Synthetic opioids remain powerful and perhaps one of the most useful tools for managing pain and avoiding a maladaptive pain state in both human and veterinary patients. However, the single most common reason cited by veterinarians for avoiding the use of opioid analgesia is a fear of adverse effects.1 These concerns can be successfully addressed and usually avoided by understanding how these drugs work within the peripheral and central nervous system, developing opioid-sparing strategies, and knowing how to promptly recognize and treat adverse effects should they appear.
Mark E. Epstein
HOW OPIOIDS WORK
Activation of mu-opioid receptors inhibits presynaptic release and postsynaptic response to excitatory neurotransmitters, closing calcium channels and opening potassium channels. The result is greatly impeded pain transmission.
We've recently discovered that glial cells, once thought to play only a minor supporting role in the spinal cord, are actually highly active in the pain process—enlarging, migrating, and wrapping themselves around nociceptor synapses in the face of peripheral injury.2 They possess many types of receptors including opioid receptors. Therefore, they have the potential to both create and sustain a pain state and can result in a seemingly paradoxical hyperalgesia in some patients treated with opioids.3
Practitioners have three general categories to choose from—pure mu agonists; partial mu agonists and agonist-antagonists; and mu antagonists. Below is an overview of the indications for each.
Pure mu agonists: "Strong" opioids
Morphine. Federally regulated since World War I, morphine has lost none of its potency or utility in the intervening near 100 years. It has no ceiling effect on analgesia, histamine release, or respiratory depression, meaning that higher dosing can increase the analgesic effect as well as respiratory depression. It consistently results in transient nausea and vomiting (especially at low doses given subcutaneously or intramuscularly to nonpainful patients, for example, as a premedicant), which for many clinicians is actually a persuasive reason for its use preoperatively. Since cats are unable to produce the primary M6G analgesic metabolite,4 morphine may not be ideal for use in this species; however, many clinicians report satisfactory use of morphine in cats (perhaps there are other mu-agonist metabolites in this species).
Oxymorphone and hydromorphone. These two opioids are shorter-acting than morphine, a feature some clinicians think makes them more versatile than morphine. They do not elicit histamine release, making them superior to morphine for trauma patients. Nausea, while still predictable, seems to be somewhat milder than that elicited by morphine. While all opioids can induce a transient hyperthermia in cats, hydromorphone appears to be implicated more often than other pure mu agonists.5
Methadone. Easily available and commonly used in Europe, injectable methadone may become an attractive alternative to other pure mu agonists here in the United States. It elicits minimal nausea and no histamine release, has NMDA-R blocking activity,6 and is nicely sedating in addition to its analgesic effects. Its effectiveness has been demonstrated in dogs and cats.7,8
Fentanyl. This short-acting mu agonist is far more potent than morphine. It is most often administered as an intravenous constant-rate infusion in veterinary medicine, and its short action allows for a great deal of flexibility in managing a patient since the rate can be fine-tuned based on patient response and needs. The transdermal patch (Duragesic—Janssen Pharmaceutica) formulation is less popular in veterinary medicine than it once was (it still is commonly prescribed for its labeled indication in humans for breakthrough cancer pain) because of the highly unpredictable dosing and effects that are based on numerous variables such as species, body condition score, and body temperature, as well as where and how (and how well) the patch is placed. Additionally, there are serious public health concerns surrounding accidental contact or ingestion by people, especially infants and children—a number of deaths have been recorded since this product has been on the market.
Myths about opioid use