Therefore, its clearance can be altered by inhibitors and inducers of these enzymes, increasing and decreasing half-life, respectively. (For lists of CYP3A4 and CYP2D6 inhibitors and inducers, see here and here, 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
Oxycodone, a semi-synthetic opioid, is a highly selective full agonist of the μ-opioid receptor (MOR). This is the main biological target of the endogenous opioid neuropeptide β-endorphin. Oxycodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), 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 (PAG) and rostral ventromedial medulla (RVM).
Rieveschl worked with Parke-Davis to test the compound, and the company licensed the patent from him. In 1947 Parke-Davis hired him as their Director of Research. While he was there, he led the development of orphenadrine, an analog of diphenhydramine.Prior to the development of amantadine in the late 1960s and then other drugs, anticholinergics like orphenadrine were the mainstay of Parkinsons treatment. Formulation
Orphenadrine has been available as a citrate salt and a hydrochloride salt; in the US as of February 2016 the citrate form was available in tablets, extended release tablets, compounding powder and by injection for acute use in a hospital setting.Orphenadrine is often available mixed with aspirin, paracetamol/acetaminophen, ibuprofen, caffeine, and/or codeine.The brand names Norflex and Norgesic are formulations of the citrate salt of orphenadrine and Disipal is the hydrochloride salt. Chemistry
Orphenadrine is a derivative of diphenhydramine with a methyl group added to one of the phenyl rings. Stereochemistry
Orphenadrine has a chiral center and two enantiomers. When employed as a therapeutic agent, it is typically supplied as the racemate. References
External links
MedlinePlus DrugInfo medmaster-a682162