Opioids are a group of natural derivatives or synthetic relatives of opium, which is extracted from the exudate of seedpods
of the opium poppy, Papaver somniferum. The poppy plant appears to have been cultivated in ancient civilizations, like those of Persia, Egypt and Mesopotamia, and
the first known written reference to the poppy appears in 4,000 BC (from 'A Brief History of Opium' at http://opiates.net/).
Both the recreational and the medical attributes of opioids were well known throughout history and the compounds were
widely used in all levels of society and opium was easily obtained from the local druggist. Crude opium was the main form
of the drug until 1805 when morphine was isolated from opium by a German pharmacist, who named it morphium - after Morpheus,
the Greek god of dreams (from 'A Brief History of Opium' at http://opiates.net/). Today there are numerous forms of the drug and numerous medical applications. There is also extensive interest in the drug
class and a 2011 PubMed search of 'opioids' yielded 110,814 hits.
Opioids bind to specific opioid receptors that are located primarily in the central and peripheral nervous systems, although
locations exist in other tissues (eg, synovium). The three principal opioid receptors are mu, kappa and delta, and numerous
other minor receptors and subreceptors have been identified. Opioids primarily bind to presynaptic receptors and cause a decrease
in the release of excitatory neurotransmitters.
Opioids are traditionally (and loosely) classified as 'full agonists', 'partial agonists', 'agonists-antagonists' and 'antagonists',
depending on their activity at the mu opioid receptor. Full agonists bind to and activate both the mu and kappa receptors
and commonly used drugs in this category include morphine, hydromorphone, fentanyl (and the fentanyl derivatives), methadone
and codeine. Partial agonists bind to, but only partially activate, the mu receptor and can have varying activity at the kappa
receptor. The drug most commonly used in veterinary medicine that fits this category is buprenorphine. Some experts consider
buprenorphine to be an agonist-antagonist but most feel that it better fits the partial agonist category. The classically
used agonist-antagonist is butorphanol, which is an agonist at the kappa receptor but an antagonist at the mu receptor. Pentazocine
and nalbuphine are also agonist-antagonists. Finally, we have the antagonists, naloxone and naltrexone. Antagonists bind to
the receptor but do not activate it. The binding blocks the binding of the drugs that would activate the receptor (the agonists),
thereby eliminating the effects of those drugs.
Opioids are a versatile class of drugs that can be used systemically (IV, IM, SQ, PO), in the epidural or intrathecal space
and in the articular space. Opioids can be used to treat both acute (Table 1) and chronic (Table 2) pain. The primary medically
positive effect of opioids is analgesia, although euphoria may also be considered a benefit in certain patients. The primary
medically adverse effects of the opioids include nausea, vomiting, constipation, slowing of GI motility, dysphoria, pruritis
and respiratory depression. The actual incidence of many of these side effects is highly overstated and the benefits of the
opioid class should be weighed against the potential for the adverse effects.