TOXICOLOGY
Induce With Caution: The Clinical Relevance of Enzyme Induction in Poisoned Patients By Andrew Posen, PharmD, and Jennifer Lee, PharmD, on behalf of the SAEM Academy of Emergency Medicine Pharmacists Toxicology Writing Group
SAEM PULSE | NOVEMBER-DECEMBER 2025
The Role of Enzyme Activity in Detoxification
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The body’s ability to detoxify and eliminate drugs relies heavily on enzyme activity. In most cases, drugs undergo biotransformation into more hydrophilic compounds by the hepatic cytochrome P450 (CYP) enzyme family and conjugating enzymes such as glucuronosyltransferases. The level of enzyme activity varies according to genetics and clinical conditions, and can be modified by diet, environmental pollutants, and drug therapy. Both enhanced and depressed enzyme functionality can have toxic ramifications, with drug–
drug interactions being a notable example. Conversely, harnessing this knowledge may inform therapeutic options for poisoned patients.
Understanding Enzymatic Induction
Enzymatic induction refers to amplified enzyme activity occurring as an adaptive response to xenobiotic exposure—the inducer. The specific inductive mechanism is most influential to the clinical effect. Classically, ligand binding and nuclear receptor–mediated transcriptional activation upregulate expression of the target enzyme, with an average onset of one to two weeks.
Some processes occur more rapidly, and the magnitude of induction ultimately depends on the inducer’s potency, dose, halflife, and the affected drug’s halflife. In the context of drug–drug interactions, inducers may enhance the conversion of prodrugs to active metabolites or diminish the effect of active parent drugs. Common pharmacologic inducers include rifampin, phenytoin, and St. John’s wort. A thorough medication history is essential for identifying these agents and their associated risks. For instance, a patient who initiates the herbal supplement St. John’s wort may experience decreased effectiveness of an