There's so much to discover with drug interactions
I became a pharmacist because of my love of science and people. Plus, I love the idea of continual learning. There is so much to discover about pharmacy as a career, how to interact with our patients and new, innovative medicines. Sometimes, though, we stumble on interesting information about new ways our bodies and medicine interact that we can’t help sharing with others.
As pharmacists we are aware of how important the cytochrome P450 system is to drug metabolism. But did you know that inflammation can cause down-regulation of these enzymes?1 Expression of our P-450 system is modulated by cytokines in inflammation, like increased tumor necrosis factor 𝛼(TNF𝛼), causing down-regulation.2 Once inflammation has been under control, the cytochrome P450 system is able to normalize.3 It is recommended to monitor drugs that have a narrow therapeutic index like warfarin or drug concentration like cyclosporine or theophylline.4 It’s important to monitor these drugs when starting and stopping medications that affect TNF𝛼like golimumab or adalimumab.
This blew my mind. Think about how often we have patients who struggle with chronic pain and inflammation. Often depression and chronic pain are intertwined. Many medications used to treat depression are metabolized by the P450 system.5 It’s important to keep this in mind so that those who may be struggling while finding the right treatment, have the tools to help them navigate this trying time in their clinical story. Research in animal models and primary hepatocytes has shown various effects of cytokines on P450 expression and activity but prediction of changes due to drug exposure in patients is trickier. A patient’s response to inflammation can vary greatly due to disease state, its time course and which P450 is involved. Further research on endogenous markers of P450 metabolism would provide insight when reevaluating drug dosage and choice of therapy.6
So, while we wait for the science to catch up, what can we do to help our patients now? I think when we have patients who are starting or stopping medications that modulate inflammation, we need to be mindful of the potential for drug interactions with drugs that are metabolized by the P450 system. Be mindful of how their therapy is affected by the P450 system. Is it cleared or activated? Are the side effects the patient experiencing possible toxicities of their other therapies? Or signs that their co-diagnosis is not managed well with their current therapy?
Rachel Luther is a graduate from Memorial University of Pharmacy. She owns Centre Wellington Remedy’s Rx in Fergus, Ont. where she lives with her husband and two kids. Rachel’s focus is on patient centred care and professional services. When not at work, she is out looking for mushrooms or sewing.
1Role of Cytochrome P450s in Inflammation. Peter Christmas. https://pubmed.ncbi.nlm.nih.gov/26233907/Adv Pharmacol. 2015;74:163-92. doi: 10.1016/bs.apha.2015.03.005. Epub 2015 Jun 30.
2Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Z Abdel-Razzak, P Loyer, A Fautrel, J C Gautier, L Corcos, B Turlin, P Beaune and A Guillouzo. Molecular Pharmacology October 1993, 44 (4) 707-715;
3Front. Pharmacol., 16 November 2021 | https://doi.org/10.3389/fphar.2021.733935 Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Camille Lenoir1,2*, VictoriaRollason1,3, Jules A. Desmeules1,2,3 and Caroline F. Samer1,3
4CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2022 [updated 2019 JUN 20; cited 2022 JUN 14].Simponi[productmonograph].Available from: http://www.e-therapeutics.ca
5The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects. TOM LYNCH, PharmD, AND AMY PRICE, MD. Am Fam Physician. 2007;76(3):391-396
6Role of Cytochrome P450s in Inflammation. Peter Christmas. https://pubmed.ncbi.nlm.nih.gov/26233907/Adv Pharmacol. 2015;74:163-92. doi: 10.1016/bs.apha.2015.03.005. Epub 2015 Jun 30.