This column is the fifth in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. Material in this series is adapted with permission from a recent book published by the first author, titled Drug-Drug Interactions With an Emphasis on Psychiatric Medications.1 The first 3 columns in this DDI series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs, how to recognize such DDIs, strategies for avoiding and/or minimizing adverse outcomes from such DDIs, and pharmacokinetic considerations concerning DDIs in psychiatric practice.2–4 The fourth column in this series presented a classificatory system based on mechanism of action and provided a table classifying neuropsychiatric medications by their major mechanisms of action rather than by their labeled therapeutic indications.5 This column presents a parallel table (Table 1) that summarizes major types of pharmacodynamic DDIs that can occur based on mechanism of action. This fifth column and the previous fourth column in this series are also adapted from and update an earlier 2-part series of columns published in this journal by the first author in 20036 and 20047 describing how neuropsychiatric drugs can be classified mechanistically and how DDIs can be predicted based on the mechanisms of action of one or more drugs used together.
The need to understand both the potential effect(s) of a drug alone and its potential to interact pharmacodynamically with other co-prescribed drugs is the rationale for classifying drugs in terms of their pharmacodynamic mechanisms of action. The reader can thus use Table 1 in part 4 of this series5 and Table 1 in this column to predict pharmacodynamically mediated DDIs—both for the purposes of producing therapeutic DDIs and avoiding adverse DDIs.
Table 1 in this column follows the same format as its companion table in the preceding column.5 It is organized alphabetically by neurotransmitter or neural mechanism of action. For example, it begins with a section on acetylcholine that covers muscarinic acetylcholine receptor antagonism and cholinesterase inhibition. The table points out that muscarinic acetylcholine receptor antagonists can be used to mitigate the extrapyramidal symptoms produced by excessive use of dopamine-2 receptor antagonists (eg, haloperidol), as an example of a therapeutic pharmacodynamic DDI, and for the same reason can block the memory-enhancing effects produced by cholinesterase inhibitors such as donepezil, as an example of an adverse pharmacodynamic DDI.
A caveat to remember when using these 2 tables is that some drugs can affect >1 mechanism of action at their usual therapeutic concentrations, a caveat that is germane to a number of antidepressants and antipsychotics (for further discussion of this topic, see earlier columns on the pharmacology of antidepressants and antipsychotics, including so-called low-potency antipsychotics from the 1950s and so-called atypical antipsychotics from the 1990s8–13). To address this issue, the reader is referred to a recently published book by one of the authors (S.H.P.), which contains tables showing the relative binding affinity of a number of antidepressants and antipsychotics for various neural mechanisms of actions.1 These tables will be presented in subsequent columns in this series. The prescriber needs to keep this issue and such data in mind because some drugs—a classic example is amitriptyline—can interact in multiple ways with many other drugs due to their multiple mechanisms of action.14
This column and the preceding fourth column5 in this series on DDIs update an earlier 2-part series of columns on a mechanism-based classificatory system of psychiatric medications published in 20036 and 20047 by adding drugs to the tables that have been approved since the earlier series was published. This mechanism-based system allows the prescriber to predict the action of a neuropsychiatric drug when used alone as well as to predict pharmacodynamically mediated DDIs that may occur when the drug is used in combination with other mechanistically classified drugs.
These 2 columns and their tables complement earlier columns in this series, which described how drugs can be classified in terms of their pharmacokinetics and effects on pharmacokinetic mechanisms. For example, drugs can be classified according to what enzymes, if any, are responsible for their biotransformation as a necessary step in their eventual elimination from the body and whether the drugs are inhibitors or inducers of those enzymes. That enzymatic classification scheme can then be used to predict pharmacokinetic DDIs mediated by cytochrome P450 enzymes (Fig. 1), just as the mechanism-based classification system presented here can be used to predict pharmacodynamic-based DDIs.
Many patients are taking psychiatric medications and the number has been continuously increasing over the past 3 decades, with antidepressants even surpassing antihypertensives to become the most commonly prescribed class of medications in 2005.15 Patients on psychiatric medications are more likely to be receiving complex medication regimens than those not taking psychiatric medications, increasing their risk for experiencing a DDI. It is important that prescribers of psychiatric medications understand fundamental principles of pharmacology and good clinical management to avoid unintended and untoward DDIs. The ultimate intent of these series and a recurring theme of this column overall is to present a simple way of conceptualizing neuropsychiatric medications in terms of their pharmacodynamics and pharmacokinetics to allow prescribers to take these facts into consideration when they need to use more than one drug in combination to optimally treat a patient.
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