Pharmacological intervention in the field of ototoxicity

Abstract

Modern research on ototoxicity goes back to the 1940s, when streptomycin was introduced into clinical practice. Today, aminoglycoside antibiotics and platinum-based chemotherapy, mainly cisplatin, are the most important drugs that damage the inner ear and cause hearing loss. The mode of drug administration as well as drug characteristics influence the likelihood that adequate monitoring of drug pharmacokinetics can be performed. It is not possible to predict the individual risk of treatment with an ototoxic drug, but identification of high-risk treatment protocols is important. There are many studies ongoing with the aim of discovering and developing drugs to treat different types of inner ear disorders. The mechanisms of ototoxicity and subsequent loss of hearing function have been mapped in various experimental models and have provided us with useful information for developing protective treatment. When an ototoxic lesion is established, restoration of hearing function becomes more difficult. For both aminoglycoside antibiotics and cisplatin, a large number of otoprotectors have been suggested. Systemic co-administration of an otoprotector would be the easiest approach to avoid ototoxicity in patients but it may negatively affect the intended pharmacotherapeutic aim of the ototoxic drug. New pharmacological formulations are being developed for local otoprotective treatment. This short review focuses on results from clinical reports on otoprotection in patients treated with aminoglycoside antibiotics and cisplatin. So far there is limited evidence for the safe management of otoprotection in patients. Further high-quality studies are needed to provide reliable data on the safety and effectiveness of pharmacological interventions to reduce drug-induced hearing loss.

Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology

“…As mentioned in the kidney section of this review, aminoglycoside antibiotics and anticancer platinum agents, most notably gentamicin and cisplatin, respectively, are known for their nephrotoxicity and also to induce irreversible hearing loss. While it cannot be disputed that these agents lead to ototoxicity, since evidence for the relevance of OCT2 in these processes has been presented in both rodents and gineau pigs, literature on humans on this topic is not abundant [ 169 ]. Additionally, conflicting evidence has been presented as to the localization of OCT2 in the inner ear structures in the experimental models used [ 40 , 170 ].…”

Drug‐Induced Ototoxicity: A Comprehensive Review and Reference Guide

“…It is also worth noting that certain ototoxic medications might even be otoprotective against other ototoxic medications. 29 For instance, aspirin has been explored for the potential to mitigate the effects of hearing loss induced by intravenous gentamicin. 30 The study found that 3% of patients receiving aspirin had evidence of hearing loss compared with 13% in the placebo group.…”

“…Although the mechanisms described previously are among those more commonly studied, other mechanisms of ototoxicity have yet to be investigated. It is also worth noting that certain ototoxic medications might even be otoprotective against other ototoxic medications 29 . For instance, aspirin has been explored for the potential to mitigate the effects of hearing loss induced by intravenous gentamicin 30 .…”

Current Strategies to Combat Cisplatin-Induced Ototoxicity

“…Although an extensive number of preclinical studies have explored protective interventions to reduce cisplatin-induced ototoxicity, there are no generally established clinical guidelines. The challenges for translation of preclinical to clinical trials are: (1) differences in morphology and physiology between the human cochlea and that of experimental animals (Laurell, 2019); (2) identification of ototoxic susceptible patients in that international standards among classification systems do not exist (Knight et al, 2017).…”