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  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. Opioids are analgesics. Unlike local anesthetics and the anti-inflammatory inhibitors of cyclooxygenase, they alter the perception of pain as a noxious entity.

  2. The “classical” pharmacologic effects of morphine, such as analgesia and ventilatory depression, are mediated by μ receptors. κ and δ receptors are more important in mediating the effects of some endogenous opioids.

  3. Opioids relieve prolonged, burning pain more effectively than the sharp pain of an incision. Neuropathic pain can be resistant to opioid treatment. Intraoperative opioids can reduce or abolish autonomic and somatic responses to surgical stimuli.

  4. Opioids produce drowsiness and difficulty concentrating. They do not usually produce anterograde amnesia. Doses sufficient to produce apnea and profound analgesia do not reliably produce unconsciousness.

  5. Opioids produce dose-related depression of the ventilatory response to CO2 as well as to hypoxia. A decrease in ventilatory rate is not a sensitive indicator of opioid effect. Sleep will further potentiate the ventilatory depression. Equianalgesic doses of all full agonists produce equivalent amounts of ventilatory depression.

  6. Opioids suppress cough by depressing putative cough centers in the medulla. This effect is not mediated through classical opioid receptors. Dextrorotatory isomers of opioid analgesics retain antitussive activity.

  7. Opioids produce complex effects on vomiting centers in the medulla. There is direct stimulation of the chemoreceptor trigger zone. The emetic effects are potentiated by stimulation of the vestibular apparatus.

  8. Hypertonus of skeletal muscle may be produced by large intravenous doses of opioids, especially fentanyl and its derivatives. “Lead pipe” muscle rigidity may prevent mechanical ventilation. The primary etiology is supraglottic obstruction from constriction of laryngeal and pharyngeal muscles.

  9. Morphine and meperidine produce a nonimmunologic release of histamine from tissue mast cells, often mistaken for allergy. There may be transient hypotension.

  10. Opioids decrease propulsive movements in the gastrointestinal tract while increasing sphincter tone. Chronic administration usually requires laxatives or stool softeners to treat constipation.

  11. When tolerance to an opioid occurs, there is simultaneous cross-tolerance to other agonists. Tolerance develops to the depressant effects (analgesia, ventilatory depression, euphoria), but less so to the stimulant effects (constipation, pupillary constriction).

  12. Physical dependence is not the same thing as psychological dependence or addiction that includes compulsive drug-seeking behavior. The risk of addiction can be minimized by careful medical management.

  13. Morphine is the least lipophilic of the opioids. It penetrates biologic membranes more slowly than lipophilic opioids. In spite of its rapid distribution and elimination from plasma, changes in brain concentration are small and delayed, and its onset and offset are slow.

  14. Meperidine or its metabolites inhibit SERT (the presynaptic serotonin γ-aminobutyric acid [GABA] family transporter) and may produce serotonin syndrome, especially in patients taking monoamine oxidase inhibitors. A metabolite has proconvulsant activity.

  15. Methadone is long lasting due to its long terminal half-life. It has high oral bioavailability (approximately 80%). Repeated ...

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