frequently in domestic animals, especially dogs, for its antineoplastic effects. In dogs there appears to be a narrow window of therapeutic safety, and other NSAIDs are considered safer alternatives for analgesia. Few studies of piroxicam’s use in cats have been published.
Opioids produce their effects by binding with specific opiate receptors. Historically, veterinarians were reluctant to use this class of drugs in cats because opioids were reported to cause dysphoria, mania, and excitement. These effects were most likely dose-related or route of administration–related responses, and opioids are now routinely used for analgesia in domestic cats. Other adverse opioid effects in cats include respiratory depression, loss of thermoregulatory ability, sedation, nausea, vomiting, and mydriasis. Effects will vary with the agent and dosage, but large cats seem more susceptible to these nonanalgesic effects, on a comparable dose basis, than domestic cats. All opioids have the advantage of their effects being terminated by administration of an opioid antagonist, of which naloxone is the safest.
Morphine, oxymorphone, hydromorphone, and meperidine are mu-receptor agonist opiates that have been used in domestic cats for postoperative pain. Morphine is the agent most often associated with causing dysphoria or excitement in cats. All these drugs are controlled substances (U.S. Drug Enforcement Administration Category II), and their use in many practices has largely been replaced by the less stringently controlled opioid analgesics, buprenorphine and butorphanol. The latter agents, however, are not as potent as the pure mu-receptor analgesics.
Fentanyl is a mu-receptor agonist opiate that has gained widespread use as a postsurgical analgesic in domestic species because of its formulation in a transdermal delivery system (patch). Transdermal delivery offers the advantages of a long duration of delivery and effects (≤72 hours) and the ability to stop administration (by patch removal) if necessary. After patch application in domestic cats, there is a lag time of 6 to 8 hours before analgesic effects. As a result, additional analgesia is required to bridge the period between patch administration and onset of analgesia. Patches need to remain in good contact with the skin to be effective; this typically requires bandaging, which is difficult to maintain in nondomestic felids. As a result, fentanyl patches can be used only in select nondomestic felids.
Buprenorphine is a partial mu-receptor agonist with potent analgesic properties. It is available in the United States only in the injectable form, but this preparation may also be administered to cats transmucosally, via the oral mucous membranes. Onset of analgesia after oral transmucosal administration is more rapid than when used intramuscularly and is a potential way to administer this drug following recovery from surgery.9 Buprenorpine has relatively few adverse effects when used at recommended dosages and has the distinct advantage of a long duration of activity (>6 hours).
Butorphanol is a mu-receptor antagonist that produces analgesia through its binding to kappa receptors. This combination of receptor affinities results in a ceiling effect to its analgesic and adverse effects, a dosage point above which there is no increase of effects. Butorphanol appears to provide analgesia to the viscera but poor body wall or muscular analgesia. In addition, butorphanol is relatively short acting (<2 hours), and effective analgesia after major surgery requires frequent redosing. Large cats seem particularly susceptible to butorphanol’s sedative effects.
Tramadol, although structurally not an opioid, has weak affinity for mu receptors. Its principal mechanism of analgesic action appears to be by inhibiting reuptake of serotonin and norepinephrine within the spinal cord; as a result, tramadol appears to modulate pain at the spinal level. It does not affect COX enzymes and may be given safely in combination with NSAIDs. It has few adverse effects, although dose-dependent respiratory depression has been observed in anesthetized domestic cats. Tramadol appears to have an extremely low risk of dependency, but it is recommended that animals receiving long-term therapy be weaned off treatment slowly. Tramadol is not a controlled agent in the United States and is available only in an oral form.