Abstract
ABSTRACT
Contemporary pharmacotherapy has improved disease‐specific outcomes, but prescribing for multimorbidity remains largely guideline‐driven, endpoint‐focused, and insufficiently sensitive to cumulative treatment burden in patients with limited physiological reserve. Mitochondrial dysfunction and redox imbalance are shared biological processes that shape disease vulnerability, adaptive capacity, and susceptibility to drug‐related toxicity; however, they are rarely operationalized in medication review or deprescribing. This mechanism‐informed narrative review integrates mechanistic, translational, and clinical literature on redox–mitochondrial biology, drug‐class‐specific mitochondrial liabilities, polypharmacy, frailty, and deprescribing, with searches conducted through 2024 and targeted updates through June 2026. Primary clinical and preclinical examples are used to illustrate pharmacological plausibility for selected drug classes, and structured tables and a prioritization algorithm translate these concepts into pragmatic medication‐review signals. We propose redox–mitochondrial reasoning as a complementary lens for interpreting treatment intolerance, functional decline, and cumulative medication burden as possible evidence of mismatch between pharmacological exposure and a patient's adaptive capacity. The proposed framework is explicitly conceptual: its vulnerability strata, algorithm, and decision categories are heuristic aids rather than validated clinical prediction instruments. It should therefore be used only alongside established deprescribing tools, individualized benefit–harm assessment, and shared decision‐making.