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INTRODUCTION

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Opioids refers broadly to all compounds related to opium that possess analgesic and sedative properties. Opiate describes the opioid alkaloids found naturally in the opium poppy plant, Papaver somniferum. The term narcotic refers to a broader group of agents, predominantly used by law enforcement to designate a variety of controlled substances with abuse or addictive potential; use of this term in medical practice is discouraged.

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Opioid abuse is a significant public health issue in the United States with a dramatic increase in prescription opioid use and abuse in the past 10 years.1,2 Opioids most frequently involved in reported toxic drug exposures were, in order of number of cases recorded, tramadol, oxycodone, methadone, morphine, buprenorphine, and hydrocodone.3 Deaths were primarily associated with exposure to methadone, oxycodone, and morphine. The majority of prescription opioid overdose deaths were associated with diversion, doctor shopping, and nonmedical use.

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PHARMACOLOGY

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Opioids modulate nociception in the terminals of afferent nerves in the CNS, peripheral nervous system, and GI tract. Opioids are agonists at the three primary opioid receptors: μ (mu), κ (kappa), and δ (delta). Opioid receptors are similar to other G protein–coupled receptors; they are transmembrane proteins that undergo conformational change when activated by external molecules, and this change then alters some aspect of intracellular function. Opioid receptors vary widely in morphology and distribution. Also, the specificity and affinity of an opioid for a particular receptor are variable. For example, tramadol possesses 1/6000 the affinity of morphine at the μ-receptor site.

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Stimulation of the μ-receptors results in analgesia, sedation, miosis, respiratory depression, cough suppression, euphoria, and decreased GI motility. Stimulation of κ-receptors results in weaker analgesia, sedation, miosis, decreased intestinal motility, dysphoria, and hallucinations. Stimulation of the δ-receptors results in some analgesia and antidepressant effect. All currently available opioid agonists possess μ-receptor activity and result in some degree of respiratory depression.

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There is interplay between opioid receptors and other transmembrane receptors found in the nervous system. One example is that opioid binding to μ-receptors in the nucleus accumbens results in the localized release of dopamine (the "dopamine pleasure pathway"). A second example is that the analgesic effect of morphine is enhanced in the presence of N-methyl-d-aspartate receptor blockers such as amantadine. A third example is the induction of mast cell histamine release by morphine and meperidine.

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Opioids can be categorized as naturally occurring compounds (termed opiates), chemical modifications of natural compounds (semisynthetic), and completely artificial compounds (synthetic) (Table 186-1). Some opioids are agonists at all opioid receptors (e.g., morphine and hydromorphone), whereas others are partial agonists–antagonists (e.g., pentazocine, butorphanol, and nalbuphine) at the opioid receptors.

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Table Graphic Jump Location
TABLE 186-1Classification and Characteristics of Major Pharmaceutical Opioids

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