Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine

Abstract

The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O-demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p less than 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment.

The analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by experimentally induced pain

“…Arendt-Nielsen, Øberg and Bjerring [18] used brief argon laser pulses covering a small area to determine the analgesic effect of alfentanil. The same method has also been used to show an analgesic effect of weak analgesics [19][20][21]. Ice water stimulation has been used to demonstrate an analgesic effect of morphine [7,22], but it failed to detect an analgesic effect of acetylsalicylic acid [22] and ibuprofen [7].…”

Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications

“…This is a concern for cancer patients being given pain relief, with a lower analgesic effect of codeine seen in PMs, as conversion of the drug to morphine is CYP2D6-dependent [58,59]. This could also be an issue for the antiemetic dolasetron, as CYP2D6 is also required for its conversion to the active metabolite hydrodolasetron.…”

“Target-Site” Drug Metabolism and Transport

“…CYP2D6 genetic variation can alter codeine-induced analgesia: genetically poor metabolizers do not exhibit an analgesic response to codeine due to their inability to convert codeine to morphine (Sindrup et al, 1990(Sindrup et al, , 1992Chen et al, 1991). This metabolic activation is mediated mainly by CYP2D6 in the liver, and morphine subsequently crosses the blood-brain barrier and elicits analgesia.…”