Abstract
The modern era of evidence-based ototoxicity emerged in the 1940s following the discovery of aminoglycosides and their ototoxic side effects. New classes of ototoxins have been identified in subsequent decades, notably loop diuretics, antineoplastic drugs, and metal chelators. Ototoxic drugs are frequently nephrotoxic, as both organs regulate fluid and ion composition. The mechanisms of ototoxicity are as diverse as the pharmacological properties of each ototoxin, though the generation of toxic levels of reactive oxygen species appears to be a common denominator. As mechanisms of cytotoxicity for each ototoxin continue to be elucidated, a new frontier in ototoxicity is emerging: How do ototoxins cross the blood-labyrinth barrier that tightly regulates the composition of the inner ear fluids? Increased knowledge of the mechanisms by which systemic ototoxins are trafficked across the blood-labyrinth barrier into the inner ear is critical to developing new pharmacotherapeutic agents that target the blood-labyrinth barrier to prevent trafficking of ototoxic drugs and their cytotoxic sequelae.