Those researchers, Cozza, Armstrong and Oesterheld, who constantly report on drug-drug interactions [DDI], have confirmed what I have seen in the office since 1996 – regarding CYP 450 2D6 interactions and my experience of regularly witnessing reactions to Prozac and Paxil with Adderall in hundreds of cases over many years.
Drug Interaction Principles For Medical Practice – Wynn, Oesterheld, Cozza, and Armstrong – 2008
Polymorphisms of CYP450 2D6 make that interaction more unpredictable – and deniable.
In comments on another CorePsych post regarding ADD and Vyvanse titration Eddie brought to my attention another drug-drug interaction you should know about:
Antihistamines block 2D6 as well. For complete transparency, you must know that I keep the Cozza, Armstrong and Oesterheld book right by my side all day every working day, but this is still a new one for me. I haven’t been watching for this interaction, but it looks like something we should all keep on our radar. Review this article on Antihistamines and 2D6, relevant for AMP, less so for methylphenidate. This table breaks down different generations of antihistamines – and in the body of the article indicates more about 2D6 interactions than is on this table.
This warning is not dire, – it’s not necessary to exclude the more efficacious AMP from your treatment program, just watch for a possible reaction. Most often these reactions aren’t dangerous, but create treatment adverse consequences that cause the team to stop the better [AMP] intervention.
“The “classic” or sedating antihistamines, with diphenhydramine (Benadryl® and others) as the prototype, are greatly effective but rife with side effects, most notably sedation. In fact, they are often found in over-the-counter sleeping aids, allergy remedies, and numerous multicompound preparations for “colds and flu.” Finkle et al.3 indicated that 47% of people with allergies take over-the-counter medications that typically contain a first-generation antihistamine.”
This will be interesting to watch, and may be contributory to some of the “unpredictable” reactions with stimulants.
And, by the way, when you read it you will be reading also about the “narrowing of the Therapeutic Window” in their report – for many more articles on ‘The Therapeutic Window with ADD Treatment‘ drill down to the bottom of this EzineArticles page.
From: Nursing Link–
The CYP450 enzyme system is a key pathway for drug metabolism. Many lipophilic drugs must undergo biotransformation to more hydrophilic compounds to be excreted from the body. Drug biotransformation reactions consist of Phase I (e.g., oxidation, reduction) or Phase 2 (e.g., conjugation) reactions that occur primarily in the liver. The most common Phase I reaction is oxidation, which involves the insertion of an oxygen atom into the compound to form a polar hydroxyl group. Of the enzymes involved in Phase I reactions, the CYP450 group is the most important.
Cytochromes P-450 are a superfamily of hemoproteins which can be divided into families, subfamilies and/or single enzymes.3 The cytochrome P-450 enzymes act as a major catalyst for drug oxidation. To unify nomenclature, a given gene family is defined as having >40% amino acid sequence homology and a subfamily as having >55% identical sequence homology Using this nomenclature, the cytochrome P450 enzymes are designated by the letters CYP (representing cytochrome P450), followed by an Arabic numeral denoting the family, a letter representing the subfamily (when 2 or more exist) and another Arabic numeral designating the individual gene within the subfamily (e.g., CYP2D6).
Each enzyme is termed an isoform (or isoenzyme) since it is derived from a different gene.5 An important subset of the cytochrome P450 family is the CYP3A4 isoenzyme, which accounts for nearly 60% of the total CYP450 in the liver and approximately 70% in the intestine.6 CYP3A4, which catalyzes the biotransformation of many drugs, is significantly expressed extrahepatically. Extensive metabolism by CYP34A in the gastrointestinal tract contributes to the poor oral bioavailability of many drugs.
Many substrates, inhibitors and inducers of CYP3A4 have been identified. By definition, a substrate is a drug that is metabolized by an enzyme system. An inhibitor decreases the activity of the enzyme and may decrease the metabolism of substrates, generally leading to an increased drug effect. Inducers, however, may increase the metabolism of substrates and generally lead to a decreased drug effect.
Thanks Eddie, – thanks Wynn, Cozza, Armstrong, and Oesterheld.
Dr Charles Parker
Author: New ADHD Medication Rules – Brain Science & Common Sense
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