Williams, David Glyn;
(2002)
Developmental and genetic factors affecting the efficacy of codeine.
Doctoral thesis (Ph.D.), University College London (United Kingdom).
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Abstract
Codeine is widely used for analgesia in paediatric medicine due to the perceived benefits of good pain relief combined with a low incidence of opioid related side- effects. Experimental evidence indicates that the analgesia obtained from codeine is either entirely or almost entirely dependent on its metabolism to morphine. This reaction is catalysed by the cytochrome P450 enzyme CYP2D6, which shows genetic polymorphism and decreased activity during early development. The aim of this thesis was to investigate how development and genetic variation may affect the ability of CYP2D6 to convert codeine to morphine and hence the efficacy of codeine. A rat model was used to look at the effect of development on efficacy. Rats at different stages of development were treated with either codeine or morphine and were subjected to one of a range of noxious stimuli. Neonatal rats, in whom the enzyme activity is low, showed a markedly reduced response to codeine compared to older animals treated with codeine and animals of all ages treated with morphine. However, analysis of plasma for morphine levels from these neonatal animals following codeine was inconclusive and no relationship between plasma morphine levels and effect could be found at any age. The effect of genetic variation on efficacy was investigated in a clinical study using children undergoing adenotonsillectomy. Children received either codeine or morphine and the analgesic effect was compared between the two groups, using two pain assessment tools, and also with plasma morphine levels and the genotype of the patient. Overall morphine and codeine appeared to provide equivalent analgesia but codeine showed more variability in its effect and there was a subgroup of patients in whom it appeared to provide little analgesia. However, it was not possible to link reduced efficacy to low plasma morphine levels or genetic variation.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Developmental and genetic factors affecting the efficacy of codeine |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | (UMI)AAIU642592; Health and environmental sciences; Codeine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10102453 |
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