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Alpha-2 agonists and analgesia (Proceedings)
In the veterinary profession, ?-2 adrenergic receptor agonists (?-2 agonists) are either loved or feared; this is often determined by a veterinarian's familiarity with the drug. There is no doubt that ?-2 agonists have complex effects, but understanding ?-2 agonists increase options for analgesic use, as well as sedation.
In the veterinary profession, α-2 adrenergic receptor agonists (α-2 agonists) are either loved or feared; this is often determined by a veterinarian's familiarity with the drug. There is no doubt that α-2 agonists have complex effects, but understanding α-2 agonists increase options for analgesic use, as well as sedation.
There are benefits to incorporating α-2 agonists into regular practice. Firstly, and the focus of this lecture, is the analgesic benefits for the patient. α-2 receptors are found pre and post synaptically in neuronal tissue, such as the dorsal horn of the spinal cord. The analgesic benefits of α-2 agonists are mediated primarily, but not exclusively, at the dorsal horn. The analgesic benefit for the patient is not dependent on the level of sedation, as it appears the level of sedation is actually mediated supraspinally, in the locus ceruleus. However, this supraspinal action of α-2 agonists may also assist in modulation of descending transmission of nociception. This combination of spinal and possibly supraspinal analgesia is a powerful tool. While veterinarians are often employing analgesic drugs in acutely painful situations, such as with a surgery, α-2 agonists have also been useful as adjunctive analgesia for chronic pain conditions, such as cancer. In addition to α-2 agonists' individual actions in pain modulation, these drugs may also work synergistically with opioids to enhance analgesia (Slingsby, Murrell and Taylor 2010).
There are other benefits from these drugs. The level of sedation and muscle relaxation obtained from administration of an α-2 agonist is quite profound. This facilitates performing, as well as providing analgesia, for many minor diagnostic and surgical interventions. They to produce a reliable level of sedation and analgesia in the cat, which limited drugs can do. When used alone, there is relatively little change in the dog or cat's pulmonary function; blood gases remain stable although respiratory rate and minute ventilation may decrease after α-2 agonist administration. This class of drug greatly reduces the amount of other drugs (e.g. induction and inhalants) necessary to maintain anesthesia while providing a balanced technique for anesthesia. They are not controlled and reversible should problems arise.
However, the benefits of an α-2 agonist must be weighed against the detrimental effects the drug. There is a profound impact on the cardiovascular system, with an initial peripherally mediated bradycardia secondary to vasoconstriction. This initial effect is followed by a centrally mediated bradycardia and decrease in cardiac output. The reduction in cardiac output is compounded by the effect of concomitantly administered drugs on the cardiovascular system. For example, opioids can also cause bradycardia; using these drugs in combination, although providing synergistic analgesic, may result in a profound bradycardia.
Other body systems are impacted as well. Visceral α-2 receptor upregulation and inhibition of acetylcholine can decrease gastrointestinal motility and increase sphincter tone. Vomiting is a common gastrointestinal side effect as well. Patients receiving α-2 agonists will often have hyperglycemia secondary to inhibition of insulin. Patients may also urinate more after these drugs.
From a practical standpoint, there are other difficulties that result from an incorporation of an α-2 agonist. Patients may actually become more aggressive with α-2 agonist administration, presumably because of the centrally mediated disinhibition that can occur. Obtaining venous access can be more challenging after administration of an α-2 agonist.
Therefore, the benefit of an α-2 agonist for analgesia is dependent on choosing the right case. We will review in this lecture several case examples that may benefit from the use of α-2 agonists and some cases where these drugs are best avoided.
Slingsby, L. S., J. C. Murrell & P. M. Taylor (2010) Combination of dexmedetomidine with buprenorphine enhances the antinociceptive effect to a thermal stimulus in the cat compared with either agent alone. Vet Anaesth Analg, 37, 162-70.