How does Cigarette Smoke Affect the Effectivness of your Medication

Smoking cigarettes is a highly addictive habit that is ingrained in many people’s daily routines. As a result, the potential drug interactions of common medications with the compounds in tobacco are often overlooked (Chui et al. 2019). Cigarette smoke contains a class of compounds called Polycyclic aromatic hydrocarbons (PAHs), which are major lung carcinogens (Kroon 2007). PAHs can actually increase the production of certain drug-metabolizing enzymes, causing the potential for drug plasma concentrations to decrease at a quicker rate. This is an important factor in deciding medication doses for individuals with regular smoking habits. 

PAHs can induce their own metabolism by activating the aryl hydrocarbon receptor (AhR) in human vertebrate cells. Once the AhR is activated, it moves into the nucleus and forms a complex with the AhR nuclear translocator (ARNT). The AhR/ARNT complex binds to specific DNA sequences called dioxin response elements (DREs) or xenobiotic response elements (XREs) that are located in the promoter regions of target genes. This causes the increased expression of enzymes that are involved in PAH metabolism, including cytochrome P450 1A1 (CYP1A1) and 1A2 (CYP1A2) (Goedtke et al. 2020). As a result of this, the metabolism of other drugs that are substrates for CYP1A1 and CYP1A2 will also be increased. This includes drugs such as caffeine, clozapine, fluvoxamine, olanzapine, tacrine, and theophylline (Figure 1) (Kroon 2007). This might suggest that those who are regular smokers taking medications that interact with CYP1A1 and CYP1A2 would need to take higher dosages to reach the needed therapeutic effect. It also means that upon quitting smoking, smokers may require a reduction in the dosage of their medication, or else there could be adverse effects (Kroon 2007).

A study done by Faber and Fuhr looked into the time course of CYP1A2 activity changes after heavy smokers quit smoking. The participants smoked 20 cigarettes a day and CYP1A2 activity was recorded at days 6, 4, and 1 before sudden smoking cessation and days 1, 2, 3, 6, 8, 10, and 13 days after. The relative reduction in CYP1A2 activity after smoking cessation was 12.3% on day 1, 20.1% on day 2, 25.0% on day 3,  28.2% on day 4, and  36.1% at a steady state (which was approximately 1 week after smoking cessation). The apparent half-life that they calculated was 38.6 hours. This short half-life suggests that the dose of CYP1A2 substrate medications must be immediately changed after quitting smoking, especially in medications with short therapeutic ranges, to avoid adverse effects (Faber and Fuhr 2004).

The interaction between PAHs and CYP1A1 and CYP1A2 enzymes shows how cigarette smoke can potentially affect the drug plasma concentrations in regular smokers and reduce the therapeutic effect of the medication. However, these effects can rapidly change after smoking cessation, suggesting that medication dosages need to be immediately reassessed to avoid adverse effects. This highlights the importance of considering smoking habits when prescribing or taking certain medications. 

References

Chui, Chang Yue, Simone E. Taylor, Dennis Thomas, and Johnson George. 2019. “Prevalence and Recognition of Highly Significant Medication-Smoking Cessation Interactions in a Smoke-Free Hospital.” Drug and Alcohol Dependence 200 (July): 78–81. https://doi.org/10.1016/j.drugalcdep.2019.03.006.

Faber, Mirko S., and Uwe Fuhr. 2004. “Time Response of Cytochrome P450 1A2 Activity on Cessation of Heavy Smoking.” Clinical Pharmacology & Therapeutics 76 (2): 178–84. https://doi.org/10.1016/j.clpt.2004.04.003.

Goedtke, Lisa, Heike Sprenger, Ute Hofmann, et al. 2020. “Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells.” International Journal of Molecular Sciences 22 (1): 372. https://doi.org/10.3390/ijms22010372.

Grela, A., M. Kulza, W. Piekoszewski, M. Senczuk-Przybylowska, E. Gomolka, and E. Florek. 2013. “The Effects of Tobacco Smoke Exposure on Caffeine Metabolism.” Italian Journal of Food Science 25 (1): 76-. Gale Academic OneFile.

Kroon, Lisa A. 2007. “Drug Interactions with Smoking.” American Journal of Health-System Pharmacy 64 (18): 1917–21. https://doi.org/10.2146/ajhp060414.