Opioids (Proceedings)


Opioids (Proceedings)

Aug 01, 2011

Even in the modern day, opioids remain the cornerstone of analgesia. Aesop's fables gave rise to the saying that "Familiarity breeds contempt"; these drugs are often underappreciated because of their long history as analgesics. Opioids may not be "novel" but they are critical to pain relief and a strategy that our patients benefit from. Opioids are have a high margin of safety and efficacy, and are reversible should the need arise. This lecture will review pertinent information about opioids, and case examples where the use of opioids is beneficial.

The poppy plant, from which opium (and thus morphine) is derived, was known to have analgesic properties as far back as 5000 BC. However, morphine (the "prototype" opioid) was not actually isolated until the early 1800s—which was the same time an interest in general anesthesia was rising, to facilitate the practice of surgery. However, it was not until the late 1980s when Wall proposed the benefit of adding analgesia to reduce pain before the painful or noxious sensation began. Indeed, evidence suggests that pain in the early postoperative period is a predictor of long-term pain (Katz et al. 1996). After much investigation, it is believed that it is the processing of pain at the level of the spinal cord that heavily contributes to the long-term response of the body. Opioids, which work at the dorsal horn of the spinal cord as well as supraspinally, can modulate this pain transmission (although unlike local anesthetics they cannot prevent it). In addition to analgesia, opioids can contribute to sedation, a reduction in anesthetic drugs necessary, and cardiovascular stability of patients who are receiving opioids prior to anesthesia.

Because the effects of opioids are related to the receptor the opioid targets, a brief review of opioid receptors is warranted. Our primary target is the OP3 or μ receptor, as this receptor is primarily responsible for the analgesic effects of opioids. Drugs that target this receptor include fentanyl, hydromorphone, meperidine, methadone, morphine, remifentanil, and tramadol. Drugs that target the μ receptor have a perfect efficacy and are all as potent, and potentially quite a bit more potent, than morphine. Buprenorphine, which works at the μ receptor, is more potent but less efficacious than morphine. Some opioids also target the OP2 or κ receptors (butrophanol, pentazocine, nalbuphine). While these drugs may be more potent than morphine, they are not as efficacious as morphine. In the cat, there is some evidence that butrophanol may provide acceptable analgesia of longer duration than in the dog for procedures that are not highly invasive. The last receptor class is OP1, or the d receptor, which dose not appear to have much to offer in regards to acute analgesia. However, there may be benefits for chronic pain (Gaveriaux-Ruff et al. 2011).

In addition to opioids providing analgesia alone, there is a growing body of research suggesting that opioids, when combined with other analgesics, may provide even better analgesia than when administered alone (multimodal analgesia). For example, recent work by Slingsby suggests that in a research model, cats given a combination of 10 mcg/kg buprenorphine with 20 mcg/kg of dexmedetomidine had better analgesia than if either drug were administered alone—with analgesia that was earlier in onset and with a longer duration (Slingsby, Murrell and Taylor 2010). A similar synergism has been demonstrated in veterinary species between non-steroidal anti-inflammatory drugs (NSAIDs) and opioids.

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