Ототоксичность: причины, симптомы и профилактика поражения слуха.

Ototoxicity is the property of being toxic to the ear (oto ), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and temporary, or irreversible and permanent. It has been recognized since the 19th century. There are many well known ototoxic drugs used in clinical situations, and they are prescribed, despite the risk of hearing disorders, for very serious health conditions. Ototoxic drugs include antibiotics (such as gentamicin, streptomycin, tobramycin), loop diuretics (such as furosemide), and platinum based chemotherapy agents (such as cisplatin and carboplatin). A number of nonsteroidal anti inflammatory drugs (NSAIDS) have also been shown to be ototoxic. This can result in sensorineural hearing loss, dysequilibrium, or both. Some environmental and occupational chemicals have also been shown to affect the auditory system and interact with noise.

Symptoms of ototoxicity include partial or profound hearing loss, vertigo, and tinnitus. Ototoxicity typically results when the inner ear is poisoned by medication that damages the cochlea, vestibule, semi circular canals, or the auditory/ vestibulocochlear nerve. The damaged structure then produces the symptoms the patient presents with. Ototoxicity in the cochlea may cause hearing loss of the high frequency pitch ranges or complete deafness, or losses at points between. It may present with bilaterally symmetrical symptoms, or asymmetrically, with one ear developing the condition after the other or not at all. It may result from antibiotic binding to NMDA receptors in the cochlea and damaging neurons through excitotoxicity. Aminoglycoside induced production of reactive oxygen species may also injure cells of the cochlea. Once daily dosing and co administration of N acetylcysteine may protect against aminoglycoside induced ototoxicity. The anti bacterial activity of aminoglycoside compounds is due to inhibition of ribosome function and these compounds similarly inhibit protein synthesis by mitochondrial ribosomes because mitochondria evolved from a bacterial ancestor. Consequently, aminoglycoside effects on production of reactive oxygen species as well as dysregulation of cellular calcium ion homeostasis may result from disruption of mitochondrial function. Ototoxicity of gentamicin can be exploited to treat some individuals with Ménière's disease by destroying the inner ear, which stops the vertigo attacks but causes permanent deafness. Due to the effects on mitochondria, certain inherited mitochondrial disorders result in increased sensitivity to the toxic effects of aminoglycosides. Macrolide antibiotics, including erythromycin, are associated with reversible ototoxic effects. The related compound ethacrynic acid has a higher association with ototoxicity, and is therefore used only in patients with sulfa allergies. Diuretics are thought to alter the ionic gradient within the stria vascularis. Bumetanide confers a decreased risk of ototoxicity compared to furosemide.

Platinum containing chemotherapeutic agents, including cisplatin and carboplatin, are associated with cochleotoxicity characterized by progressive, high frequency hearing loss with or without tinnitus (ringing in the ears). Ototoxicity is less frequently seen with the related compound oxaliplatin. The severity of cisplatin induced ototoxicity is dependent upon the cumulative dose administered and the age of the patient, with young children being most susceptible. The exact mechanism of cisplatin ototoxicity is not known. The drug is understood to damage multiple regions of the cochlea, causing the death of outer hair cells, as well as damage to the spiral ganglion neurons and cells of the stria vascularis. Long term retention of cisplatin in the cochlea may contribute to the drug's cochleotoxic potential. Once inside the cochlea, cisplatin has been proposed to cause cellular toxicity through a number of different mechanisms, including through the production of reactive oxygen species. The decreased incidence of oxaliplatin ototoxicity has been attributed to decreased uptake of the drug by cells of the cochlea. The vinca alkaloids, including vincristine, are also associated with reversible ototoxicity. The ototoxicity of chlorhexidine was further confirmed by studies with animal models. However the link between erectile dysfunction medications and hearing loss remains uncertain. Previous noise exposure has not been found to potentiate ototoxic hearing loss. The American Academy of Audiology includes in their position statement that exposure to noise at the same time as aminoglycosides may exacerbate ototoxicity. The American Academy of Audiology recommends people being treated with ototoxic chemotherapeutics avoid excessive noise levels during treatment and for several months following cessation of treatment. Opiates in combination with excessive noise levels may also have an additive effect on ototoxic hearing loss.

No specific treatment may be available, but withdrawal of the ototoxic drug may be warranted when the consequences of doing so are less severe than those of the ototoxicity. It is difficult to distinguish between nerve damage and structural damage due to similarity of the symptoms. Diagnosis of ototoxicity typically results from ruling out all other possible sources of hearing loss and is often the catchall explanation for the symptoms. Treatment options vary depending on the patient and the diagnosis. Some patients experience only temporary symptoms that do not require drastic treatment while others can be treated with medication. Physical therapy may prove useful for regaining balance and walking abilities. Cochlear implants are sometimes an option to restore hearing. Such treatments are typically taken to comfort the patient, not to cure the disease or damage caused by ototoxicity. There is no cure or restoration capability if the damage becomes permanent, although cochlear nerve terminal regeneration has been observed in chickens, which suggests that there may be a way to accomplish this in humans.