ANTIDOTE TOXICITY: WHEN THE CURE BECOMES THE POISON
DOI:
https://doi.org/10.32782/2411-9164.23.2-6Keywords:
antidotes, clinical toxicology, drug toxicity, iatrogenesis, pharmacological safetyAbstract
In clinical toxicology, antidotes are traditionally viewed as «magic bullets» capable of specifically neutralizing a poison. However, this perception is dangerously simplistic, as antidotes themselves are potent pharmacological agents with significant inherent potential for iatrogenic toxicity. Objective. The purpose of this review article is to critically analyze the paradox of antidote therapy. The objective is to move beyond the traditional «antidote-poison» pairing and to classify common antidotes based on the fundamental mechanisms by which they cause toxicity, drawing upon contemporary scientific literature. Methods. A critical analysis and synthesis of modern scientific literature (including systematic reviews, clinical trials, and case reports) was conducted to identify, categorize, and describe the mechanisms of iatrogenic toxicity associated with the use of common antidotes in emergency medicine. Results. The analysis demonstrates that antidote toxicity is a predictable pharmacological event. A classification framework is proposed, grouping toxicity mechanisms into four categories: (1) Toxicity via excessive pharmacological antagonism (e.g., naloxone-precipitated acute withdrawal; flumazenil-induced seizures by unmasking pro-convulsant effects in mixed overdoses); (2) Inherent or direct toxicity (e.g., N-acetylcysteineinduced anaphylactoid reactions; methylene blue’s dose-dependent oxidant effects and MAO inhibition; nitrite-induced iatrogenic methemoglobinemia); (3) Toxicity of chelation therapy (e.g., deferoxamine-induced hypotension and infection potentiation; dimercaprol-mediated metal redistribution to the CNS; EDTA-induced hypocalcemia and nephrotoxicity); and (4) Toxicity from metabolic manipulation (e.g., sodium bicarbonate-induced hypokalemia and alkalosis; complications of high-dose insulin euglycemic therapy). Conclusions. Antidote-induced harm is not an anomaly but an expected consequence of its pharmacology. This necessitates a paradigm shift from reflexive, protocol-based administration to a considered, individualized risk-benefit assessment. Practical recommendations for clinicians are formulated (e.g., avoiding «coma cocktails», titrating to clinical effect), and the importance of future pharmacogenetic research (e.g., G6PD deficiency) for personalizing therapy is emphasized.
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