An opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. There are four broad classes of opioids: endogenous opioid peptides, produced in the body; opium alkaloids, such as morphine (the prototypical opioid) and codeine; semi-synthetic opioids such as heroin and oxycodone; and fully synthetic opioids such as pethidine and methadone that have structures unrelated to the opium alkaloids.
Although the term opiate is often used to refer to all opium-like drugs, it is more properly limited to the natural opium alkaloids and the semi-synthetics derived from them.
Main article: opioid receptor
There are at least three major classes of opioid receptors: μ, κ and δ. These are all G-protein coupled receptors acting on GABAergic neurotransmission . The μ receptor (the μ represents morphine) is perhaps the most important - being responsible for most of the analgesic and other major pharmacological effects as well as many of the adverse effects of opioids.
Opioid overdose can be rapidly reversed with any of several opioid antagonists such as naloxone. These competitive antagonists are drugs that bind to the μ-opioid receptors with higher affinity than agonists but do not activate them. This displaces the agonist, attenuating and/or reversing the agonist effects.
Uses of opioids
Opioids are widely used in medicine as strong analgesics (pain relievers). Despite extensive research, to date no analgesics have been found that are more effective for severe pain. One of the advantages of opioids is that there is no upper limit to the dosage and the achievable pain relief as long as the dose is increased gradually to allow tolerance to develop to adverse effects (especially respiratory depression).
The main clinical indications of opioids include (Rossi, 2004):
Opioids have long been used to treat acute pain (such as post-operative pain). They have also found to be invaluable in palliative care to alleviate the severe, chronic, disabling pain of terminal conditions such as cancer. Very high doses are often required in palliation to improve the patients' terminal quality-of-life.
In recent years there has been an increased use of opioids in the management of non-malignant chronic pain. While this trend is still somewhat controversial in some circles, due to issues of dependence, the emerging medical consensus is that most chronic pain patients can safely use opioids for years with a minimal risk of addiction or toxicity and that the overall increase in quality of life outweighs any adverse effects of opioid-use.
As recently as the early 20th century, opioids were administered by doctors to treat severe depression and other psychiatric disorders. The practice was discontinued because of the dependence-producing nature of opioids.
Possible future use
Limited evidence in the past decade shows promise for opioid-derivatives in the treatment of psychiatric conditions such as obsessive compulsive disorder.
Some opioids are widely abused for their euphoria-producing properties when administered orally, intravenously, intranasally, or when smoked. The euphoria is one of the principal bases behind the development of psychological dependence. Tolerance rapidly develops to this effect, and rapid dose escalations are required by users seeking to achieve the euphoric state. A relatively small dose of a fast-acting opioid may produce intense euphoria in an "opioid naive" user, but once tolerance develops even very large doses may produce none at all. Opioids also block pain, both physical and emotional. Users come to rely on this ability to block out unwanted feelings, and escape reality.
Due to the Harrison Narcotics Tax Act of 1914 and subsequential international laws and treaties, the recreational use of opioids has been greatly constricted and criminalised. Many feel that this is unduly stigmatizing. They point out that scientifically, the relative addictiveness of opioids are on par with alcohol, and traditionally cultures have learned to use them responsibly, keeping abuse rates below that of alcohol, and sometimes even banning alcohol in favor of opium. Physically, long term use of some opioids actually results in less harm to the body than that of alcohol.
Synthetic opioids have similar action to the natural opiates, which metabolize to morphine (named after Morpheus, the Greek god of dreams), which can produce a state of sedation that lies of the edge of sleep and waking known as the nod. The nod is a sort of drug induced daydream where the user alternates between drowsiness and wakefulness. This less publicized altered state of mind is more traditionally desired than the rush of shooting up heroin, and is more reminiscent of oriental opium dens.
Ludibund (or "recreational") users of opioids are generally known as chippers (a term also used to refer to the occasional tobacco smoker), to distinguish them from the hardcore daily user.
Opioids are associated with a range of adverse drug reactions (ADRs) - mostly associated with their pharmacological action at opioid receptors.
Common ADRs include: nausea and vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention, and constipation. (Rossi, 2004)
Infrequent ADRs include: confusion, hallucinations, delirium, urticaria, itch, hypothermia, bradycardia/tachycardia, raised intracranial pressure, ureteric or biliary spasm, muscle rigidity, and flushing. (Rossi, 2004)
The most severe and serious ADR associated with opioid-use is respiratory depression. Although tolerance develops rapidly, respiratory depression is the mechanism behind the fatal consequences of overdose.
Tolerance can be detected within 12-24 hours of the administration of morphine (Rang et al., 2003), and similarly for other opioid agonists. Tolerance results in the necessity for increasing the dose over time to achieve the desired clinical effect.
Tolerance appears to develop first to the analgesic, sedative, emetic, euphoric and respiratory depressive effects of opioids. The miotic and constipating effects tend to be relatively resistant to the development of tolerance. (Rang et al., 2003)
Dependence and withdrawal issues
Regular use of an opioid for any reason rapidly induces physical dependence, characterized by a highly unpleasant withdrawal syndrome when the drug is discontinued or rapidly decreased in dosage, or when an antagonist is administered. The acute withdrawal syndrome generally consists of signs and symptoms opposite to those of the drug when initially administered: severe dysphoria, anxiety, eye tearing, a runny nose, goose bumps, cramps and deep pains are common. The speed and severity of withdrawal depends on the half-life of the opioid - heroin withdrawal occurs more quickly and is more severe than methadone withdrawal, but methadone withdrawal takes longer. The acute withdrawal phase is often followed by a protracted phase of depression and insomnia that can last for months.
Physical dependence is completely distinct from and does not imply psychological addiction, defined as uncontrolled drug use despite harm. However, physical dependence can certainly aggravate psychological addiction when it occurs.
Withdrawal symptoms can be greatly lessened by slowly tapering the dose over days or weeks, sometimes after switching to a long-acting opioid such as methadone. The symptoms of opioid withdrawal can also be treated with other medications, such as clonidine for sympathetic hyperactivity and a benzodiazepine for anxiety and insomnia.
"Rapid detox" is a relatively new technique that uses opioid antagonists to cause acute withdrawal while the patient is under general anesthesia to eliminate the otherwise extreme discomfort. This procedure has attracted considerable controversy due to its high cost and risk; several patients have died during the procedure. Many pain specialists consider the procedure unnecessary, and addiction specialists criticize it for doing nothing to keep an addict from relapsing into opioid abuse after the procedure is complete. Rapid detox also does not alleviate the protracted withdrawal syndrome that lasts for weeks or months after the acute phase.
Although physical dependence is nearly universal among those who use opioids regularly, true addiction is actually quite rare even when large amounts of opioids are used over long periods of time to treat chronic pain under the close supervision of a doctor. This is thought to be due to the rapid development of tolerance to the euphorigenic properties of opioids; without euphoria, only the unpleasant side effects (such as bowel dysfunction) remain so there is no motivation to take more than is needed to manage pain.
Examples of opioids
Opioid-peptides that are produced in the body:
Phenanthrenes naturally occurring in opium:
- levomethadyl acetate hydrochloride (LAAM)