Question

Interaction with the enzyme cytochrome P450 (CYP) 2D6 has what bearing on the use of tricyclic antidepressants?

A. None; tricyclics do not interact with CYP 2D6
B. Those with decreased CYP 2D6 activity will have lower than expected plasma drug concentrations
C. Giving a patient on a tricyclic a CYP 2D6 inhibitor could cause a drop in the plasma concentration of the drug
D. Cimetidine can cause an increase in tricyclic levels as a result of its interaction with CYP 2D6
E. Concomitant use of drugs that inhibit CYP 2D6 with tricyclics may necessitate higher than usual prescribed doses of

Answer 1

Cytochrome P450 (CYP) 2D6 plays a crucial role in the metabolism of tricyclic antidepressants. Inhibitors of CYP2D6 can increase plasma levels of tricyclics, potentially requiring dose adjustments to maintain therapeutic efficacy and avoid toxicity.

Step-by-step explanation:

The interaction of tricyclic antidepressants with the enzyme cytochrome P450 (CYP) 2D6 is significant in the pharmacokinetics of these medications. Tricyclics, including drugs like imipramine and amitriptyline, are metabolized by CYP2D6. When a patient with decreased CYP2D6 activity is given tricyclic antidepressants, their plasma drug concentrations may be higher than expected, because the drug is not metabolized as efficiently. Additionally, if a CYP2D6 inhibitor is given, this could potentially lead to an increase in plasma concentrations of the tricyclic, as it would compete for metabolism by the enzyme, thus slowing down the clearance of the antidepressant from the body. A well-known CYP2D6 inhibitor such as cimetidine can indeed cause an increase in tricyclic levels. Consequently, when tricyclic antidepressants are co-administered with drugs that inhibit CYP2D6, the prescriber may need to adjust the doses of the tricyclics appropriately to avoid toxicity or therapeutic ineffectiveness.