Detail:
Oxycodone is a semisynthetic opioid synthesized from thebaine, an opioid alkaloid found in the Persian poppy, and one of the many alkaloids found in the opium poppy. It is a moderately potent opioid pain medication (orally roughly 1.5 times more potent than morphine), generally indicated for relief of moderate to severe pain.Oxycodone was developed in 1917 in Germany as one of several semi-synthetic opioids in an attempt to improve on the existing opioids.
Oxycodone is available as single-ingredient medication in immediate release and controlled release. In the United Kingdom, it is available in 10 mg/mL and 50 mg/mL formulation for intramuscular or intravenous administration. Combination products are also available as immediate-release formulations, with non-narcotic analgesic ingredients such as paracetamol (acetaminophen) and nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen.
As it has euphoric effects similar to other opioids, oxycodone is one of the drugs abused in the current opioid epidemic in the United States. An abuse-deterrent combination with naloxone is available in managed-release tablets. If injected, the naloxone precipitates opioid withdrawal symptoms and blocks the effect of the medication. However, there have been concerns raised about the effectiveness of the abuse prevention measures.
Medical uses:
Oxycodone has been in clinical use since 1916, and it is used for managing moderate to moderately severe acute or chronic pain. It has been found to improve quality of life for those with many types of pain. Experts are divided regarding use for non-cancer-related chronic pain, as most opioids have great potential for dependence and have also been alleged to create paradoxical pain sensitivity.
Oxycodone is available as controlled-release tablet, intended to be taken every 12 hours. A 2006 review found that controlled-release oxycodone is comparable to instant-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 oral oxycodone as a second-line alternative to oral morphine for cancer pain.
In the U.S., extended-release oxycodone is approved for use in children as young as 11 years old. The approved indication is for relief of cancer pain, trauma pain, or pain due to major surgery, in children already treated with opioids, who can tolerate at least 20 mg per day of oxycodone; this provides an alternative to Duragesic (fentanyl) the only other extended-release opioid analgesic approved for children.
Side effects:
Two tablets (10 mg) of oxycodone and safety blisters.
Serious side effects of oxycodone include reduced sensitivity to pain (beyond the pain the drug is taken to reduce), euphoria, anxiolysis, feelings of relaxation, and respiratory depression. Common side effects of oxycodone include constipation (23%), nausea (23%), vomiting (12%), somnolence (23%), dizziness (13%), itching (13%), dry mouth (6%), and sweating (5%).[ Less common side effects (experienced by less than 5% of patients) include loss of appetite, nervousness, abdominal pain, diarrhea, urine retention, dyspnea, and hiccups.
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.
Oxycodone overdose has also been described to cause spinal cord infarction in high doses and ischemic damage to the brain, due to prolonged hypoxia from suppressed breathing.
Oxycodone in combination with naloxone in managed-release tablets, has been formulated to both deter abuse and reduce "opioid-induced constipation".
Dependence, addiction, 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 imbalance:
As with other opioids, chronic use of oxycodone (particularly with higher doses) often causes concurrent hypogonadism or hormone imbalance.
Absorption:
After a dose of conventional (instant-release) oral oxycodone, the onset of action is 10–30 minutes, and peak plasma levels of the drug are attained within roughly 30–60 minutes; in contrast, after a dose of OxyContin (an oral controlled-release formulation), peak plasma levels of oxycodone occur in about three hours. The duration of instant-release oxycodone is 3 to 6 hours, although this can be variable depending on the individual.
Distribution:
Oxycodone in the blood is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain. Conventional oral preparations start to reduce pain within 10–15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one hour.
Variation:
Oxycodone is metabolized by the cytochrome P450 enzyme system in the liver, making it vulnerable to drug interactions. Some people are fast metabolizers, resulting in reduced analgesic effect, but increased adverse effects, while others are slow metabolisers, resulting in increased toxicity without improved analgesia. The dose of oxycodone must be reduced in patients with reduced hepatic function.
Elimination:
Oxycodone and its metabolites are mainly excreted in the urine and sweat; therefore, it accumulates in patients with kidney impairment.
Bioavailability:
Oxycodone can be administered orally, intranasally, via intravenous, intramuscular, or subcutaneous injection, or rectally. The bioavailability of oral administration of oxycodone averages 60–87%, with rectal administration yielding the same results; intranasal varies between individuals with a mean of 46%.
Morphine equivalency:
Taken orally, 20 mg of immediate release oxycodone is equivalent to 30 mg of morphine. Extended release oxycodone is considered to be twice as potent as oral morphine.
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