Oxycodone

Oxycodone is a drug in the opioid group used to treat moderate to severe pain. It is usually taken by mouth and is available in immediate-release and controlled-release (delayed-release) formulations. Pain relief usually begins within fifteen minutes and lasts up to six hours in the immediate-release formulation. Combination products with acetaminophen, ibuprofen, naloxone and aspirin are also available.

Pharmacodynamics

Oxycodone, a semisynthetic opioid, is a highly selective full agonist of the μ-opioid receptor. Oxycodone has a low affinity for the δ-opioid receptor and the κ-opioid receptor , where it is also an agonist. Binding to the opioid receptors results in an opening of potassium channels and a block of calcium channels, resulting in hyperpolarization of neurons in the brain. This makes nerve cells less excitable, suppressing pain transmission to the brain.

Pharmacokinetics

Oxycodone has an oral bioavailability of 60% to 87%, which is unaffected by food intake. Protein binding is 45%. In this regard, oxycodone is primarily bound to serum albumin. Hepatic metabolism of oxycodone is extensive and is accomplished by 4 major reactions. CYP3A4 and CYP3A5 perform N-demethylation, CYP2D6 performs O-demethylation, and 6-keto reduction and conjugation are performed by as yet unknown enzymes. Oxycodone and its metabolites are excreted in the urine. The established elimination half-life of oxycodone is 3.2 hours for immediate-release formulations and 4.5 hours for extended-release formulations.

Drug Interactions

Drug-drug interactions may occur when concomitantly taking substances that are also degraded or induced by the CYP3A4, CYP3A5, and CYP2D6 enzymes. Increased or decreased plasma levels of the drugs taken and significant side effects may occur.

Side effects

Common side effects are euphoria, constipation, nausea, vomiting, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating.

Severe side effects may include addiction, dependence, hallucinations, respiratory depression (a decrease in breathing), bradycardia, and low blood pressure. Those who are allergic to codeine may also be allergic to oxycodone.

The use of oxycodone in early pregnancy appears to be relatively safe.

The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent and oxycodone is abruptly discontinued. If oxycodone has been taken regularly for a long period of time, it should be discontinued gradually rather than abruptly. People who take oxycodone regularly as a recreational drug or at higher than prescribed doses are at even higher risk for severe withdrawal symptoms. Symptoms of oxycodone withdrawal, as with other opioids, may include anxiety, panic attacks, nausea, insomnia, muscle pain, muscle weakness, fever, and other flu-like symptoms.

Toxicological Data

LD50 (rat, oral): 320 mg-kg-1