Pharmacodynamic vs Pharmacokinetic
The different types of interactions that are spoken about with kava.
Hello kava lovers, today’s topic will be regarding the different types of interactions we speak of. There are two distinct types of interactions that we should note. These two are pharmacodynamic and pharmacokinetic. Pharmacokinetics and pharmacodynamics are often spoken of in terms of kava consumption. It is a good idea to understand the basics of both.
Pharmacokinetics: This is defined as the study of the absorption, distribution, metabolism, and excretion of drugs and compounds in the human body and other compartmental systems (Spruill 2013). We will address this word in the context of kava interactions in the realm of CYP enzyme metabolism.
Pharmacodynamics: This term refers to the relationship between drug concentration at the site of action and the resulting effect of the compound at this site. This includes intensity of effects and adverse effects (Spruill 2013). We’ll be arriving at this location based on the effects of pharmaceutical drugs and alcohol that cause differences in perceived effects related to kava consumption.
An example of a pharmacokinetic interaction would be how kava may extend the half-life and consequently raise the serum concentration of drugs that specifically use the CYP2E1 metabolic pathway for metabolization. Kava has an inhibitory effect on this pharmacogene based on a study in 2005 in which it was found that kava inhibitedCYP2E1 in vivo to a ~40% reduction in healthy volunteers (Gurley et al. 2005). CYP2E1 participates in the metabolism of anesthetics, ethanol (in chronic consumption), nicotine, APAP (acetaminophen/Tylenol), and chlorzoxazone, among others. CYP2E1 also plays a role in the activation of toxic precarcinogens in tobacco smoke and nitrosamine compounds (García-Suástegui et al. 2017). On a personal note, this reduction in 2E1 could explain why people suddenly begin smoking less cigarettes after starting to drink kava regularly. This reduction in metabolism enzyme due to kava may extend the half-life and therefore effects profile of nicotine. Effects on CYP2E1 may also explain a portion of kava’s anti-cancerous profile, as 2E1 plays a part in activating precancerous compounds. Kava’s inhibitory effect may be reducing the amounts of these chemicals that make it to systemic circulation, thereby reducing the cancerous effects of tobacco consumption.
One example of a pharmacodynamic interaction is alcohol. The combination of alcohol and kava further decreased cognition, coordination, and attention and increased general levels of intoxication. (Foo and Lemon 1997). Another example would be ADHD medications. Kava was shown to reduce amphetamine-related hyperactivity and conditioned place avoidance in rodents, indicating that it likely will counteract some of the stimulating properties seen in these types of medications (Volgin et al. 2020). Pharmacodynamic effects will also extend to those of antidepressants based on their method of action, and certainly to anxiolytics such as benzodiazepines. These interactions may increase or blunt the physiological and/or psychological effects of kava.
In summary, pharmacodynamic interactions are those that occur between the main effects of two or more substances. Pharmacokinetic interactions occur when changes are incurred in the process of metabolization and excretion by one or more compounds, affecting the elimination or activation of others.
Foo, H., and J. Lemon. 1997. “Acute Effects of Kava, Alone or in Combination with Alcohol, on Subjective Measures of Impairment and Intoxication and on Cognitive Performance.” Drug and Alcohol Review 16 (2): 147–55. https://doi.org/10.1080/09595239700186441.
García-Suástegui, W. A., L. A. Ramos-Chávez, M. Rubio-Osornio, M. Calvillo-Velasco, J. A. Atzin-Méndez, J. Guevara, and D. Silva-Adaya. 2017. “The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain.” Oxidative Medicine and Cellular Longevity 2017 (January): 4680732. https://doi.org/10.1155/2017/4680732.
Gurley, Bill J., Stephanie F. Gardner, Martha A. Hubbard, D. Keith Williams, W. Brooks Gentry, Ikhlas A. Khan, and Amit Shah. 2005. “In Vivo Effects of Goldenseal, Kava Kava, Black Cohosh, and Valerian on Human Cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 Phenotypes.” Clinical Pharmacology and Therapeutics 77 (5): 415–26. https://doi.org/10.1016/j.clpt.2005.01.009.
Spruill, William J. 2013. “Introduction to Pharmacokinetics and Pharmacodynamics.” In Concepts in Clinical Pharmacokinetics, 18.
Volgin, Andrey, Longen Yang, Tamara Amstislavskaya, Konstantin Demin, Dongmei Wang, Dongni Yan, Jingtao Wang, et al. 2020. “DARK Classics in Chemical Neuroscience: Kava.” ACS Chemical Neuroscience https://doi.org/10.1021/acschemneuro.9b00587.