Salicylate ototoxicity in patients with rheumatoid arthritis: a controlled study.

Halla, James T.; Hardin, Joe G.

doi:10.1136/ard.47.2.134

Cited by 47 publications

(33 citation statements)

References 6 publications

(3 reference statements)

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“…Mongan et al (1965) (Myers et al, 1973). More recently, Halla & Hardin (1988) reported that tinnitus and deafness could occur below these threshold levels.…”

Section: Introductionmentioning

confidence: 99%

Concentration‐response relationships for salicylate‐induced ototoxicity in normal volunteers.

Day

Graham

Bieri

et al. 1989

Brit J Clinical Pharma

103

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1 Ototoxicity is a common and troublesome side-effect of high-dose aspirin treatment but there has been little previous study of the relationships between the degree of ototoxicity and the plasma concentrations of salicylate. 2 In order to investigate the relationships between aspirin dose, total and unbound plasma salicylate concentrations and ototoxicity, eight normal volunteers were dosed with aspirin 1.95, 3.25, 4.55 and 5.85 g day-1 for 1 week at each dose level, the doses being administered in random order and double-blind, 2 weeks apart. 3 Ototoxic effects measured were hearing loss in decibels (dB) over six frequencies and tinnitus intensity, estimated both by electronic matching and a fixed interval scale (FIS). Measurements were taken after steady-state concentrations of salicylate had been achieved. 4 Total and unbound plasma salicylate concentrations increased disproportionately with increasing daily doses of aspirin. The increase in the unbound salicylate was relatively greater since the percentage of salicylate unbound in plasma increased over the dose range investigated from a mean of 3.9% to 10.4%. 5 Hearing loss and tinnitus intensity increased progressively with the aspirin dosage and increasing concentrations of total and unbound plasma salicylate concentrations. These ototoxic symptoms were observed at lower concentrations of total salicylate than previously reported. 6 There was a linear relationship between hearing loss and unbound salicylate concentations. 7 Further work is required to test the hypothesis that unbound plasma salicylate concentration is a better predictor of salicylate-induced ototoxicity than total plasma salicylate concentration.

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“…Mongan et al (1965) (Myers et al, 1973). More recently, Halla & Hardin (1988) reported that tinnitus and deafness could occur below these threshold levels.…”

Section: Introductionmentioning

confidence: 99%

Concentration‐response relationships for salicylate‐induced ototoxicity in normal volunteers.

Day

Graham

Bieri

et al. 1989

Brit J Clinical Pharma

103

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“…Salicylate, a widely used anti-inflammatory drug, has been shown to induce tinnitus [5,6,7,8,36,37,38]. In this work, we performed experiments with salicylate at a concentration of 350 mg/kg based on the literature [4,39,40,41,42,43].…”

Section: Discussionmentioning

confidence: 99%

Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus

Zhang

Xue

Liu

et al. 2014

Cell Physiol Biochem

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Background: This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus. Methods: C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons. Results: The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7^th d and decreased on the 9^th and 10^th d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days. Conclusion: This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus.

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“…The two waves are thought to interact and create a sound wave that is of the frequency 2f1 À f2, which travels toward the input direction (Dalhoff et al 2007). The resultant wave travels through the cochlea, out of the oval window, and through the middle ear where it is emitted from the tympanic membrane as a noise (Hall 2000). The noise can be averaged and the intensity defined for pretest and postdose evaluations.…”

Section: Distortion Product Otoacoustic Emissionsmentioning

confidence: 99%

The Safety Pharmacology of Auditory Function

Abernathy

2015

Principles of Safety Pharmacology

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Safety pharmacology satisfies a key requirement in the process of drug development. Safety pharmacology studies are required to assess the impact of a new chemical entity (NCE) or biotechnology-derived product for human use on vital systems, such as those subserving auditory function. Safety pharmacology studies accordingly are defined as those studies that investigate the potential undesirable effects of a substance on auditory functions in relation to exposure in and above the therapeutic range. Auditory safety studies should be designed with the primary objective of determining how administration of a compound influences normal hearing. If an effect on hearing is identified, then it is necessary to determine through histopathology the underlying mechanism for the observed hearing loss. Since the auditory system contains a heterogeneous mixture of structural and cellular components that are organized in a very complex and integrated manner, it is necessary to clearly identify the underlying primary mechanism or target of the new chemical entity that produced the hearing loss. This chapter will highlight major components of auditory function with regard to potential opportunities for drug interaction. Aspects of designing ototoxicity studies will be discussed with an emphasis on standards deemed necessary by the US Food and Drug Administration. Additionally, classes of ototoxic compounds and their proposed mechanisms of action are described in depth.

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Salicylate ototoxicity in patients with rheumatoid arthritis: a controlled study.

Cited by 47 publications

References 6 publications

Concentration‐response relationships for salicylate‐induced ototoxicity in normal volunteers.

Concentration‐response relationships for salicylate‐induced ototoxicity in normal volunteers.

Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus

The Safety Pharmacology of Auditory Function

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