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Dietary Supplements: A Framework for Evaluating Safety
but with no change in the plasma concentration of either. Pharmacodynamic interactions can result when two xenobiotics with similar pharmacological action produce an additive or synergistic response or when two xenobiotics with opposing pharmacological effects produce a reduced response. Predicting when a pharmacodynamic interaction may occur and the clinical results of this interaction depends on understanding the sites and mechanism of biological activity of both chemicals and predicting whether adequate levels are achieved at the sites of action.
Direct Pharmacodynamic Interactions
Direct pharmacodynamic interactions occur at the same site, such as an extracellular receptor or an enzyme where each xenobiotic exerts its pharmacological effect. The two xenobiotics may produce an additive physiological effect or, in the case of one being an antagonist or a weaker agonist, the result may be to decrease the response to the stronger agonist.
Indirect Pharmacodynamic Interactions
Indirect pharmacodynamic interactions occur when two xenobiotics act on the same physiological pathway from the receptor to the effector, but at different molecular sites of action. For example, two substances may each affect the same organ, but in different ways, and when taken together may greatly increase the propensity for organ damage, even if toxic effects are not detected independently.
Interactions with Dietary Supplements
There are examples of pharmacodynamic interactions that have been noted with dietary supplement ingredients. The antihypertensive effect of guanabenz acetate (a drug used for hypertension) is due to its central agonistic α-2-adrenoceptor activity (Grossman et al., 1993; Wenzel et al., 2001). Thus concomitant consumption of yohimbine bark, which contains an α-2-adrenoreceptor antagonist, may diminish the antihypertensive activity of guanabenz through its opposing pharmacodynamic effect. Another example is between the inotropic drug digitalis (Katzung, 2001) and hawthorne leaf or flower; data suggest that both the hawthorne leaf and the flower may also have a positive inotropic and electrophysiological effect on the heart (Schwinger et al., 2000). If digitalis and the hawthorne leaf or flower are taken together, the additive response may be excessive and lead to a serious adverse event (Schwinger et al., 2000). Another additive effect would be exhibited by the ginkgo leaf if its purported antagonism of platelet-activating factor occurred; if ingested with a cyclooxygenase inhibitor,