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.
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 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.
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.
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.
Common ADRs include: nausea and vomiting, drowsiness, dizziness, headache, Orthostatic hypotension, itch, dry mouth, Miosis, urinary retention, and constipation. (Rossi, 2005)
Infrequent ADRs include: dose-related respiratory depression (see below), confusion, hallucinations, Delirium, Urticaria, Hypothermia, Bradycardia/Tachycardia, ureteric or biliary spasm, muscle rigidity, myoclonus (with high doses), and flushing (due to histamine release, except fentanyl and remifentanil). (Rossi, 2005).
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.
Chronic use of opioids may result in serious cases of Constipation, which may progress to Bowel obstruction, Fecal impaction, or paralytic ileus. Because these conditions may require surgical intervention, stimulant laxatives are generally given as an adjunct to prevent these complications. Physiological tolerance does not develop with regard to constipation. It should be noted that in some therapeutic regimens (such as those aimed at treating diarrhea), mild constipation would be a desired effect and hence laxatives would not be given.
It has been observed that both therapeutic and chronic use of opioids can compromise the function of the Immune system. Opioids decrease the proliferation of Macrophage progenitor cells and lymphocytes, and affect cell differentiation. (Roy & Loh, 1996) Opioids may also inhibit leukocyte migration.
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)
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.