Questions: The 25 year old male who had a CYP2D6 */4/*/40 genotype (CYP2D6 poor metabolizer) that we met previously, is now presenting with depression. What is potential implication of prescribing nortriptyline according to CPIC (Clinical Pharmacogenetics Implementation Consortium) guideline recommendation for this genotype listed in pharmgkb.org? The patient experiences poor efficacy. The patient has an increased probability of adverse reactions. The patient should receive higher than typical dosing. We cannot predict how the patient will react to

The answer is the second one: The patient has an increased probability of adverse reactions.

Explanation for each option:

1. The patient experiences poor efficacy.
   This option is incorrect. While poor metabolizers may experience altered drug efficacy, the primary concern with nortriptyline in CYP2D6 poor metabolizers is the increased risk of adverse reactions due to higher plasma concentrations of the drug.

2. The patient has an increased probability of adverse reactions.
   This option is correct. According to the CPIC guidelines, individuals with a CYP2D6 poor metabolizer status, like the patient with the _4/_40 genotype, are at risk of higher plasma levels of nortriptyline. This can lead to an increased probability of adverse reactions, as the drug is not metabolized efficiently.

3. The patient should receive higher than typical dosing.
   This option is incorrect. For CYP2D6 poor metabolizers, the recommendation is often to reduce the dose rather than increase it, to avoid potential toxicity due to slower drug metabolism.

4. We cannot predict how the patient will react to.
   This option is incorrect. The CPIC guidelines provide specific recommendations for CYP2D6 poor metabolizers, indicating that we can predict an increased risk of adverse reactions due to higher drug levels.

In summary, the patient with a CYP2D6 poor metabolizer genotype is likely to have increased plasma levels of nortriptyline, leading to a higher risk of adverse reactions.