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The opioids are a class of natural, synthetic, or semisynthetic compounds used therapeutically for their analgesic, antitussive, and antidiarrheal effects. This class of alkaloid drugs is derived from the opium poppy, Papaver somniferum, and its properties have been known for thousands of years. Morphine, the class prototype derived from opium, was discovered in 1803. It was named after Morpheus, the Greek god of dreams, as a result of its sedative?hypnotic properties.
Much confusion stems from the similar names used for this class of compounds, such as narcotic, opiate, and opioid. The term narcotic refers to morphine-like drugs having both analgesic and sedative action, whereas opiate refers to morphine-like substances derived from natural sources. The term opioid, coined after the development of synthetic compounds, refers to both natural and synthetic compounds. All 3 terms may be used interchangeably for medical purposes.
All opioids exert their actions through binding to specific opioid receptors located in either the central nervous system (CNS) or the peripheral tissues such as the gastrointestinal (GI) tract. Several receptor subtypes exist, which mediate the various analgesic and adverse effects of opioids. The opioids may easily be classified by their effects on these receptors. Agonists (also known as full agonists) activate receptors; antagonists block receptors; and mixed agonist?antagonists (also known as partial agonists) both activate and block receptors. The agonists may be further classified by the relative strength of their receptor activation, and they may be strong, moderate, or weak.
Clinical Use of Opioids
The most common use of drugs in the opioid class is to provide analgesia for moderate-to-severe pain. Opioids as a class are more efficacious in the relief of constant pain rather than sharp, intermittent pain. In selecting the appropriate agent for a patient, a proper pain assessment should be made, considering the route of administration of the drug (oral versus parenteral), duration of action, ceiling effect (maximal efficacy), duration of therapy, and past experience with opioids. Many practitioners have concerns regarding the development of tolerance and dependence, which should be subjugated in an attempt to make the patient as comfortable as possible. Fixed dosing intervals are more effective in achieving adequate pain relief, rather than as-needed dosing.
Acute Pulmonary Edema
Intravenous morphine is remarkably efficacious in providing relief from dyspnea from pulmonary edema associated with left ventricular failure. Although the exact mechanism for this action is unknown, reduced perception of shortness of breath and an associated anxiolytic effect appear to play a role in this indication.
Opioid doses to achieve an antitussive effect usually are lower than those required for analgesia. Opioids appear to act at different receptors from those needed for analgesia in exerting their antitussive effect, relieving cough with both central and peripheral action. The most commonly used antitussives are dextromethorphan and codeine. Dextromethorphan is available over the counter, due to its lack of analgesic and addictive qualities, and it produces less constipation than does codeine.
The phenylpiperidine subclass of opioids consists of synthetic opiates that can control diarrhea because of their selective GI effects. Agents such as loperamide (available without a prescription) and diphenoxylate reduce peristaltic movements in the bowel and alleviate diarrhea. It is important to remember, however, that infectious causes of diarrhea should be ascertained and treated appropriately. Loperamide is available over the counter, due to its limited ability to cross the blood-brain barrier and its low abuse potential. Diphenoxylate, available by prescription only, is combined with atropine to further reduce its abuse potential.
Parenteral opioids such as fentanyl (80 times more potent than morphine), sufentanyl, and morphine are commonly used in a premedication regimen prior to anesthesia and surgery. These agents are employed because of their sedative, anxiolytic, and analgesic properties. Morphine also is frequently utilized in the epidural route of administration for regional anesthesia.
Adverse Effects of Opioids
Euphoria is a pleasant sensation of floating and of freedom from anxiety that many patients using opioids experience. Tolerance of this effect usually develops with continued use, and some patients may experience dysphoria rather than euphoria. Dysphoria is a state characterized by a sensation of malaise and restlessness.
Drowsiness and mental clouding are frequently reported adverse effects of opioid administration, and sleep patterns may be disrupted. CNS depression may be enhanced with concomitant administration of sedative?hypnotics and should be monitored for closely.
All opioid analgesics are capable of producing clinically significant respiratory depression by inhibition of brainstem respiratory pathways. This effect is dose-related and may be overcome by sensory inputs such as strong painful stimuli. Although this adverse effect should be monitored for closely in patients receiving opioids, it may be reversed by a narcotic antagonist such as naloxone.
Virtually all opioids produce pupillary constriction (miosis), a pharmacologic action to which little or no tolerance develops. This particular adverse effect is valuable as part of the assessment process for opioid overdose.
Nausea and Vomiting
Opioids frequently activate the brainstem chemoreceptor trigger zone, producing nausea and emesis. Tolerance of this adverse effect, like most opioid adverse effects, usually develops, and it may be minimized by having the patient refrain from ambulation.
Constipation is among the few adverse effects that do not diminish over time with chronic opioid use. Therefore, patients requiring longterm treatment with opioids require a bowel regimen with stimulant laxatives taken on a scheduled basis to prevent this complication.
Tolerance of the analgesic, euphoric, and respiratory-depressant effects of opioids may begin with the first dose of a particular agent. Clinically significant tolerance, however, usually does not develop until after 2 to 3 weeks of therapeutic dosing. This phenomenon typically occurs most readily when large doses are given over short time periods, and it differs widely, depending on the agent in use. Cross-tolerance also develops, whereby a patient tolerant to morphine, for example, is tolerant of other agents in the opioid class.
When opioids are discontinued in tolerant patients, a withdrawal or abstinence syndrome occurs. Signs and symptoms of this syndrome include rhinorrhea, lacrimation, yawning, chills, hyperventilation, myalgias, and other effects. These symptoms and their intensity depend largely on the degree of physiologic dependence that has developed. Chronically treated patients are most at risk.
The euphoria produced by opioids may lead to their compulsive use by some patients. Despite this risk, adequate pain relief should not be withheld simply because opioids may produce this effect. To minimize the potential for psychological addiction, clinicians should establish appropriate therapeutic goals, with frequent reevaluation and monitoring of analgesic needs.
The opioids are a clinically significant group of compounds that provide benefits in many therapeutic areas. A thorough understanding of their effects, both clinical and adverse, is required to employ them in an effort to improve patient outcomes. Pharmacists have a pivotal role to play in assisting practitioners in the proper selection and use of opioids to achieve the best results for patients.
LT Newman is a senior assistant pharmacy officer with the US Public Health Service/Federal Bureau of Prisons. He is currently based at Springfield US Medical Center for Federal Prisoners, Springfield, Mo.
The opinions expressed in this article are those of the author and do not necessarily reflect the views of the US Public Health Service or the Federal Bureau of Prisons.