In most cases, tinnitus pitch or frequency range is between 5 kHz and 10 kHz, and loudness between 5 and 15 dB above the hearing threshold.Another relevant parameter of tinnitus is residual inhibition, the temporary suppression or disappearance of tinnitus following a period of masking. The degree of residual inhibition may indicate how effective tinnitus maskers would be as a treatment modality.An assessment of hyperacusis, a frequent accompaniment of tinnitus, may also be made. Hyperacusis is related to negative reactions to sound and can take many forms. One associated parameter that can be measured is Loudness Discomfort Level (LDL) in dB, the subjective level of acute discomfort at specified frequencies over the frequency range of hearing. This defines a dynamic range between the hearing threshold at that frequency and the loudness discomfort level. A compressed dynamic range over a particular frequency range can be associated with hyperacusis. Normal hearing threshold is generally defined as 0–20 decibels (dB). Normal loudness discomfort levels are 85–90+ dB, with some authorities citing 100 dB. A dynamic range of 55 dB or less is indicative of hyperacusis. Severity
The condition is often rated on a scale from "slight" to "severe" according to the effects it has, such as interference with sleep, quiet activities and normal daily activities.Assessment of psychological processes related to tinnitus involves measurement of tinnitus severity and distress (i.e., nature and extent of tinnitus-related problems), measured subjectively by validated self-report tinnitus questionnaires.
Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine (in descending order of inhibition) due to their effects on the CYP3A4 enzyme.Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations. Mechanism of action
Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and T-type calcium channels, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity). It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant topiramate). It is also known to modulate GABAergic and glutamatergic neurotransmission. Pharmacokinetics
Absorption
Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Bioavailability is close to 100% and food has no effect on the bioavailability of zonisamide but may affect the rate of absorption. Metabolism
Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5, to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring. History
Zonisamide was discovered by Uno and colleagues in 1972 and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan. It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai Co., Ltd. in 2004.