Mechanism of action
The full mechanism of oxycodone is not known.Under conditions of inflammation or hyperalgesia, opioid receptors in the heart, lungs, liver, gastrointestinal tract, and reproductive system are upregulated and transported to nerve terminals.3 Oxycodone and its active metabolites, noroxycodone, oxymorphone, and noroxymorphone are opioid agonists.1 These compounds passively diffuse across the blood brain barrier or may be actively transported across by an unknown mechanism.3 Oxycodone and its active metabolites can selectively bind to the mu opioid receptor, but also the kappa and delta opioid receptors in the central nervous system and periphery, and induce a G protein coupled receptor signalling pathway.3 Activation of mu opioid receptors inhibits N-type voltage operated calcium channels, inhibiting responses to pain.
Oxycodone’s metabolism is hepatic and completed by 4 main reactions. CYP3A4 and 3A5 perform N-demethylation, CYP2D6 performs O-demethylation, unknown enzymes perform 6-keto-reduction, and unknown enzymes perform conjugation.1
Oxycodone is metabolized by CYP3A4 and CYP3A5 to noroxycodone and then by CYP2D6 to noroxymorphone.1 Noroxycodone and noroxymorphone are the primary circulating metabolites.Noroxycodone can also be 6-keto-reduced to alpha or beta noroxycodol.1
Oxycodone can be metabolized by CYP2D6 to oxymorphone and then by CYP3A4 to noroxymorphone.1 Oxymorphone can also be 6-keto-reduced to alpha or beta oxymorphol.
Oxycodone can also be 6-keto-reduced to alpha and beta oxycodol.1
The active metabolites noroxycodone, oxymorphone, and noroxymorphone can all be conjugated before elimination.1
Patients experiencing an overdose may present with respiratory depression, sleepiness, stupor, coma, skeletal muscle flaccidity, cold sweat, constricted pupils, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death.Overdose should be treated by maintaining airway, ventilation, and oxygenation.Label Oxygen and vasopressor treatment may be necessary to treat circulatory shock and pulmonary edema and defibrillation may be required for cardiac arrest of arrhythmia.Label Naloxone, nalmefene, or naltrexone may be used to counteract the effects of opioids but patients should be monitored in case further doses are required.Label
The intraperitoneal LD50 in mice is 320mg/kg, the oral LD50 is 426mg/kg.MSDS The oral lowest dose causing toxic effects in humans is 0.14mg/kg and subcutaneously in rats it is 1.53mg/kg.MSDS
Oxycodone is pregnancy category B according to the FDA.Label There is a paucity of data regarding oxycodone use in pregnancy, though animal studies show no teratogenic effects.Label Rats given oxycodone during lactation showed smaller offspring, though after lactation, they recovered to normal size.Label Oxycodone is excreted in breast milk and so patients should not breastfeed while taking oxycodone due to risk of sedation and respiratory depression in infants.Label
No studies on the carcinogenicity of oxycodone have been performed.Label Oxycodone was genotoxic at 50mcg/mL with metabolic activation and at 400mcg/mL without.Label It was also clastogenic with metabolic activation at ≥1250mcg/mL.Label Oxycodone was not found to be genotoxic in other tests.Label Oxycodone does not affect reproduction and fertility in rats at doses of up to 8mg/kg/day.Label