A Study On A Patient Administered A Typical Dose Of Codeine Essay

1957 Words Apr 9th, 2015 null Page
6. A patient administered a typical dose of codeine experiences rapid onset of respiratory depression (slowed breathing) within one hour and requires breathing assistance. He has a brother who had a similar response to codeine.
If this is a pharmacogenetic-related effect, what is the most likely genetic cause underlying this adverse drug response?
If it is a pharmacogenetics –related effect then both the brothers are ultra-rapid metabolizers (UM) of codeine, meaning they have extra copies of the CYP2D6 allele. Codeine is a pro-drug and is metabolized to morphine which is an active metabolite by the CYP2D6 enzyme. Genetic variations on the CYP2D6 will lead to increased or reduced activity of the enzyme. An UM has very high activity and therefore, are at a higher risk of toxic side effects like sedation or respiratory depression. (2-13 copies of the CYP2D6 gene).
How will this patient likely respond to the tricyclic antidepressant nortriptyline (PamelorC)?
If the patient is given antidepressant nortriptyline:
Nortriptyline is metabolized by CYP2D6 to a less active hydroxyl metabolite, 10-hydroxy nortriptyline (50% of parent drug’s activity). This patient is a CYP2D6 UM and so has very high enzyme activity. He will show increased metabolism to the less active metabolite and there will be low plasma concentrations of parent drug, which will increase the probability of treatment failure. It would be better to start him on an alternate agent that is not metabolized by CYP2D6.…

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