Abstract
Analgesia in mammals can be achieved with nonsteroidal anti-inflammatory (NSAIDs) agents, opioid agonists (OA), opioid agonist-antagonists (OAA), and alpha-2 adrenergics (A2A). Other anti-inflammatory agents, such as glucocorticoids, may provide indirect analgesia.
NSAIDs have anti-inflammatory, anti-prostaglandin and analgesic effects. The anti-inflammatory and anti-prostaglandin activity results from inhibition of the enzyme cyclo-oxygenase (prostaglandin synthetase).1,6,7 Gastric ulceration is a potentially serious side effect of NSAID administration because the protective mucosal barrier of the stomach may be reduced by inhibition of prostaglandin E production. A few of the newer generation NSAIDs such as carprofen are more sparing of prostaglandins and are less ulcerogenic. Some NSAIDs are also nephrotoxic, especially when administered to an animal that has pre-existing renal compromise or hypotension, as may occur under anesthesia. Additionally, NSAIDs have high protein-binding potential, which can influence the metabolism of other drugs. NSAIDs also interfere with the production of glycosaminoglycan by injured chondrocytes and may worsen joint disease with prolonged administration.1 At present, NSAIDs that can be given parenterally or orally are limited to flunixin meglumine, ketoprofen and ketorolac.
OAs provide excellent analgesia and have high therapeutic ceilings. The greater the dose used, the more analgesia achieved.2-4,8 They are especially useful for the control of moderate to severe pain but have no anti-inflammatory or anti-prostaglandin effects. OAs have shorter systemic than local duration. Examples of opioids used on animals are morphine, codeine, fentanyl, fentanyl transdermal patches and oxymorphone. Side effects include drowsiness, respiratory depression, urinary retention, nausea and vomiting. They should not be used when head injury is present because the respiratory depression can decrease CO2 levels, which will cause cerebral vasodilation and an increase in intracranial pressure. Most opioids are available in oral as well as parenteral formulations.
OAAs cause less cardiopulmonary depression but have less analgesic effect than OAs.2-4 They have agonist activity at opioid k receptors but minimal effects at opioid m receptors (sedation and respiratory depression centers). However, because they have a low therapeutic ceiling, higher dosages will not increase analgesia. Examples of OAAs are butorphanol, pentazocine, buprenorphine, and meperidine.
A2As provide potent analgesic effects and sedation in some species, and potentiate opioid analgesia in others.2,3 They have cardiovascular side effects, which may limit their use to young healthy animals. Xylazine, medetomidine, and detomidine are examples of A2As.
Babirusa (Babyrousa babyrussa), a Southeast Asian suid, have been maintained at the Wildlife Conservation Society (Bronx Zoo) since 1985. As original breeding stock has aged, and offspring have matured, unusual numbers of animals have developed acute and chronic arthritides and degenerative joint disease (DJD). Multifactorial etiologies are probably responsible for the severity of some lesions. As with other suids, an interplay of infectious disease, nutritional factors, genetics, housing conditions, and traumatic events in individuals may result in varying degrees of acute and chronic pain.5 While underlying causes of lameness are treated or corrected, analgesia is a critical element of all therapeutic and management plans.
NSAIDs have been used most frequently in an attempt to provide relief from discomfort and to decrease joint inflammation. Dosages were determined by synthesizing information from the human and veterinary literature. As with any non-labeled use of drugs, conservative treatment plans are followed when using any agent for the first time. Fecal occult blood is routinely monitored in animals receiving any NSAID for more than 3 days. If occult blood is detected, GI protectants such as sucralfate (Carafate tablets, 1 g, Hoechst Marion Roussel), and histamine-2-receptor antagonists [cimetidine (Tagamet, 300 mg tablets, SmithKline Beecham, Philadelphia, PA 19101 USA) or ranitidine (Zantac, 300 mg tablets, Glaxo Wellcome, Research Triangle Park, NC 27709 USA)] are administered.
Acute onset of single limb lameness is most often treated with flunixin meglumine (Banamine Solution 50 mg/ml, Schering-Plough Animal Health, Kenilworth, NJ 07033 USA) (0.5-1.0 mg/kg PO SID–BID). Animals which are non-responsive after 3–5 days may be darted with flunixin (1 mg/kg SID) for 1–2 days. Oral flunixin as needed is continued when necessary. One adult male with repeated bouts of acute pain associated with chronic DJD improves dramatically with minimal flunixin doses (0.15 mg/kg PO) as required.
Some persistent lamenesses have responded to ketoprofen (Ketoprofen capsules 75 mg, Biocraft Laboratories, Elmwood Park, NJ 07407 USA) ( 0.3–0.8 mg/kg PO SID–BID) for 3–10 days. Aspirin has not provided adequate analgesia at 10–20 mg/kg PO BID. Ibuprofen (Ibuprofen tablets 200 mg, Interpharm Inc., Plainview, NY 11803 USA) (15 mg/kg PO BID) is occasionally used with variable results. Carprofen (Rimadyl 100 mg tablets, Pfizer Animal Health, Exton, PA 19341 USA) (4–6 mg/kg PO BID) was not effective in providing relief in one case of severe chronic DJD, and at the higher dose, fecal occult blood was present.
Transdermal fentanyl patches (Duragesic 50 mg/h, Janssen Pharmaceuticals, Titusville, NJ 08560 USA) have been used 3 times on 2 animals that had severe pain due to chronic DJD. The animals refused to rise or move about their enclosures. There had been no, or poor, response to administration of NSAIDs (flunixin, ketoprofen and carprofen). Response to the fentanyl patch was dramatic, with the animals becoming fully ambulatory within 24 h of receiving a dose of 50 mg/h fentanyl. The effect of the patch was so complete in breaking the pain cycle, that one animal which had been treated repeatedly with NSAIDs during the previous year remained asymptomatic for 5 mo. Two animals, with gradual onset of severe unilateral front limb lameness and reduction of mobility, did not improve with the use of fentanyl patches. Transdermal patches work best when oil and debris are removed from the skin with alcohol prior to application. The patch itself has an adhesive edge which is augmented by placing an elastic adhesive bandage over it and around the limb to which it is applied. Patches have been most efficacious when applied to the medial aspect of the upper forelimb.
Depending on the severity of lesions and the temperament of the individual animal, pain in babirusa can be debilitating. Failure to provide analgesia while also treating the underlying cause of the pain may result in overall failure of therapy.
Acknowledgments
The contributions of Mark Stetter, DVM to the management of these cases and the extraordinary care provided by the mammal department keepers during some of the protracted clinical courses is appreciated, as is the assistance of Peter Helmer with literature searches.
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