Dexdomitor and adjunctive analgesic drugs (Proceedings)

Alpha 2 Adrenergic Agonists

Alpha 2 adrenergic agonists bind to alpha 2 receptors located in the dorsal horn of the spinal cord and brainstem, modulating the release of substance P, calcitonin gene-related peptide and various other neurotransmitters involved in rostral transmission of nociceptive information. Opioids likely exert their analgesic action through similar modulatory pathways and co-administration may result in additive or synergistic drug interactions. In humans alpha 2 agonists are often used as "rescue therapy" when opioid tolerance has developed. Use in surgical patients should be reserved for patients that have been stabilized with normal cardiopulmonary function.

Dexdomitor - FDA-approved indications

1. Sedation and analgesia in cats as young as 12 weeks of age

2. Sedation and analgesia in dogs as young as 16 weeks of age

3. As a preanesthetic prior to general anesthesia in dogs, for concurrent use with commonly used induction and anesthetic agents

Sedation and Analgesia in Cats

A label indication for use in cats is a new feature of Dexdomitor when compared to Domitor. Although Domitor was used in cats however this was off-label. The dose of dexmedetomidine is approximately 20-40 mcg/kg. The IM route of administration is convenient when handling stressed patients, but intravenous administration will usually result in a faster onset of action. Dexmedetomidine is suitable for various short-term feline procedures, specifically for procedures requiring sedation and/or analgesia but not requiring intubation. The reversal agent atipamezole (Antisedan) is not approved for use in cats, however previous experience with atipamezole reversal of Domitor in cats suggests it is effective.

Sedation and Analgesia in Dogs

Flexible dosing is a new label indication for Dexdomitor in dogs. A low dose of 375 mcg/m2 IV vs a higher dose of 500 mcg/m2 IM was approved to facilitate following label directions, yet keeping the dose as low as possible to provide sedation and analgesia. It should be remembered that reducing the dose does not prevent the cardiovascular changes associated with all alpha 2 agonists (increased vascular resistance and lowered cardiac output) but should reduce the duration of these effects and in some individuals reduce the peak effect.

Preanesthesia in Dogs

Dexdomitor is now FDA-approved for concurrent use with commonly used induction and anesthetic agents, and has proven safe for use in dogs as young as 16 weeks of age. Although some veterinarians had previously used Domitor as a preanesthetic, this was extra-label. There are two approved dosing options for use as a preanesthetic: 125 mcg/m2 given IM for cooperative sedation that allows most dogs to remain ambulatory, a useful option for larger patients or 375 mcg/m2 given IM for deeper sedation, a useful option for patients requiring procedures of extended duration or associated with severe pain. The choice of preanesthetic dose depends on patient disposition, severity and duration of procedure, and the anesthetic protocol. It must be remembered that Dexdomitor markedly reduces anesthetic requirements for all induction drugs including propofol or ketamine and maintenance using isoflurane or sevoflurane.

Adjunctive Analgesic Drugs

Adjunctive drugs are typically used for the treatment of chronic pain. They have varying mechanisms of action and provide an opportunity for utilizing a diverse group of receptor types to treat pain that is refractory to traditional analgesics such as opioids and NSAIDs. There is increasing interest in the use of some adjunctive drugs in combination with opioids or NSAIDs for the multimodal treatment of acute pain. The safety and effectiveness of adjunctive drugs are generally not well studied in veterinary patients therefore responsibility lies with the veterinarian when they are used extra-label.

Gabapentin

Gabapentin is an anticonvulsant that has been used for some time in human and veterinary medicine as an adjunctive treatment for neuropathic pain. Anecdotally, the drug appears effective in a limited number of individuals, but when effective can make a significant difference in the patient's quality of life. Oral administration of human-labeled capsules or liquids is most common. Oral bioavailability can vary significantly between individuals; therefore individual dose titration is often required. When terminating chronic administration, tapered reduction of the dose is recommended over several weeks.

Amantadine

Amantadine is a human-labeled anti influenza drug. Its other uses include treatment of Parkison's disease symptoms and chronic pain. It has analgesic effects mediated by NMDA receptor antagonism and anecdotally is effective for prevention and treatment of central sensitization. It is most commonly used in conjunction with NSAIDs for refractory cases of canine osteoarthritis.

Ketamine

Ketamine has been extensively used at sub-anesthetic doses as an adjunctive treatment for the prevention of chronic pain. Its use as a treatment of existing pain is limited due to lack of an oral formulation. It is commonly administered as a continuous rate infusion to patients during anesthesia or hospitalization. The main mechanism of action appears to be NMDA receptor antagonism. Ketamine also is a useful somatic analgesic which may be partially responsible for its usefulness in prevention of surgical pain. Adverse psychological effects of ketamine, and other NMDA receptor antagonists have limited their widespread use in human medicine.

Pregabalin

Pregabalin (Lyrica®) is a relatively new human product labeled for the treatment of chronic pain associated with diabetic neuropathy and postherpetic neuralgia. Its pharmacology is very similar to gabapentin. Use in veterinary patients has not been evaluated.

Antidepressants

Tricyclic antidepressants such as amitriptyline have been used for treatment of chronic pain in humans. There use in veterinary patients is probably not as common as gabapentin and amantadine. Adverse effects of this class can limit usefulness, although generally they do not result in long term harm. Drug interactions are common with this class and should be monitored when multiple drug classes are administered.

Nonpharmacologic Therapy

In addition to drug intervention, there are a number of nonpharmacologic methods being employed to supplement analgesia. The importance of good nursing care in animals recovering from surgery cannot be overemphasized. Techniques such as physiotherapy, chiropractic or massage therapy may help to alleviate pain following trauma, and may facilitate an earlier return of function.