Oxycodone
Oxycodone, sold under the brand names Roxicodone and OxyContin among others, is a semi-synthetic opioid used medically for the treatment of moderate to severe pain. It is a highly addictive and commonly abused drug. It is usually taken orally, and is available in immediate-release and controlled-release formulations. Onset of pain relief typically begins within fifteen minutes and lasts for up to six hours with the immediate-release formulation. In the United Kingdom, it is available by injection. Combination products are also available with paracetamol, ibuprofen, naloxone, naltrexone, and aspirin.
Common side effects include euphoria, constipation, nausea, vomiting, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating. Side effects may also include addiction and dependence, substance abuse, irritability, depression or mania, delirium, hallucinations, hypoventilation, gastroparesis, bradycardia, and hypotension. Those allergic to codeine may also be allergic to oxycodone. Use of oxycodone in early pregnancy appears relatively safe. Opioid withdrawal may occur if rapidly stopped. Oxycodone acts by activating the μ-opioid receptor. When taken by mouth, it has roughly 1.5 times the effect of the equivalent amount of morphine.
Oxycodone was originally produced from the opium poppy opiate alkaloid thebaine in 1916 in Germany. One year later, it was used medically for the first time in Germany. Oxycodone is a therapeutic alternative on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 49th most commonly prescribed medication in the United States, with more than 13million prescriptions. A number of abuse-deterrent formulations are available, such as in combination with naloxone or naltrexone.
Medical uses
Oxycodone is used for managing moderate to severe acute or chronic pain when other treatments are not sufficient. Oxycodone improves quality of life in certain types of pain. Numerous studies have been completed, and the appropriate use of this compound does improve the quality of life of patients with long term chronic pain syndromes.Oxycodone can be taken in an immediate-release form or twice daily with extended-release forms and both forms are Extended-release forms of oxycodone and are used for around-the-clock treatment of pain worldwide, are not to be used on an "as needed" basis, while other forms such as the immediate-release forms are indicated as to be used as rescue medications in the treatment of pain. There are many forms of the drug that are recognized by the Food and Drug Administration, National Health Service and NHS Scotland to be used for various indications.
Oxycodone is available as a controlled-release tablet. A 2006 review found that controlled-release oxycodone is comparable to immediate-release oxycodone, morphine, and hydromorphone in management of moderate to severe cancer pain, with fewer side effects than morphine. The author concluded that the controlled-release form is a valid alternative to morphine and a first-line treatment for cancer pain. In 2014, the European Association for Palliative Care recommended oxycodone by mouth as a second-line alternative to morphine by mouth for cancer pain.
In children between 11 and 16, the extended-release formulation is FDA-approved for the relief of cancer pain, trauma pain, or pain due to major surgery – this provides an alternative to Duragesic, the only other extended-release opioid analgesic approved for children.
Oxycodone, in its extended-release form or in combination with naloxone, is sometimes used off-label in the treatment of severe and refractory restless legs syndrome.
Available forms
Oxycodone is available in a variety of formulations for by mouth or under the tongue:- Immediate-release oxycodone
- Controlled-release oxycodone – 10–12 hour duration
- Oxycodone tamper-resistant
- Immediate-release oxycodone with paracetamol
- Immediate-release oxycodone with aspirin
- Immediate-release oxycodone with ibuprofen
- Controlled-release oxycodone with naloxone – 10–12 hour duration
- Controlled-release oxycodone with naltrexone – 10–12 hour duration
Side effects
The most common side effects of oxycodone include delayed gastric emptying, euphoria, anxiolysis, feelings of relaxation, and respiratory depression. Common side effects of oxycodone include constipation, nausea, vomiting, drowsiness, dizziness, itching, dry mouth, and sweating. Less common side effects include loss of appetite, nervousness, abdominal pain, diarrhea, urinary retention, dyspnea, and hiccups.Most side effects generally become less intense over time, although issues related to constipation are likely to continue for the duration of use. Chronic use of oxycodone and the associated constipation issues can become severe, and have been implicated in life-threatening bowel perforations. A number of specific medications including naloxegol have been developed to address opioid induced constipation.
Oxycodone in combination with naloxone in managed-release tablets has been formulated to both deter abuse and reduce opioid-induced constipation.
Dependence and withdrawal
The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent and discontinues oxycodone abruptly. Medically, when the drug has been taken regularly over an extended period, it is withdrawn gradually rather than abruptly. People who regularly use oxycodone recreationally or at higher than prescribed doses are at even higher risk of severe withdrawal symptoms. The symptoms of oxycodone withdrawal, as with other opioids, may include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness, fevers, and other flu-like symptoms".Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy.
Hormone levels
As with other opioids, chronic use of oxycodone can often cause concurrent hypogonadism.Overdose
In high doses, overdoses, or in some persons not tolerant to opioids, oxycodone can cause shallow breathing, slowed heart rate, cold/clammy skin, pauses in breathing, low blood pressure, constricted pupils, circulatory collapse, respiratory arrest, and death.In 2011, it was the leading cause of drug-related deaths in the U.S. However, from 2012 onwards, heroin and fentanyl have become more common causes of drug-related deaths.
Interactions
Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6. Therefore, its clearance can be altered by inhibitors and inducers of these enzymes, increasing and decreasing half-life, respectively. Natural genetic variation in these enzymes can also influence the clearance of oxycodone, which may be related to the wide inter-individual variability in its half-life and potency.Ritonavir or lopinavir/ritonavir greatly increase plasma concentrations of oxycodone in healthy human volunteers due to inhibition of CYP3A4 and CYP2D6. Rifampicin greatly reduces plasma concentrations of oxycodone due to strong induction of CYP3A4. There is also a case report of fosphenytoin, a CYP3A4 inducer, dramatically reducing the analgesic effects of oxycodone in a chronic pain patient. Dosage or medication adjustments may be necessary in each case.
Pharmacology
Pharmacodynamics
| Compound | Route | Dose |
| Codeine | 200 mg | |
| Hydrocodone | 20–30 mg | |
| Hydromorphone | 7.5 mg | |
| Hydromorphone | 1.5 mg | |
| Morphine | 30 mg | |
| Morphine | 10 mg | |
| Oxycodone | 20 mg | |
| Oxycodone | 10 mg | |
| Oxymorphone | 10 mg | |
| Oxymorphone | 1 mg |
Oxycodone, a semi-synthetic opioid, is a highly selective full agonist of the μ-opioid receptor. This is the main biological target of the endogenous opioid neuropeptide β-endorphin. Oxycodone has low affinity for the δ-opioid receptor and the κ-opioid receptor, where it is an agonist similarly. After oxycodone binds to the MOR, a G protein-complex is released, which inhibits the release of neurotransmitters by the cell by decreasing the amount of cAMP produced, closing calcium channels, and opening potassium channels. Opioids like oxycodone are thought to produce their analgesic effects via activation of the MOR in the midbrain periaqueductal gray and rostral ventromedial medulla. Conversely, they are thought to produce reward and addiction via activation of the MOR in the mesolimbic reward pathway, including in the ventral tegmental area, nucleus accumbens, and ventral pallidum. Tolerance to the analgesic and rewarding effects of opioids is complex and occurs due to receptor-level tolerance, cellular-level tolerance, and system-level tolerance.
Taken orally, 20 mg of immediate-release oxycodone is considered to be equivalent in analgesic effect to 30 mg of morphine, while extended release oxycodone is considered to be twice as potent as oral morphine.
Similarly to most other opioids, oxycodone increases prolactin secretion, but its influence on testosterone levels is unknown. Unlike morphine, oxycodone lacks immunosuppressive activity ; the clinical relevance of this has not been clarified.