The body responds to drugs based on several factors. Obviously, our genetic make-up affects our unique response to drugs, but lifestyle habits can also determine the effectiveness of drug-based treatment for each individual.
First, the way our bodies assimilate drugs is affected by diet in general, as well as certain supplements. The best-known example of this is grapefruit juice. Like clementines, grapefruit contains so-called furanocoumarins, compounds that interfere with the action of the CYP (or cytochrome P450) liver enzymes involved in drug metabolism.1 For instance, when a person drinks grapefruit juice, the action of CYP3A4 (an enzyme involved in the metabolism of many pharmaceutical agents) is inhibited. This leads to abnormally high accumulations of the drug in the person’s body2 and could have a similar effect to taking too high a dose. When there is too much of the anticoagulant warfarin in the blood, for example, this could lead to serious hemorrhage.3 Similarly, St. John’s wort, a herbal made from the Hypericum perforatum plant, is often consumed for its medicinal properties.4 However, it is a CYP3A4 inducer or, in other words, it makes this enzyme more active.5,6 This means that drugs are metabolized more rapidly, as evidenced by lower drug concentrations – as though patients had taken a smaller dose than was actually given. Taxol and tamoxifen are chemotherapy drugs used to treat certain cancers. Because they are both metabolized by CYP3A4, patients treated with these drugs would have lower concentrations of them in the body, which could reduce the effectiveness of any treatment aimed at inhibiting tumour growth.7,8
Smoking is an everyday habit for many people that can have unwanted side effects when combined with certain drugs. Chronic tobacco use increases the action of CYP1A2, another cytochrome that is involved in metabolizing anti-psychotic drugs such as clozapine and haloperidol.9,10 This leads to lower concentrations of antipsychotics in the body, and the prescribed doses may be insufficient to alleviate the symptoms of the mental disorders.
Regular consumption of either small or large quantities of alcohol should be avoided during drug-based treatment, as alcohol inhibits the effectiveness of some cytochromes and induces others. CYP2E1, for example, the enzyme that metabolizes acetaminophen, better known as Tylenol™, is more active and hence metabolizes drugs faster in the presence of alcohol.11,12 However, a by-product of acetaminophen metabolism is the extremely toxic substance known as NAPQ1, which must be rapidly eliminated from the body.13 When alcohol is present in the body, the levels of NAPQ1 produced are comparable to excessive intake of acetaminophen verging on an overdose, and lead to liver damage and even potentially fatal liver failure. This is why healthcare professionals often advise against consuming alcohol while taking medication.
In conclusion, to get the safest and most effective treatment, be sure to follow the recommendations on drug interactions made by your doctor or pharmacist.
A Master's student in biochemistry, Nadia is passionate about science and loves to stay on top of the most recent discoveries in such fields as genetics, molecular biology and medicine. Because of her experience working in a lab, she is particularly interested in the development of new drugs and how patients respond to them. She wants to share some of her knowledge by writing these articles and, most of all, wants to be constantly learning about the field of pharmacogenetics.
- Theile, D. et al. Clementine juice has the potential for drug interactions – In vitro comparison with grapefruit and mandarin juice. Eur. J. Pharm. Sci. 97, 247–256 (2017).
- Paine, M. F., Criss, A. B. & Watkins, P. B. Two Major Grapefruit Juice Components Differ in Time to Onset of Intestinal CYP3A4 Inhibition. J. Pharmacol. Exp. Ther. 312, 1151–1160 (2005).
- Leonard, J., Laurence, F. & Howes, G. Drug Interactions of Direct-Acting Oral Anticoagulants. Drug Saf. 39, 841–845 (2016).
- Jon, E. & Lee, D. Pharmacokinetic interactions of drugs with St John’s wort. J. Psychopharmacol. 18, 262–276 (2004).
- Sprouse, A. A. & Breemen, R. B. Van. Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements. Drug Metab. Dispos. 44, 162–171 (2016).
- Johne, A. et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort. Clin. Pharmacol. Ther. 66, 338–345 (1999).
- Stage, T. B., Bergmann, T. K. & Kroetz, D. L. Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review. Clin. Pharmacokinet. (Epub), (2017).
- Binkhorst, L., Mathijssen, R. H. J., Jager, A. & Gelder, T. Van. Individualization of tamoxifen therapy : Much more than just CYP2D6. Cancer Treat. Rev. 41, 289–299 (2015).
- Spina, E. & Leon, J. De. Clinical applications of CYP genotyping in psychiatry. J. Neural Transm. 122, 5–28 (2015).
- Babu, S., Koramannil R, Saradalekshmi Indu V, N., Chandrasekharan, N. & Banerjee, M. Pharmacoepigenomic responses of antipsychotic drugs on pharmacogenes are likely to be modulated by miRNAs. Epigenomics 9, 811–821 (2017).
- Na, S. et al. The induction of cytochrome P450 2E1 by ethanol leads to the loss of synaptic proteins via PPAR α down-regulation. Toxicology 385, 18–27 (2017).
- Yuan, J. et al. Ferulic acid attenuated acetaminophen-induced hepatotoxicity though down-regulating the cytochrome P 2E1 and inhibiting toll-like receptor 4 signaling-mediated inflammation in mice. Am. J. Transl. Res. 8, 4205–4214 (2016).
- Mund, M. E., Quarcoo, D., Gyo, C., Brüggmann, D. & Groneberg, D. a. Acetaminophen as a toxic substance for children: aspects of legislation in selected countries. J. Occup. Med. Toxicol. 10, 43 (2015).