[e-farmacos] Ototoxicidad poracido mefenamico (cont.)

["Morgado, Cecilia" <cmorgado@ispch.cl>]

Hola,

Dos referencias para J Carlos Piola sobre ototoxicidad y acido mefenamico:

1: J Neurosci. 2003 May 1;23(9):3944-52. Links:
Salicylate induces tinnitus through activation of cochlear NMDA receptors.
Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL. 
Institut National de la Sante et de la Recherche Medicale UR-254, Laboratoire de Neurobiologie de l'Audition-Plasticite Synaptique, Faculte de Medecine, Universite de Montpellier 1, 34090 Montpellier, France.

Salicylate, the active component of aspirin, is known to induce tinnitus. 
However, the site and the mechanism of generation of tinnitus induced by 
salicylate remains unclear. Here, we developed a behavioral procedure to 
measure tinnitus in rats. The behavioral model was based on an active 
avoidance paradigm in which rats had to display a motor task (i.e., to jump 
on a climbing pole when hearing a sound). Giving salicylate led to a decrease in the percentage of correct responses (score) and a drastic increase in the number of false positive responses (i.e., animals execute the motor task during a silent period). Presentation of the sound at a constant perceptive level prevents decrease of the score, leading to the proposal that score is related to hearing performance. In contrast, the increase of false positive responses remained unchanged. In fact, animals behaved as if they hear a sound, indicating that they are experiencing tinnitus. Mefenamate in place of salicylate also increased the number of false positive responses, suggesting that salicylate-induced tinnitus is related to an inhibition of cyclooxygenase. One physiological basis of salicylate ototoxicity is likely to originate from altered arachidonic acid metabolism. Because arachidonic acid potentiates NMDA receptor currents, we tested the involvement of cochlear NMDA receptors in the occurrence of tinnitus. Application of NMDA antagonists into the perilymphatic fluids of the cochlea blocked the increase in pole-jumping behavior induced by salicylate, suggesting that salicylate induces tinnitus through activation of cochlear NMDA receptors.

DRUGDEX DRUG EVALUATIONS (última ediión, vence 31.12.06)

MEFENAMIC ACID
ADVERSE REACTIONS  OTIC 
A) Ear and auditory finding 
1) Hyperacusis has occurred with mefenamic acid therapy.
B) Hyperacusis 
1) Summary 
a) Hyperacusis occurred in a 55-year-old male receiving mefenamic acid 500 
milligrams three times/day. After 3 days of therapy, the patient developed a 
severe HYPERSENSITIVITY TO NOISE with less severe tinnitus and vertigo. 
Following discontinuation of mefenamic acid, the patient's symptoms resolved 
within 2 days (Morris & Fletcher, 1986)

Referencia
Morris DL & Fletcher A: Hyperacusis after treatment with mefanamic acid. Br 
Med J 1986; 293:823.

Dra. QF. Cecilia Morgado Cadiz
Jefa Centro Nacional de Informacion de
Medicamentos Y Farmacovigilancia -CENIMEF
Fono 56 2 239 87 69- Fax 56 2 239 87 60
cmorgado@ispch.cl
(Chile)