Oxycodone: Mechanisms of Action, Clinical Uses and Adverse Effects
Oxycodone is a semisynthetic opioid drug with analgesic properties.1 Oxycodone is manufactured by modifying the chemical thebaine, an organic chemical found in opium.2 It is the active ingredient in prescription pain medications such as Percocet, Percodan, Tylox and OxyContin, which are formulated through combinations with other pain relievers such as aspirin.1 Oxycodone was first developed in Germany in 1916, and it first came to the United States in 1939.3 In 1996, when Purdue Pharma began manufacturing OxyContin in the U.S., oxycodone became more widely used (and abused).3 Because oxycodone is an active ingredient in several pain medications, anesthesia providers should have thorough knowledge of its biological mechanisms, clinical applications and side effects.
The molecular formula for oxycodone is C18H21NO4.4 Oxycodone is a μ-opioid and κ-opioid receptor agonist.5 Through binding at both of these receptors, oxycodone inhibits neuronal activity4 and exhibits antinociceptive (i.e., pain-relieving) effects.5 It binds to areas in the cortex and other regions that have effects not relating to analgesia, such as the respiratory center in the brainstem, cough center in the medulla oblongata, muscles of the pupils, gastrointestinal tract, cardiovascular system, endocrine system and immune system.4 The lipid solubility of oxycodone is similar to that of morphine, and protein binding is low (i.e., 38 percent to 45 percent).5 Oxycodone’s duration of action depends on its formulation, ranging from three to four hours to 12 hours.6 Because it undergoes low first-pass metabolism, the oral bioavailability of oxycodone is better than morphine, ranging from 60 to 87 percent.7 Thus, it is almost twice as potent as morphine.8 It is metabolized mainly in the liver by CYP3A4 and CYP2D6 enzymes to the active metabolite oxymorphone, which is three times more potent than morphine.7 Another metabolite of oxycodone is noroxycodone, which has weak µ-opioid receptor activity compared with oxycodone or oxymorphone.7 Oxycodone and its metabolites are excreted in the urine, with less than 10 percent of oxycodone excreted unchanged.7 Women eliminate oxycodone 25 percent more slowly than do men.5 Overall, oxycodone and its metabolites exert analgesic effects through actions on opioid receptors.
Oxycodone can be used in a variety of clinical settings. Oxycodone products can be administered intramuscularly, intravenously, subcutaneously, rectally or orally through pills and tablets.9 Parenteral (i.e., not oral) oxycodone is not available in the United States.10 In the U.S., oxycodone is currently used in a controlled-release preparation for cancer-related and chronic non-malignant pain, as well as in an immediate-release preparation for acute or breakthrough pain.11 Its immediate and sustained-release formulations make it useful for moderate to severe postoperative pain.12 In other countries, intravenous oxycodone can be administered during the preoperative period to induce sedation and prevent perioperative pain.13 Oxycodone has clinical uses that are similar to those of other opioid drugs; however, its parenteral applications are not available in the U.S.
The side effects of oxycodone are similar to those of other opioids.5 Oxycodone may cause drowsiness, confusion, lightheadedness, nausea, vomiting, pruritus (itching), sweating, urinary retention and constipation.14 The incidence of constipation is more than with morphine, but there is a relatively decreased incidence of nausea.5 More severe consequences of oxycodone use may include changes in pulse, respiration and blood pressure; seizures; pupil constriction; loss of consciousness; or coma and/or death.14,15 Compared to other opioid drugs, oxycodone has an increased potential for abuse and dependence.16 Drugs made from oxycodone, such as OxyContin, can be crushed up and used intranasally or intravenously to achieve a “high.”17 Providers should be careful when prescribing oxycodone given the addictive properties, adverse effects and overdose potential of oxycodone-containing formulations.
Oxycodone is a semisynthetic analgesic drug that acts as a μ-opioid and κ-opioid receptor agonist, thus inhibiting the body’s sense of pain. The metabolism of oxycodone in the liver creates active metabolites, which have an additional analgesic effect. Oxycodone is available in immediate-release and long-acting formulations, giving it clinical applications that include both acute and chronic pain. The side effects of oxycodone, such as drowsiness, nausea, vomiting, itching, sweating and constipation, are similar to those of other opioid drugs. Oxycodone overdose can have severe consequences such as respiratory depression and death. Due to the widespread abuse of oxycodone-based drugs such as OxyContin, anesthesia providers should carefully consider prescribing oxycodone.
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