Intra-tympanic injections in the treatment of tinnitus

Coles, R. R. A.; Thompson, Adrian C.; 'Donoghue, Gerard M.O.

doi:10.1111/j.1365-2273.1992.tb01835.x

Cited by 35 publications

(24 citation statements)

References 8 publications

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“…Gentamicin is toxic to the sensory cells of the balance system and thereby suppresses the vertigo in these patients by partially ablating their vestibular system. There are also an increasing number of clinical reports related to the local application of glucocorticoids for acute hearing loss (9,10,11,12,13,14,15,16), glucocorticoids for Menière's disease (17,18,19,20) or for tinnitus (21,22,23,24,25). Other substances that have been tested in humans include local anaesthetics, neurotransmitters and neurotransmitter antagonists (26,27).…”

Section: Introductionmentioning

confidence: 99%

Local inner-ear drug delivery and pharmacokinetics

Salt

Plontke

2005

Drug Discovery Today

163

123

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SummaryA number of drugs are in widespread clinical use for the treatment of inner ear disorders by applying them directly to the inner ear. Many new substances and drug delivery systems specific to the inner ear are under development, and in some cases are undergoing evaluations in animal experiments and in clinical studies. The pharmacokinetics of drugs in the inner ear, however, is not well defined and the field is plagued by technical problems in obtaining pure samples of the inner ear fluids for analysis. Nevertheless, a basic understanding of the mechanisms of drug dispersal in the inner ear has emerged that facilitates the design and interpretation of future pharmacokinetic studies.

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Section: Introductionmentioning

confidence: 99%

Local inner-ear drug delivery and pharmacokinetics

Salt

Plontke

2005

Drug Discovery Today

163

123

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“…There are a growing number of clinical reports with regard to local treatments with corticosteroids in cases of acute hearing loss of various causes (Chandrasekhar, 2001;Gian-oli and Li, 2001;Gouveris et al, 2005;Ho et al, 2004;Lautermann et al, 2005;Lefebvre and Staecker, 2002;Plontke et al, 2005;Silverstein et al, 1996;Parnes et al, 1999), of Meniere's disease (Itoh and Sakata, 1991;Sennaroglu et al, 2001;Shea and Ge, 1996;Silverstein et al, 1998) and of tinnitus (Cesarani et al, 2002;Coles et al, 1992;Sakata et al, 1997;Shulman and Goldstein, 2000;Silverstein et al, 1996). In addition, a number of investigational drugs show promising results with respect to protection when locally applied to the RWM Chen et al, 2003b;Hight et al, 2003;Keithley et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

et al. 2006

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Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 μl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 μl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585 ± 527 μg/ml) was approximately twice that of dexamethasone phosphate (291 ± 369 μg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is, to a large extent, thought to be the result of the RWM permeability varying in different animals. It was not caused by substance analysis variations, because two different analytic methods were used and the concentration ratio between the two substances remained nearly constant across the experiments and because differences were apparent for the repeated samples obtained in each animal. Interpretation of the results using computer simulations allowed RWM permeability to be quantified. It also demonstrated, however, that cochlear clearance values could not be reliably obtained with microdialysis because of the significant contribution of dialysis to clearance. The observed interanimal variation, e.g., in RWM permeability, is likely to be clinically relevant to the local application of drugs in patients.

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“…However, intravenous injection of local anaesthetics carries too many risks for therapeutic use, and the alleviation has not been replicated with analogous but safer compounds, 64,65 or by other administration routes. 66 Drugs from several broad categories have been tested for eff ect on tinnitus. Tricyclic antidepressants and selective serotonin-reuptake inhibitors are not eff ective at reducing tinnitus, 67 but they might have a role in management of any concomitant psychological distress.…”

Section: Drug Treatmentsmentioning

confidence: 99%

Tinnitus

Baguley¹,

McFerran²,

Hall³

2013

The Lancet

1,066

911

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Tinnitus is a common medical symptom that can be debilitating. Risk factors include hearing loss, ototoxic medication, head injury, and depression. At presentation, the possibilities of otological disease, anxiety, and depression should be considered. No eff ective drug treatments are available, although much research is underway into mechanisms and possible treatments. Surgical intervention for any otological pathology associated with tinnitus might be eff ective for that condition, but the tinnitus can persist. Available treatments include hearing aids when hearing loss is identifi ed (even mild or unilateral), wide-band sound therapy, and counselling. Cognitive behavioural therapy (CBT) is indicated for some patients, but availability of tinnitus-specifi c CBT in the UK is poor. The evidence base is strongest for a combination of sound therapy and CBT-based counselling, although clinical trials are constrained by the heterogeneity of patients with tinnitus.

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Intra-tympanic injections in the treatment of tinnitus

Cited by 35 publications

References 8 publications

Local inner-ear drug delivery and pharmacokinetics

Local inner-ear drug delivery and pharmacokinetics

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

Tinnitus

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