Today's Veterinary Practice

NOV-DEC 2018

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PEER REVIEWED 32 NOVEMBER/DECEMBER 2018 todaysveterinarypractice.com in the central nervous system ( FIGURE 2 ), a mechanism akin to that of ketamine, which reverses or prevents central sensitization. A key component of central sensitization is the opening of NMDA receptors with subsequent transmission of excitatory electrical signals. Why Use Amantadine? Amantadine plays a role in pain control because central sensitization, often called central plasticity, 3 can be a stand-alone component of moderate to severe and/or undertreated pain and is a major component in the development of neuropathic pain. Which Patients Should Receive Amantadine? Amantadine should be considered as part of the initial multimodal therapy for any patient that has moderate to severe chronic pain and as an add- on drug for patients that have worsening chronic pain despite presumably adequate pain control and no worsening of the inciting disease. What Is the Dosage for Amantadine? Because amantadine's contribution to pain relief is not really analgesia (it is technically called antihyperalgesia), the drug must be used as part of a multimodal protocol with true analgesic drugs like NSAIDs, opioids, and gabapentin. The dosage for dogs and cats is 3 to 5 mg/kg PO q24h to q12h, with q12h preferred. Data from recent pharmacokinetic studies indicate that twice daily dosing is probably more effective than the traditional once daily dosing in dogs 24 and cats. 25 To decrease the central sensitization component of chronic pain, treatment duration probably needs to be long; thus, the current minimum duration recommended is 21 days. 26 Longer durations may be necessary, and many patients may need amantadine for life. What Efficacy Data Are Available for Amantadine? Less information is available about the use of amantadine than use of gabapentin for the treatment of chronic pain in veterinary patients, but 1 controlled research study of dogs with chronic refractory hindlimb osteoarthritis has been reported. 26 In that study, dogs receiving NSAIDs plus amantadine (3 to 5 mg/kg PO q24h for 21 days) were more active and scored lower on a lameness scale than dogs receiving NSAIDs alone. Researchers of a study of heat-induced pain in cats receiving oxymorphone concluded that "amantadine might decrease the antinociceptive (analgesic) dose of oxymorphone in some but not all cats." 27 These results are not surprising because the mechanism of action of amantadine is more likely to be effective in animals with central sensitization, which was not caused in this research model. As stated in the discussion of gabapentin, there is a scarcity of studies on treating chronic pain with any drug or modality in veterinary patients. What Are the Adverse Effects of Amantadine? No adverse effects or drug interactions in dogs or cats receiving amantadine have been reported. 7 How Is Amantadine Supplied and What Does It Cost? Amantadine is moderately expensive. Amantadine is supplied as tablets and capsules of various strengths and can be compounded as a liquid without xylitol. Are There Any Other Drugs in This Class (NMDA-Receptor Antagonists) That Are Used for Pain Relief? Ketamine, which is used as an infusion to provide analgesia, is used for acute pain relief, and reports from human medicine show that it can be used to treat some forms of chronic pain. 28 Methadone, a potent opioid, also has some NMDA-receptor antagonistic effects. Other oral drugs in this class Your first choice for known nerve damage should be gabapentin, and your first choice for pain that is suddenly worse than expected with no signs of worsening disease should be amantadine.

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