WHAT IS OTOTOXICITY

WHAT IS OTOTOXICITY

By Larry Bailey May 2017

“OTO means EAR;
TOXICITY means POISONING”

Ototoxicity is, quite simply, ear poisoning, which results from exposure to drugs or chemicals that damage the inner ear or the vestibulo-cochlear nerve (the nerve sending balance and hearing information from the inner ear to the brain). Because the inner ear is involved in both hearing and balance, ototoxicity can result in disturbances of either or both of these senses.

Neurotoxicity is Poisoning of the brain

The parts of the brain that receive hearing and balance information from the inner ear can also be affected by poison, but this is not technically considered ototoxicity. The occurrence and degree of inner ear poisoning depends upon the drug involved as well as other factors such as heredity. Ototoxicity can be temporary or permanent. The effect of certain drugs is often temporary, while other drugs typically produce permanent changes to the ear. Some drugs can cause either temporary or permanent problems. It is important to note here that the broad majority of people who experience ototoxicity have a temporary or reversible form that does not result in a major or long-term disruption in their lives.

Cochleotoxicity is Poisoning of the Cochlea

With Cochleotoxicity, hearing loss or the start or tinnitus (ringing in the ears) can occur through damage to the cochlea or the cochlear branch of the vestibulo-cochlear nerve.

Vestibularototoxicity or vestibulo-toxicity is Poisoning that affects the balance organs or the vestibular branch of the vestibulo-cochlear nerve.

It is important to note that no drug is known to cause Ménière’s disease, benign paroxysmal positional vertigo, or any other vestibular disorder causing fluctuating function.

How Common is Ototoxicity?

No one knows how many people suffer from ototoxicity each year or the percentage of vestibular disorders caused by ototoxicity. What is known is that when permanent and extensive ototoxicity occurs, the effects can take a terrible toll on a person’s ability to function

What Substances Can Cause Ototoxicity?

Ototoxicity has been found to be a problem with aspirin and quinine, antibiotic streptomycin, recently with some anti-cancer drugs. Many chemicals have ototoxic potential, including over-the-counter drugs, prescription medications, and environmental chemicals.
Scientific studies are required to confirm whether a drug is ototoxic. Unfortunately, such research often involves years and years of study. When assessing the safety of a drug prior to releasing it on the market, the U.S. Food and Drug Administration does not require testing of inner ear function or examination of the inner ear structures. This is one reason it is almost impossible to say with confidence how many and which drugs cause ototoxicity and how many or which people are affected by it.

The information below includes substances thought to cause ototoxicity. The discussion is incomplete because of the limited research thus far.

These are only suggested to be Ototoxic:

• Aspirin and quinine Aspirin (acetylsalicylic acid, ASA) and quinine are well known to cause temporary ototoxicity resulting in tinnitus. They may also reduce hearing, particularly when
given at high doses.
• Quinine products can also temporarily reduce balance ability. Once aspirin or quinine is stopped, the ototoxicity generally disappears. Some quinine products include:
• Chloroquine
• Quinidine
• Quinine (including Q-vel)
• Tonic water
• Loop diuretics are a specific family of “water pills” that is known to occasionally cause temporary ototoxicity. These drugs cause ringing in the ears or decreased hearing that
reverses when the drug is stopped.

An increased probability of ototoxicity is thought to occur with loop diuretics when they are administered during the same time period that an aminoglycoside antibiotic (see next
section) is given.

The loop diuretics include:
• bumetanide (Bumex)
• ethacrynic acid (Edecrin)
• furosemide (Lasix)
• torsemide (Demadex)
• Hydrochlorothiazide (HCTZ) and Maxide—diuretics commonly prescribed to people with Ménière’s disease or other forms of endolymphatic hydrops—are not loop diuretics.
• Aminoglycoside antibiotics All members of the aminoglycoside antibiotic family are well known for their potential to cause permanent ototoxicity.
• amikacin
• netilmicin
• dihydrostreptomycin
• ribostamycin
• gentamicin
• streptomycin
• kanamycin
• tobramycin
• neomycin
• Anti-neoplastics (anti-cancer drugs)
Anti-cancer drugs work by killing cancer cells. Unfortunately some can also damage or kill cells elsewhere in the body, including the ears.
• Cisplatin is well known to cause massive and permanent hearing loss.
• Carboplatin is also known to be ototoxic.

Environmental chemicals

Environmental chemicals have long been implicated in ototoxicity. Little research has been done to substantiate their precise effect on ears, but most are associated with hearing disturbances that may be permanent. In addition, mercury has also been linked to permanent balance problems.

These include:

• butyl nitrite
• mercury
• carbon disulfide
• styrene
• carbon monoxide
• tin
• hexane
• toluene
• lead
• trichloroethylene
• manganese
• xylene


Damage

Two areas can be damaged or destroyed through ototoxicity: the hair cells within the inner ear, and the vestibulo-cochlear nerve that links the inner ear to the brain. When damage occurs, any degree and combination of hearing loss and balance disruption are possible depending upon the part(s) affected.
Hair cells are located in both the cochlea and the vestibular areas of the inner ear. They are composed of a cell body with a hair-like attachment. When these “hairs” are normally bent with sound vibrations or movement, they send electrical signals to the brain about hearing or balance function. In ototoxicity, these hairs can be damaged to the point that they no longer stand up, thus reducing the auditory and/or balance signals sent to the brain.

Symptoms

Cochleotoxicity symptoms range from mild tinnitus to total hearing loss, depending upon each person and the form and level of exposure to the ototoxin. They can include one-sided or two-sided hearing loss and constant or fluctuating tinnitus.

Vestibulotoxicity symptoms range from mild imbalance to total incapacitation. Symptoms of a vestibular or balance function loss depend upon the degree of damage, if the damage occurred rapidly or slowly, if it’s one-sided or two-sided, and how long ago the damage occurred. A slow one-sided loss might not produce any symptoms, while a rapid loss could produce enough vertigo, vomiting, and nystagmus (eye jerking), to keep a person in bed for days. Most of the time, the symptoms slowly pass, allowing a person to return to normal activities.

A two-sided loss in vestibulotoxicity typically causes headache, a feeling of ear fullness, imbalance to the point of being unable to walk, and a bouncing and blurring of vision (oscillopsia) rather than intense vertigo, vomiting, and nystagmus. It also tends to produce inability to tolerate head movement, a wide-based gait (walking with the legs farther apart than usual), and difficulty walking in the dark, unsteadiness , lightheaded, and significant fatigue. If the damage is severe, symptoms such as oscillopsia and problems with walking in the dark or with the eyes closed will not diminish with time.

Ototoxicity Diagnosed

The diagnosis is based upon the patient’s history, symptoms, and test results. Some of the tests that may be used to determine how much hearing or balance function have been lost involve the vestibular auto-rotation test (VAT), vestibulo-ocular reflex testing equipment (VORTEQ), electronystagmography (ENG), computerized dynamic posturography (CDP), rotary chair (SHAT), head-shaking, electrocochleography (EcoG), auditory brainstem response (ABR), otoacoustic emissions, pure tone audiometry, speech discrimination, and most other tests often used to identify and quantify inner ear problems.

Treatment

See an Audiologist, ENT, or Physician

Please Note that ongoing related research is working on prevention and treatment. Chemicals are being evaluated for their ability to prevent ototoxicity. Investigators are currently studying methods of hair-cell and nerve-cell regeneration. In the distant future, it may be possible to stimulate the ear into growing replacement hair cells and to repair damaged nerve fibers. We will have to wait and see if that happens?

References
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