CHSU Discovery

Topical anesthetics are widely employed in dermatology for cosmetic interventions, laser therapies, and minor surgical procedures. Although generally safe, their systemic absorption is highly influenced by the integrity of the epidermal barrier. Inflammatory skin disorders such as psoriasis and atopic dermatitis compromise the stratum corneum (SC), facilitating enhanced percutaneous absorption and elevating the risk of systemic toxicity. This concern is particularly pertinent for potent agents such as lidocaine, tetracaine, and prilocaine, which, at elevated plasma concentrations, can induce central nervous system and cardiovascular complications, including seizures and arrhythmias. Barrier disruption promotes the passive diffusion of these lipophilic compounds, a process exacerbated by altered tight junctions, increased transepidermal water loss (TEWL), and heightened vascular permeability. Furthermore, inflammation-driven modifications in enzymatic activity may prolong anesthetic half-life, further increasing systemic exposure. Additional risk factors include the use of occlusive dressing techniques, prolonged application duration, and the concurrent use of multiple anesthetic agents. This review examines the pathophysiology of topical anesthetic absorption, the mechanisms underlying enhanced systemic exposure in the context of impaired epidermal integrity, and clinical strategies to mitigate toxicity. A nuanced understanding of these dynamics is crucial for optimizing the safe use of topical anesthetics, particularly in dermatologic and procedural care contexts.