The term opioids refers broadly to all compounds
related to opium that possess analgesic and sedative properties.
The term narcotic refers to a broader group of
agents and is predominantly used by law enforcement to designate
a variety of controlled substances with abuse or addictive potential.
Because narcotic is not descriptive of a unique
drug class, use of this term in the practice of medicine is discouraged.
Opioid abuse is a significant public health issue in the U.S.
Between 2004 and 2006, ED visits associated with opioid abuse or
misuse increased 43%.1 The opioids most
commonly reported to be involved are, in order of frequency, heroin,
oxycodone, hydrocodone, and methadone.1 Between
1999 and 2002, there was a 91% increase in the number of
deaths attributed to poisoning from prescription opioids.2 The
majority of prescription opioid overdose deaths were associated
with diversion, doctor shopping, and nonmedical use of these drugs.3 During
2008, the American Association of Poison Control Centers received
reports of 126,456 exposures to opioids; 84,861 were multidrug exposures
that included opioids and 41,595 were single-drug exposures to an
opioid. There were 401 fatalities that mentioned an opioid and 66
of these fatalities associated with only an opioid.4
Opioids modulate nociception in the terminals of afferent nerves
in the central nervous system, 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 in that
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 is variable. For example, tramadol possesses 1/6000
the affinity of morphine at the μ-receptor site.
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 analgesia, although less than does stimulation of the μ-receptors,
and produces some antidepressant effect, but the clinical role of δ-receptor
stimulation is largely unknown. All currently available opioid agonists
have activity at the μ-receptor and result in some
degree of respiratory depression.
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.
Opioids can be categorized as naturally occurring compounds (termed opiates),
chemical modifications of natural compounds ...