Chapter 42

1. An opioid is any natural or synthetic compound that has effects similar to those of morphine or that acts as an antagonist at the same receptors to which morphine binds.

2. Because opioid agonists relieve pain, they are classified as analgesics. In contrast to the local anesthetics (which interrupt the transmission of all nerve impulses, including pain) and the anti-inflammatory analgesics such as aspirin (which decrease some of the pathologic processes leading to pain), the opioid analgesics act primarily to alter the perception of pain as a noxious entity.

3. The “classic” pharmacologic effects of morphine, such as analgesia and ventilatory depression, are mediated by μ receptors. The κ receptor shares a number of effects with the μ receptor, including analgesia, sedation, and ventilatory depression. The δ receptor is responsible for mediating some of the analgesic effects of the endogenous opioid peptides, especially in the spinal cord.

4. All opioid receptors are G-protein coupled receptors. The actions of both μ and δ agonists result in overall neuronal depression, and they share several signal transduction mechanisms, including inhibition of adenylyl cyclase, activation of K+ currents, and suppression of Ca2+ currents.

5. Five families of endogenous opioid peptides bind to the various opioid receptors. Although some of these peptides undoubtedly function in nociceptive pathways, they also appear to play fundamental roles in processes like thermoregulation and hormone release, as well as gastrointestinal and cardiovascular control.

6. The most widely used opioid analgesics are the pure agonists that are relatively selective for μ-opioid receptors. Unlike the volatile anesthetics, opioid agonists produce a group of highly specific depressant and stimulant effects by acting at discrete sites within the central nervous system.

7. Opioid analgesic effects result from actions at several different levels of the neuraxis. Patients given morphine will typically report that pain is still present, but the intensity is decreased and it no longer bothers them as much. Sufficient doses of opioids will relieve almost any pain, although some types of pain are typically more responsive than others. Prolonged, burning pain, for example, is more effectively blunted than the brief, sharp pain of an incision. Neuropathic pain (eg, pain of nerve root compression) can be very resistant to opioid treatment. Intraoperatively the opioids can produce sufficient analgesia to reduce or abolish autonomic and somatic responses to surgical stimuli.

8. In usual analgesic doses, morphine-like drugs may produce drowsiness, feelings of heaviness, and difficulty concentrating. Unlike benzodiazepines, opioids do not usually produce anterograde amnesia. Doses of opioids that are sufficient to produce apnea and profound analgesia do not reliably produce unconsciousness in healthy individuals.

9. True seizures have been reported after repeated doses of meperidine because its major metabolite, normeperidine, is a potent convulsant.

10. Opioids produce a dose-related depression of the ventilatory response to CO2 by a direct effect on ventilatory centers in the medulla. Morphine also blunts the response to hypoxia. It is important to remember that a decrease in ventilatory rate is not a very sensitive indicator of opioid effect. A patient's drive ...

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