Understanding drug ototoxicity: molecular insights for prevention and clinical management

  title={Understanding drug ototoxicity: molecular insights for prevention and clinical management},
  author={Joshua G. Yorgason and Jose N. Fayad and Federico Kalinec},
  journal={Expert Opinion on Drug Safety},
  pages={383 - 399}
Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and antimalarial medications. Because their benefits in combating certain life-threatening diseases often outweigh the risks, the use of these ototoxic drugs cannot simply be avoided. In this review, the authors discuss some of the most frequently used ototoxic drugs and what is currently known about the cell and molecular mechanisms underlying their… 

In vitro and in vivo models of drug ototoxicity: studying the mechanisms of a clinical problem

This review will discuss in vitro and in vivo models of ototoxicity highlighting recently published otot toxicity research and the strengths and limitations of different ototoxic models and what molecular insights have been gained from their application.

Assessment of Interventions to Prevent Drug-Induced Hearing Loss

Some of the common ototoxic drugs in clinical use, the potential o toprotective agents in clinical trials, methods for audiologic monitoring for ototoxicity and otoprotection, and the otot toxicity grading scales for use in clinical practice and inclinical trials are reviewed.

A Review of Cisplatin-Associated Ototoxicity.

The importance of a team-based approach to complement an audiological monitoring program in reducing any further loss in the quality of life of affected patients is highlighted, as there is currently no otoprotective agent routinely recommended for the prevention of cisplatin-associated ototoxicity.

Why is Drug-Induced Ototoxicity Still Not Preventable nor is it Treatable in 2019? - A Literature Review of Aminoglycoside and Cisplatin Ototoxicity

The clinical application would not only allow a more specific understanding of different mechanisms of iatrogenic oto-toxicity, but also allow new insights into targeted protective and post-lesional therapies.

Predicting the Need for a Tier II Ototoxicity Study From Early Renal Function Data

Biomarkers for nephrotoxicity in early tier I or tier II nonclinical IND-enabling studies should raise an inquiry as to the need to conduct a full auditory function assay early in the game to clear the pipeline with a safer candidate that has a higher probability of continued therapeutic compliance once approved for distribution.

Cisplatin-Associated Ototoxicity: A Review for the Health Professional

The need for a team-based approach to complement an audiological monitoring programme to mitigate any further loss in the quality of life of affected patients is highlighted, as there is currently no otoprotective agent recommended routinely for the prevention of cisplatin-associated ototoxicity.

Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use

Findings identify the inner hair cells as the most vulnerable element to AG treatment, indicating that gentamicin C1a and apramycin are promising bases for the development of clinically useful antibiotics.

Safety considerations with new antibacterial approaches for chronic bacterial prostatitis

Most antibacterial agents considered in this review have been administered off-label in the interest of patients, and their use requires particular caution, so readers should be warned of the limited published evidence supporting therapy for CBP with these agents.

An analysis of ototoxicity in children: Audiological detection, clinical practice and genetic susceptibility

This research has generated recommendations for several future studies and has informed the clinical management of patients with CF and identified gaps in the provision of ototoxicity monitoring services in the UK, especially due to the absence of nationally agreed guidelines.



Aminoglycoside ototoxicity

Understanding of the mechanisms of ototoxicity has improved and apoptotic pathways are clearly responsible for hair cell demise, and there are currently no recommendations for pretreatment or posttreatment therapies to attenuate otot toxicity associated with aminoglycoside antibiotics.

Ototoxicity Associated with Salicylates

The pathophysiology of toxicity may be related to biochemical and subsequent electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission and localised drug accumulation and vasoconstriction in auditory microvasculature, mediated by the antiprostaglandin activity of these agents.

A Cochlear Cell Line as an in vitro System for Drug Ototoxicity Screening

A conditionally immortalized organ of Corti-derived epithelial cell line is reported, which shows evidence of activation of apoptosis when exposed to known ototoxic drugs.

Recent Advances in Understanding Aminoglycoside Ototoxicity and Its Prevention

A hypothesis of the mechanism of toxicity is reviewed, possible causes underlying the gradient in base-to-apex sensitivity of outer hair cells are discussed, and recent results on the adult mouse as a new animal model of aminoglycoside ototoxicity and its prevention are presented.

Aminoglycoside-induced ototoxicity.

Ototoxicity Induced by Gentamicin and Furosemide

Clinicians need to be aware of the synergistic potential of ototoxic medications and the cumulative dose and duration of aminoglycoside therapy are more important than serum concentrations.

The aminoglycosides.

  • A. Whelton
  • Medicine
    Clinical orthopaedics and related research
  • 1984
Aminoglycoside antibiotics continue to be indispensable in the management of complex aerobic gram-negative infections and are ideally suited for inclusion in polymethylmethacrylate bone cements as a delivery system for prevention or treatment of orthopedic surgical infections.

Temporal bone histopathology of cisplatin ototoxicity.

This report presents four cases of cisplatin ototoxicity in patients from whom temporal bone specimens with minimal post-mortem autolysis were obtained at autopsy and Histopathologic changes included loss of inner and outer hair cells in the basal turn of the cochlea, degeneration of the stria vascularis, and a significant decrease in spiral ganglion cells predominantly in the upper turns.

Ototoxicity of vancomycin: an experimental study in guinea pigs.

Treatment with moderate doses of V comparable to clinical conditions does not exhibit a specific ototoxicity as compared to the aminoglycosides, and Renal damage could be excluded by histological examination of the kidneys and estimation of creatinine in serum.

Molecular mechanisms of drug-induced hearing loss