Ototoxicity-the Hidden Menace. Part
I: Lives in Upheaval Neil G. Bauman, Ph.D.
9. Avoid taking multiple ototoxic drugs at the same time.
EDITOR'S NOTE - Although
most audiologists are familiar with ototoxicity, this article is an in-depth, patient-friendly review of the possible signs, symptoms,
outcomes and issues. This article is written
with the patient as the intended audience.
"Lynn's" passion was flying. She loved her
job as a flight attendant. One day she noticed an ingrown toenail.
Within a few days it became infected. The Gentamicinl her doctor prescribed killed the infection. It also killed the
balance system in her ears. Ever since that fateful day in 1994, Lynn has not been able to
work or fly. Without warning, an ototoxic drug turned her world upside down.
An ototoxic drug flipped
"Ruby's" life upside down too. She explains: "I cannot drive any more. I had to quit
my job as it was an hour's drive away. My mental status is now "foggy" at
best. I cannot walk in the dark. My life has changed drastically."
"Bert" lost much of his hearing after
taking Doxycycline for a urinary
tract infection. "Eunice" told me that just taking the Amitriptyline her doctor prescribed for
her resulted in "screaming tinnitus."
"Jonathan" described how he lost hearing
in one ear after he took a course of Erythromycin.
In addition,
he experienced hyperacusis, balance problems and "horrific bilateral tinnitus."
"Jonathan's" condition appears to be permanent—as this happened five years ago.
Peggy told me, "I was given Atenolol for some little irregular
heart beats. Within a few days my perfectly normal ears started to give me all kinds of noise,
roaring and muffledness. Within a week, I woke up one morning stone cold deaf
in one ear."
In an email to me, "Sam" told how his
doctor had prescribed an ointment containing Tobramycin for a sty on his left
eyelid. He wrote, "I started using the cream on my left eyelid on Tuesday. At
8:30 the next morning, I lost the hearing in my left ear." In "Sam's" case,
the Tobramycin apparently caused
sudden hearing loss just 19 hours later—and this was only from using an
ointment on his eyelid!
I wish I could say these are only a few isolated
incidents, but I'd be lying if I did so. The truth is—side effects of
ototoxic drugs are more common than people (doctor's included) imagine. Each year, the
side effects of ototoxic drugs disrupt millions of people's lives and leave a trail of
upheaval in their wake.
It is not just drugs
taken for chemotherapy and life-threatening infections that cause ototoxic
reactions, but the little unexpected everyday things too—an ingrown toenail, a sty on your eye, an irregular heartbeat, high
blood pressure, and on and on it goes. Whether
the ototoxic side effects result from taking an ototoxic drug for a
life-threatening malady or for a
relatively minor disorder, the results are the same—lives turned upside down.
Scary? You bet it is. Obviously, it's about time we
became aware of what drugs are doing to our ears and learn to make wise
decisions regarding them.
What Is Ototoxicity?
To many doctors, ototoxicity just means hearing loss
or tinnitus. Others consider only drug side effects that affect the inner ear as being
ototoxic. However, Stedman's Medical Dictionagil defines ototoxicity as
the "property of being injurious to the ear." Therefore, any side
effect of a drug that damages our ears in any way is ototoxic whether it
damages the outer, middle or inner ear.
How Common Are Ototoxic Side Effects?
How common are ototoxic side effects? The short
answer is, "No one really knows." We apparently only see (and
record) the tip of the iceberg. For extremely ototoxic drugs such as Cisplatin (used in the treatment of
cancer), virtually everyone that takes this drug ends up with hearing loss.
According to some researchers, not a single person escapes its ravages-100% of the
people taking Cisplatin damage their
ears.5 The resulting hearing loss "is usually irreversible (permanent). "8
Another very ototoxic class of drugs are the
Aminoglycoside antibiotics. Researchers estimate that between one and four million Americans receive
Aminoglycoside antibiotics (such as Gentamicin, Neomycin, Tobramycin) each
year.7 According to one study, a person has a 25-30% chance of incurring hearing loss from taking
any of the Aminoglycosides.9 Another study pegs the figure at 63%.5
This means that between 250,000 and 1,200,000 people
(and maybe as high as 2,520,000 people) in the USA incur hearing losses each year
from taking just this one class of drugs. Add to these figures the untold numbers of
people who experience other side effects from taking these same drugs—such as
tinnitus, dizziness, vertigo and numerous other cochlear and vestibular (balance)
problems—and you have a figure of alarming proportions. It is even more alarming when you realize we are just
talking about a handful of ototoxic drugs in
2 of the more than 150 classes of ototoxic drugs!
Ototoxic Drugs
are Everywhere!
There are at
least 743 drugs that are known to be ototoxic.4 Here are
just 84 of them. This
gives an inkling of just
how all-pervading ototoxic substances are in the medications we take without having a
clue that these drugs may be harming our ears.
·
ACE inhibitors such as Enalapril (Vasotec),2 Moexipril (Univasc), Ramipril (Altace)
·
Acetic acids such as Diclofenac (Voltaren), Etodolac (Lodine), Indomethacin (Indocin), Ketorolac (Toradol)
·
Alpha blockers such as Doxazosin (Cardura)
·
Aminoglycosides such as Amikacin (Amikin), Gentamicin (Garamycin), Kanamycin (Kantrex), Neomycin (Neosporin), Netilmicin (Netromycin), Streptomycin, Tobramycin (Tobradex)
·
Angiotensin-2-receptor antagonists such as Eprosartan (Teveten), Irbesartan (Avapro)
·
Anti-arrhythmic drugs such as Flecainide
(Tambocor), Propafenone (Rythmol), Quinidine (Cardioquin), Tocainide (Tonocard)
·
Anti-cancer drugs such as Buserelin
(Suprefact), Carboplatin (Paraplatin), Cisplatin (Platinol), Vinblastine (Velban), Vincristine (Oncovin)
·
Anti-convulsant drugs such as Carbamazepine
(Tegretol), Divalproex (Depakote), Gabapentin (Neurontin), Tiagabine (Gabitril), Valproic acid (Depakene)
·
Anti-malarial drugs such as Chloroquine
(Aralen), Mefloquine (Lariam), Quinine (Legatrin)
·
Anti-retroviral protease inhibitors such as Cidofovir (Vistide), Ganciclovir (Cytovene), Ritonavir (Norvir)
·
Benzodiazepines such as Diazepam (Valium), Estazolam (ProSom), Midazolam (Versed)
·
Beta-blockers such as Atenolol (Tenormin), Betaxolol (Betoptic), Metoprolol (Lopressor)
·
Bicyclic anti-depressants such as Venlafaxine
(Effexor)
·
Calcium-channel-blockers such as Diltiazem
(Cardizem), Nifedipine (Adalat), Nisoldipine (Sular)
·
Cox-2 inhibitors such as Celecoxib (Celebrex), Rofecoxib (Vioxx)
·
Hl-blockers such as Cetirizine (Zyrtec), Fexofenadine (Allegra)
·
Immunosuppressant drugs
such as Cyclosporine (Neoral), Muromonab-CD3 (Orthoclone OKT3), Tacrolimus (Prograf)
·
Loop diuretics such as Ethacrynic
acid (Edecrin), Furosemide (Lasix), Torsemide (Demadex)
·
Macrolide antibiotics such as Clarithromycin (Biaxin), Erythromycin (Eryc)
·
Opiate agonist drugs such as Codeine
(Codeine Contin), Hydrocodone (Vicodin), Tramadol (Ultram)
·
Propionic acids such as Flurbiprofen
(Ansaid), Ibuprofen (Motrin), Naproxen (Anaprox)
·
Proton pump inhibitors such as Esomeprazole
(Nexium), Lansoprazole (Prevacid), Rabeprazole (Aciphex)
·
Quinolones such as Ciprofloxacin (Cipro), Ofloxacin (Floxin), Trovafloxacin (Trovan)
·
Salicylates such as Aspirin,
Mesalamine (Asacol), Olanzapine (Zyprexa)
·
Selective serotonin reuptake inhibitors (SSRIs) such as Fluoxetine (Prozac), Fluvoxamine (Luvox), Sertraline (Zo/oft)
·
Serotonin-receptor agonists such as Almotriptan
(Axert), Naratriptan (Amerge), Sumatriptan (Imitrex)
·
Thiazides such as Bendroflumethiazide
(Corzide), Indapamide (Lozol)
·
Tricyclic anti-depressants such as Amitriptyline
(Elavil), Clomipramine (Anafranil)
Ototoxic Side Effects
Ototoxic side effects can damage our ears in many
different ways. You may experience one, several or no side effects from taking any
given drug. The average ototoxic drug exhibits about 3.5 ototoxic symptoms.4 Here are a number of
the ototoxic side effects you could experience.
When you know which ototoxic side effects can
occur, you can watch for them. If they do occur, immediately contact your physician, stop
taking the offending drug (with your doctor's consent—of course) to try to limit the
damage to your ears.
1. Cochlear side effects
·
Tinnitus: Tinnitus, commonly
called "ringing in the ears," is the number one indicator that you may be
damaging your ears from an ototoxic drug. At least 447
drugs are
known to cause tinnitus.4 Tinnitus can manifest
itself as a wide variety
of sounds. It may be a ringing, roaring, beating,
clicking, banging, buzzing, hissing, humming, blowing, chirping, clanging, sizzling, whooshing,
rumbling, whistling or dreadful shrieking noise in your head. It may also sound
like rushing
water, radio static, breaking glass, bells ringing,
owls hooting or chainsaws running.3
·
Hearing loss: More than 230 drugs are
known to cause hearing loss.4 Hearing loss can range from mild to profound and may be
temporary or permanent. One of the insidious things about ototoxic drugs is they generally first destroy
hearing in the very high frequencies which are not normally tested (those above
8,000 Hz). Thus, you're not even aware you are losing your hearing until it is too
late to do anything about it.
·
Distorted hearing: Some drugs, instead of
causing hearing loss (or in addition to causing hearing loss), cause hearing to be
distorted so we do not understand some (or much) of what we are hearing.
·
Hyperacusis: Hyperacusis is a
condition where normal sounds are perceived as being much too loud. It
is as though the body's internal volume control is stuck on "high." At
least 38 drugs can cause this condition.4
·
Feelings of fullness in
your ears: You can experience this feeling for a few reasons. One, because
your ears really are blocked by a middle ear infection or by earwax. Two, because
your ears feel "blocked"
because of sudden hearing loss. Three, exposure to loud sounds can result in a
feeling of "fullness" too.
·
Auditory hallucinations: At least 8 drugs can
cause you to hear phantom sounds—voices and music that are not there. Another 165 drugs can cause
hallucinations, some of which may be of the auditory variety.4 Most of these hallucinations seem to
be the result of a damaged auditory system rather than the effects of a mental
illness.
2. Vestibular Side Effects
·
Dizziness: Dizziness is the most
common ototoxic symptom. At least 588 drugs have this ototoxic side effect.4
·
Vertigo: Vertigo is the perception
of movement (normally a spinning sensation) when the body is really not moving. At least 432
drugs are known to cause vertigo.4
·
Ataxia: Ataxia is the loss of
your ability to coordinate your muscles properly and can be a result of a
damaged vestibular system. As a result you may walk with a staggering gait, just as
though you were drunk. At least 288 drugs can cause this side effect.4
·
Nystagmus: Nystagmus is abnormal rapid rhythmic back-and-forth involuntary eye movement, usually
from side to side. Although technically an eye problem, it fundamentally is the
result of a damaged vestibular system. At least 102 drugs can cause this side effect.4
·
Labyrinthitis: Labyrinthitis is a
catch-all term that simply means something is wrong in your inner ear
(cochlear and vestibular systems).
·
Loss of
balance/equilibrium disorder: Some drugs cause a person to lose their balance. These terms too,
are mostly catch-alls for various kinds of balance conditions.
·
Oscillopsia: Oscillopsia is
"bouncing vision." This is the result of damage to the vestibular system such
that it no longer works together as the vestibulo-ocular reflex. Oscillopsia can
result when your vestibular system in both ears is severely damaged.
·
Emotional problems: When you lose much of
your sense of balance, emotional problems such as anxiety, frustration, anger and
depression can surface.7 Your feelings of self-confidence and self-esteem may plummet.
·
Fatigue: Damage to the vestibular
system can result in exhaustion, because you now have to consciously
work at maintaining your balance.
·
Memory problems: Memory problems can
result because areas of your brain that were previously used for thought and memory, must
constantly work on keeping you balanced. As a result, you may grope for words, forget what was just
said, be easily distracted or have trouble concentrating.
·
Muscular aches and pains:
Another
seemingly-unlikely result of vestibular ototoxicity are muscle pains due to failure of the
vestibulo-spinal reflex (the reflex dictating automatic muscle changes in response to
changing movement). If the reflex fails, you have to consciously control it. You may make your
muscles rigid as you strain to keep your balance.
·
Nausea: Nausea is a relatively
common side effect of vestibular damage that results from your
brain's confusion over vestibular sensory inputs.
·
Visual problems: A host of visual problems
can result if the vestibulo-ocular reflex (the reflex that stabilizes your eyes in
space) is damaged. As a result, you may have trouble reading since everything seems
blurry or fuzzy. You may have trouble focusing your eyes—particularly on moving or distant objects.6
·
Vomiting: Vomiting is a common
result of a damaged vestibular system. Often vomiting and vertigo go
together.
·
Vague feelings of unease: Sometimes you can't put your finger on exactly what
is wrong, but
you feel vaguely uneasy. You may feel that things seem wrong or unrea1.7 This too, can be a
result of a damaged vestibular system.
3. Central
Nervous System (CNS) Side Effects
·
Central auditory processing disorder: Sounds may enter our ears and be processed correctly, but these sound signals may
be delayed or scrambled after they
leave our inner ears. This scrambling can occur as the sound signals are processed by the neuronal networks that make up
our auditory nerves, or in various
parts of our brains. When this processed sound reaches the conscious levels in our brains where we "hear,"
we may hear a bunch of gibberish. This is known as a central auditory processing disorder. Several ototoxic
drugs/chemicals have this effect.
4. Outer/Middle Ear Side Effects
·
Ceruminosis: Some drugs cause
excessive ear wax production. This excess wax can block our ear canals
and cause temporary hearing loss.
·
Ear pain: Medically called otalgia,
ear pain is typically the result of middle ear infections. 154 drugs
have ear pain associated with their use.4
·
Otitis externa; 0.
media: Otitis is typically an opportunistic infection of the outer (0. externa) or
middle (0. media) ear. Many of the drugs listed as having otitis as an ototoxic
side effect do not directly cause these conditions. Rather, these infections
come in and take over when an opportunity presents itself—i.e. an ototoxic
antibiotic killing off the "good bacteria" in the ear canal, leaving
it wide open to
an opportunistic invasion of "bad bacteria." 138 drugs are associated
with otitis.4
Risk Factors
Some people take ototoxic drugs with seeming
impunity. Others take one little dose, and wham—there goes their ears. Why?
The short answer is that we are all different. Each
person (patients and professionals) is a unique biological case study! No two are exactly the
same. Therefore, it should be no surprise that we vary in our sensitivity to
ototoxic drugs.
Researchers have identified a number of factors that
increase the risk of our having an ototoxic reaction when taking certain drugs. Here
are 20 of the risk factors (in no particular order of importance).
1.
You are very young—including unborn children.
2.
You are a senior (over 60 years).
3.
You have certain
hereditary (genetic) factors that make you more susceptible than the general population.
This is particularly true if you take Aminoglycoside antibiotics.
4.
You already have a sensorineural hearing loss, balance problems or some
other form of pre-existing ear damage.12
5.
You have had previous ear damage (hearing loss) from exposure to
excessive noise.
6.
You have problems with your kidneys. For some reason, people with kidney problems have an
unusually high incidence of hearing loss, even without drug use.10
7.
You are
extremely sensitive to drugs or have a low tolerance for drugs.
8.
You have had ototoxic reactions to drugs in the past. Not only does the
risk increase, but
the resulting ototoxic damage has a tendency to be more severe and is more
likely to be permanent.7
9.
You have previously used ototoxic drugs, or you have taken repeated
courses of the same ototoxic drug.
10. You have taken certain
drugs for a long time—especially if you have taken a drug for longer than the
manufacturer recommended.
11. You can be at higher
risk if an ototoxic drug is not administered properly—i.e. larger than recommended
dose, higher that recommended cumulative dose, faster dose than recommended
(injection or intravenous).7
12. You have been given an
inappropriate dose—i.e. a child given an adult dose, or an overweight person
given a dose based on total weight rather than on lean body weight (especially true
if taking an Aminoglycoside antibiotic).7
13. You are dehydrated.
14.
You have taken ototoxic Diuretics at the same time as other ototoxic
drugs or if you have used or are using two or more ototoxic and/or nephrotoxic (toxic
to the kidneys) drugs at the same time.
15. You have had previous ear
infections.
16. You are generally in poor
health.
17. You have abnormal
laboratory values such as reductions in serum albumin, serum red blood cells,
hematocrit, hemoglobin or you have rising serum creatinine levels.7
18. 18. You have
had radiation treatments on your head or ear.6
19. 19. You have
bacteremia (bacteria in the bloodstream).7
20. 20. You have either eye or
proprioceptive (balance) problems. This increases the chances that you will
have a more serious result on your life-style if vestibular ototoxicity does
occur.7
Reduce The Risk—Here's How
You cannot do anything about certain ototoxic risk
factors such as your age or your genetic makeup. However, there are still some
things you (and your doctor) can do to lessen your risk of having an ototoxic reaction from
taking certain drugs.
Here are some things you and your doctor can do.
1. Be aware of the early warning signs of
ototoxicity. The are (in order of frequency):
you feel dizzy; your ears begin ringing (tinnitus); your existing tinnitus gets worse or you hear a new kind of
tinnitus sound; you feel pressure in your
ears (unless you have a head cold); your hearing gets worse or begins
fluctuating; or you develop vertigo (spinning sensation).
2. Tell your doctor you are
hard of hearing, especially if you have a sensorineural hearing loss and/or
suffer from balance problems. Also, let him know if you have tinnitus.
3. Always discuss possible
side effects with your doctor before you begin a new medication.
4. Follow your doctor's
dosage instructions exactly. At the same time, make sure your doctor does not
exceed the drug manufacturer's dosage instructions when he prescribes drugs for you.
5. Use the same pharmacy for
all your prescriptions so they will know all the drugs you are taking. That way
they can advise you of any known dangerous drug combinations.
6. Always read the labels on
over-the-counter medications and particularly watch for ototoxic side effects.
7. Drink plenty of fluids so
you don't get dehydrated. This is especially important if you have a
fever or are
taking loop diuretics.
8. If you have kidney
problems, have your health care professionals carefully monitor your kidney
function and report abnormalities immediately. Your doctor needs to know how
well your kidneys are working before he prescribes various medications.9. Avoid taking multiple ototoxic drugs at the same time.
10. Avoid noisy environments
for at least 6 months after you have completed a course of an Aminoglycoside
antibiotic or platinum compound such as Cisplatin.8
11. If you are beginning treatment with an ototoxic
drug such as any of the Aminoglycoside
antibiotics, Loop diuretics or platinum compounds such as Cisplatin,
it is important that you have a
baseline high-frequency audiogram done before
you begin treatment and then serial high-frequency audiograms (testing those frequencies above 8,000 Hz) during and after
drug therapy.
12. If you have had
vestibular (balance) problems from taking any drugs, be very careful not to damage
your vestibular system further by taking drugs known to damage your vestibular
system.
When you are aware of the many drugs that can
damage your ears and the many risk factors that can make you even more susceptible to
ototoxic side effects than the general population, you can take steps to protect your
precious ears.
You will then be in the
position to take control and make informed decisions about your health care. For
example, "Joan" takes Celecoxib
for her arthritis. When she takes it, her tinnitus gets louder, but her
arthritis problems improve. She chooses the tinnitus over the arthritis pain. That is
her choice and she is content to live with it.
"Harold," on the other hand, began taking Amitriptyline and soon noticed he had
severe tinnitus. He didn't like this one bit and wrote to me for help. I
suggested the Amitriptyline may be causing his
tinnitus. With his doctor's permission, he stopped taking the drug. Twelve
days later, he joyfully reported that his tinnitus went away. That was his
choice. He is happy he made it.
When it comes to the health of your ears, you, too, have a choice. Use it
wisely.
Notes
1 In this paper, drug classes are in small capitals
(ACE INHIBITORS), generic drug names are in bold (Enalapril) and brand names are in italics (Vasotec).
2 The brand names listed here are neither more or
less ototoxic than any brands of this same generic drug that are not listed. I have
simply chosen, more or less at random, one brand as a representative of all the brands
available for that generic drug.
References
3 Bauman, Neil. 2002. When
Your Ears Ring. Cope With Your Tinnitus. Here's How. Center for Hearing Loss Help. 49 Piston Court,
Stewartstown, PA 17363.
4 Bauman, Neil. 2003. Ototoxic Drugs Exposed, Second Edition. Center for
Hearing Loss Help. 49 Piston Court, Stewartstown, PA 17363.
5 Guidelines for the
audiologic management of individuals receiving cochleotoxic drug therapy. 1994. American
Speech-Language-Hearing Association. 36(3), Supplement No. 12.
7 Haybach,
Patty J. 1999. Balance and hearing: At
risk from drugs . Course #170.
8 Kalkanis,
James. 2001. Inner ear-Ototoxicity. eMedicine
. 2(7).
9 Shlafer, Marshal. 2000. Ototoxic drugs . University of Michigan Medical School.
1° Staab, Dr. Wayne J. 1991. The
Rexton guide to better hearing . 512 East Canterbury Lane, Phoenix, Arizona
85022.
11 Stedman's Medical Dictionary . 2000. 27th Edition. Lippincott Williams &
Wilkins. Baltimore, Maryland.
Part Two: Ototoxicity and the Practice of Audiology
Part One of this series presented an overview of
the hundreds of ototoxic drugs currently available and how their potential side effects
relating to hearing and balance turn countless lives upside down. Part One also detailed
risk factors that predispose people to ototoxic effects and concluded with what individuals
can do to reduce their risk.
In Part Two, we'll examine things you, as an
audiologist, can do to help your patients when their ears "butt heads" with ototoxic
substances.
Think
"Drugs" When Assessing Hearing Loss
As you know, when
patients present for hearing evaluations, it is important to ask what medications they're
taking. However, the importance of this questioning is not limited to a thorough and complete
history. Rather, this knowledge may indeed impact their current status and future-based
medical decision making.
If you look up their medications in Ototoxic Drugs Exposed,1 you'll quickly get an idea as to what may be
happening to their ears. If ototoxic side effects started (or increased) around the time they
began taking certain drugs, the ototoxic "index of suspicion" is elevated, and indeed,
their current medications may be damaging their ears.
Given an elevated index
of suspicion, and armed with objective data, you might contact the physician and suggest
that perhaps alternative, non-ototoxic alternative medications might be an option.
For example, suppose a patient comes to you with
severe hyperacusis which is disrupting her life. What do you do? Do you immediately think
of something like Hyperacusis Retraining Therapy, or do you think
"drugs?"
I suggest as a first step—think "drugs."
When patients ask me what they can do about their
hyperacusis, among the first questions I ask is, "What happened in your life just
before the hyperacusis began? Did you start taking new medications or was there a change in the
dose of existing medications?" I ask for a complete list of their
medications and I look them up in Ototoxic
Drugs Exposed to see if any of them are known to cause hyperacusis. If any of them are
known to cause hyperacusis, I suggest to the patient that he/she contact the doctor to
investigate alternative drugs with the same benefits, but without hyperacusis as a
known side effect. In certain situations, I may communicate directly with the physician on
these issues.
A psychiatrist explained that a patient of hers had
several psychiatric problems, but the one thing bothering the patient above all else was
severe hyperacusis. The patient had tried hyperacusis remedies without improvement. The
psychiatrist asked me if there was anything that might help her patient.
My first reaction was to "think drugs." I
asked what medications the patient was on and
what medications she had
been on at the time the hyperacusis began. When I received the list of
medications, I discovered that this patient was taking not just one, but three
drugs known to cause hyperacusis! Of all the thousands of drugs on the market,
only 38 are known to cause hyperacusis, yet this poor patient was taking three
of them at the same time!
I suggested the psychiatrist consider taking the
patient off those three particular medications (if medically possible) and then see
whether the patient's hyperacusis was reduced or eliminated.
A man contacted me telling me had severe tinnitus
and he wanted to know if there was anything he could do about it. Instead of
suggesting a tinnitus masker or Tinnitus Retraining Therapy (TRT) or other treatments, I
immediately thought "drugs." I asked if he had started any new
medications about the time his tinnitus began.
He told me his doctor had recently put him on Amitriptyline. I suggested he ask his doctor to change his
medication, if possible, as Amitriptyline
is known to cause tinnitus. A couple of weeks later, he wrote me again, saying
that 12 days after he stopped taking the Amitriptyline,
his tinnitus went away. Again, the solution was simple and effective. Think "drugs."
A woman contacted me as she was experiencing
annoying tinnitus and increasing hearing loss. As is my custom, I thought "drugs."
I discovered she had been self-medicatingtaking large doses of aspirin each
day for the nearly-constant headaches she often suffered.
I suggested to her that her hearing problems and her
tinnitus were very likely a direct result of taking all that aspirin. She stopped taking aspirin.
Six days later she wrote, "I have noticed that I am hearing better now. I have
the TV volume set at level 18 instead of the usual 24. The ringing in my ears is still there
but it is not as bad." Three days later she added, "Today when
someone was talking behind me, I heard every word he said. My hearing still isn't
perfect, but it is better than it was."
The people in the above examples didn't need
expensive or extensive therapy or hearing aids. What they really needed was someone to help
them see that they were damaging their ears due to medications they were taking. In
many cases, you'll be able to help your patients more when you first think
"drugs."
While You Are Thinking
"Drugs," Think "Chemicals" Too
It is not only ototoxic drugs that damage our ears,
there are at least 148 ototoxic chemicals that also give us griefl
Two of the more ototoxic classes of chemicals are
the organic solvents and the heavy metals.
There are a number of
organic solvents. Some of them are benzene,
benzyl alcohol, butyl alcohol, carbon
disulfide, carbon tetrachloride, heptane, hexane, styrene, toluene, trichloroethylene and xylene. Ototoxic
heavy metals include arsenic, cobalt, lead, manganese, mercury and trimethyltin.
Most people likely have a number of ototoxic
chemicals in or around their homes. Some of these ototoxic chemicals include
adhesives, auto emissions, fungicides, glues, grease and spot removers,
insecticides, insulation, lacquers, liquid correction fluid, organic solvents, paint, paint
thinners, resins, room deodorizers, rug cleaners, spray paint, varnishes and wood
preservatives to name a few.13, 14
In addition, people may be exposed to ototoxic
chemicals if they work in one of the many manufacturing plants and factories that use organic
solvents or heavy metals. Such processes as electroplating, shoe manufacturing, dry cleaning, cold
vulcanization, electronic battery manufacture and polyvinyl chloride manufacturing all
use various ototoxic chemicals.14
Further, the pollutants in the air can also hurt
peoples' ears. Depending on the type and severity of the air pollution, people can end up
with hearing loss, balance problems or other damage to their ears.2
Most people probably think of air pollution as occurring
outside. However, dangerous air pollution also resides within homes, offices and
factories. Many of the indoor pollutants are organic solvents. When people inhale fumes from
these solvents, they slowly but surely damage their ears.
One study of workers in a rubber factory revealed
47% had subclinical abnormalities in the auditory pathways and in their brainstems, due
to solvents used in manufacturing rubber.16 One patient lost her hearing resulting from several
years of using spray varnish in her garage without adequate ventilation. Toluene in the varnish was the culprit.
Sometimes, ototoxic damage from organic solvents is
obvious—such as when it results in massive hearing loss or roaring tinnitus. However,
in other cases (see above study) results can be insidious and subtle, presenting as impaired
central auditory processing. Even though the chemical hasn't caused reduced
"hearing" as might be expected on an audiogram, the person
affected can't understand everything they hear.
A bit of probing may reveal that hearing loss is the
result of exposure to an ototoxic chemical where you least expect to find it.
Therefore, in addition to thinking "drugs," also think
"chemicals."
Drug Interactions and
Ears
Little is known about
how ototoxic drugs adversely affect our ears. Dramatically less is known about
ototoxic side effects when two or more ototoxic drugs are consumed at the same
time. However, some interesting (and important) things have come to light in
recent years.
When a person takes two or more ototoxic drugs at
the same time, or one immediately following the other, there are two likely
outcomes. The ototoxic effects of each drug can either be additive, or
the ototoxic effects can be synergistic.
In the first case, the total effect on the ears
will be the sum of the effects of each drug as if they were taken
separately. For example, if one ototoxic drug causes 2 "units" of damage and the second
drug causes 3 "units" of damage, the resulting damage on the ear would be 5
"units" (2 + 3 = 5). This is the additive effect.
However, with some drug combinations, using the
same example above, the result is not 5 "units" of damage as you might expect,
but a larger number—say 10 "units" of damage. This represents a synergistic
effect. With synergistic effects, the resulting damage is always greater than the
sum of the damage of each individual drug.
To protect ears as much as possible, people should
not take multiple ototoxic drugs at the same time, especially if they are known to have
synergistic ototoxic effects.
Researchers have discovered that the order a person
takes certain ototoxic drugs can make an enormous difference as to whether they have
much of a resulting hearing loss or not. With some drug combinations, if you take the
drugs sequentially, and not simultaneously, you can avoid the synergistic
effect.
For example, in one medical treatment, doctors put
their patients on two drugs, a Loop diuretic (e.g., Furosemide) and an Aminoglycoside antibiotic (e.g., Tobramycin). If the patient completes
the course of the Loop diuretic before he
begins the Aminoglycoside antibiotic, the resulting hearing loss from these two drugs is additive.
However, if the patient takes both drugs simultaneously or if the Aminoglycoside
antibiotic is administered first, followed by the Loop diuretic—the two drugs act
synergistically to significantly damage the patient's ears.25
Not only do certain ototoxic drugs react
synergistically with each other, but they have another nefarious characteristic.
Their ototoxic side effects can react synergistically with noise.
Certain ototoxic drugs
when taken "normally" can result in a certain degree of hearing loss. However, if they
are being taken while the patient is exposed to loud noise, the noise combines
synergistically with the ototoxic side effects of the drug to cause even greater hearing loss than
might otherwise be expected.
Some of the drugs that have this vicious effect
include aspirin,20 the anti-cancer drug Cisplatin,22 the microbial antibiotic Chloramphenicol3 and Aminoglycoside antibiotics such as Gentamicin12 and Kanamycin.23
This same synergistic effect on hearing loss between
the ototoxic side effects of certain
drugs and noise also
occurs between certain chemicals and noise. Chemicals that make our ears more prone to
hearing loss as a result of noise include organic solvents such as carbon disulfide, dinitrobenzene, styrene, trichloroethylene, toluene and xylene as well as the asphyxiant carbon
monoxide and the heavy metal lead.4' 10, 17, 26
Other chemicals with this same nefarious
characteristic include arsenic, butyl
alcohol, butyl nitrite, heptane,
hexane, manganese, mercury and trimethyltin.19 This apparently is just the tip of the iceberg. Suspicion is already cast on carbon tetrachloride,
various other
metals and asphyxiants.17'2°
Just how pronounced is this synergistic effect?
Sometimes the results can be dramatic! In a study of Brazilian workers, those exposed to both noise and toluene had a 53% incidence of hearing loss. In contrast, those
exposed to noise alone had a 26% incidence rate while the control group had an incidence rate of only 8%. When
these results were adjusted for age,
they showed that noise exposure increases the risk of hearing loss by 4.6 times. When the noise was combined with exposure
to toluene, the risk jumped a whopping 27.5 times!21
In another study, workers were grouped into one of
four groups—those exposed to both noise and toluene,
those exposed to toluene alone,
those exposed to noise alone, and those not exposed to either toluene or noise (the control group). The hearing loss of those exposed to noise alone
was 4 times greater than the control group; the hearing loss of those exposed to toluene alone was 5 times greater; and
the hearing loss of those exposed to both noise and toluene was 11 times greater! 17
One treacherous result of certain ototoxic drugs
combined with noise is something you'd probably never suspect—the length of time a
person's ears are still susceptible to the synergistic effects of ototoxic drugs and
noise—after the drug has been discontinued.
If you tell a person not
to take certain drugs while he is exposed to noise, he might think you are referring to the
days he is actually taking the drug therapy. Surprise! Not true! A person has to avoid
noise for much, much longer.
When a person takes Aminoglycoside antibiotics or
platinum anti-cancer drugs, such as Cisplatin, they are quickly
transported to his inner ears. The problem is that, once there, these drugs persist in
the inner-ear fluids long after they have disappeared from the bloodstream,11 not just for a few days, but for several weeks to
several months,15 and up to a year later!
During the time these
drugs are present in peoples' inner ear fluids, they can be damaging their ears. More
importantly, during this time, their ears are especially susceptible to the synergistic effects of
loud noise.15 This means that if
people have taken Aminoglycoside antibiotics or Cisplatin
and are now finished with this drug therapy, their ears are still in danger of even more
hearing loss if they expose them to loud noise any time in the next few months or more,
depending on their specific body chemistry.
This has important
implications for the audiologist treating hearing aid patients with hearing aids and other
amplification systems. Dr. James Kalkanis, M.D., recommends setting the gain and
maximum power output (MPO) as low as possible in order to protect your patients' ears
while their ears are very sensitive to the effects of noise, secondary to ototoxic medications. If
a patient already wears hearing aids, you should instruct him to keep the volume down
during this time also.15 The same is true for people exposed to ototoxic chemicals in the
workplace. Workers exposed to ototoxic chemicals should be advised that it is in
their best health interest to keep the volume down on their hearing aids, and to keep the
work environment as quiet as is possible.
What is a safe level in
such situations? The only thing known for sure is that current standards are not
stringent enough. Researchers were surprised to discover that when noise and ototoxic
agents team up to damage ears, this damage can occur even though exposure to both noise and chemicals are within currently acceptable limits! 10
High Frequency Hearing
Testing is Important
Many ototoxic drugs and chemicals begin destroying
hearing at the highest frequencies first, and as exposure continues, lower
frequencies become involved. Since hearing is traditionally only
tested up to 8 kHz, most initial cases
of hearing loss from ototoxic drugs and chemicals are never revealed
by standard audiometric testing.
However, high-frequency audiometry is important if
hearing loss from ototoxic drugs is to be minimized or prevented. High-frequency
audiometry can reveal the early effects of ototoxic drugs before tinnitus appears or hearing
damage is visible on a conventional audiogram (250 and 8,000 Hz).
In studies involving Cisplatin, the first indications
of hearing loss always appeared between 10,000 and
16,000 Hz.24 Of course, standard audiometric testing would not have revealed this hearing
loss, as it impacts higher than typically tested frequencies.
Several ototoxic chemicals cause initial hearing loss in the high
frequencies. For example, high-frequency hearing testing revealed that workers exposed to
low concentrations
of styrene fumes for 5 years had
hearing losses in the high frequencies even though their hearing tests in the conventional
frequencies were normal. If high-frequency hearing testing hadn't been done, styrene could have been given a clean
bill of health -- even though it is ototoxic.
Inhaling styrene
fumes is known to cause a reduction in the upper limit of hearing. Researchers concluded
that the upper limit of hearing is a sensitive indicator for early detection of ototoxicity
in workers exposed to styrene18 and indeed, probably for many or most ototoxic drugs and chemicals.
One study demonstrated that audiometric testing across the conventional
hearing range is the least effective method to
determine initial hearing loss.5 Therefore, if you want to know whether drugs or
chemicals are insidiously stealing your patients' hearing, you need to test their
hearing up to the highest frequency possible.
Since ototoxic hearing loss typically begins at the
highest frequencies and progresses through lower ones, audiologists should monitor the
highest measurable frequencies in people with pre-existing hearing loss, to
provide the earliest possible warning of further drug-related hearing
loss.
Early detection does not, by itself, prevent
further damage to a person's ears. However, it does give doctors time to
adjust the dose or stop the medication altogether before hearing loss spreads to the
conventional frequencies.6 If monitoring is restricted to frequencies below 8000 Hz, by the
time audiologists detect new/additional hearing loss, hearing loss will have already
affected those frequencies necessary for speech.
How good is high-frequency testing? When
researchers compared testing high frequencies versus testing conventional
frequencies, one study revealed that 52% of hearing losses were first detected in the high-frequency range only. That study
revealed that more than half the people with drug-induced hearing loss have
hearing loss that was not detected by conventional
means. If only high-frequency hearing testing had been done, 67% of all the ears
demonstrating initial hearing loss due to ototoxicity would have been found.7
Another study revealed that only 13.5% of the
people (ears) studied had initial drug-related hearing loss in the conventional
frequencies. An additional 24% had initial detectable hearing loss in the conventional
frequencies as well as the high frequencies. Thus, a whopping 62.5% of
drug-induced hearing loss likely goes undetected because it initially only occurs in the traditionally
not-tested high frequencies! 8 If only the high frequencies had been
tested, 86% of all cases of drug-induced hearing loss would have been detected.
Testing all frequencies between 125 Hz and 20,000
Hz is time consuming and of course, adds additional expense to the evaluation.
Fortunately, researchers have recently discovered a five-frequency slope that is very
sensitive to the ravages of ototoxic drugs. The beauty of this five-frequency slope testing is
that it is highly sensitive to initial ototoxic hearing loss.
This five-frequency range varies depending on each person's
pre-existing hearing loss and thus is unique to each person. These five frequencies are generally
separated by 1/6 octave.
For example, a person with pre-existing hearing
loss might have a five-frequency slope consisting of 8, 9, 10, 11.2 and 12.5 kHz.9 Since each person's
hearing loss is unique, the testing process is tailored for each person and this can be easily and
accurately accomplished.
Using an audiometer calibrated to accurately test up to 20,000 Hz,
determine the highest frequency your patient can hear. (Note: the hearing loss at this
frequency must be 100 dBor less.) Second, test
this frequency and the next four lower consecutive audiometric test frequencies. This becomes
the individual patient's five-frequency slope range.6
Depending on the
patient's particular hearing loss, this five-frequency slope may all lie within the extended
high-frequency range, it may straddle the 8,000 Hz boundary, or it may reside completely
within the conventional frequencies.
Just how effective is this five-frequency slope in
detecting hearing loss from ototoxic drugs? The results may surprise you!
In one study of the ototoxic effects of Cisplatin, if only the five frequencies
in the five-frequency slope had been tested, 93% of the people with ototoxic
drug-induced hearing loss would have been detected.6 This is in sharp contrast to the 39% detected in
this same study using only the conventional frequencies.
Other studies have yielded similar results. For
example, another study reported that if only the five-frequency slope values were tested,
hearing loss due to Aminoglycoside antibiotics would be detected 84% of the time, and
for Cisplatin, the results would
been 94%.9 Another study revealed
that initial hearing loss would have been detected in 89% of the people with
hearing loss if only the five-frequency slope had been tested. Testing only
conventional frequencies caught just 37%.8
Based on results such as these, the routine use of
high-frequency audiometry is not just "nice," it is essential.15
For hospital in-patients who must undergo drug
therapy with ototoxic drugs, having complete audiometric testing can be a problem,
especially if they are unconscious, semiconscious or very sick. In such cases, using a
conventional audiometer and test protocols is difficult, if not impossible. In these
situations, auditory brainstem response (ABR) techniques modified to
work in the higher frequencies can be effective tools. In one such study, high-frequency
tone-burst-evoked ABRs identified 93% of the initial changes in hearing loss.7
The five-frequency slope protocol is fast and
efficient and has been proven effective in providing early warning of hearing loss.
I recommend
that the five-frequency slope protocol become the accepted standard practice in audiometric testing to help patients
save precious hearing that otherwise might be lost to the ravages of ototoxic
drugs.
References
1
Bauman, Neil. 2003. Ototoxic Drugs Exposed, Second
Edition. Center for Hearing Loss
Help. 49 Piston Court, Stewartstown, PA 17363.
2 Bisesi, Michael, and Allan Rubin. 1994. Chemical
air pollutants and otorhinolaryngeal toxicity. Journal
of Environmental Health. 56(7):24.
3 Carmen, Richard. 1999. Chemicals &
hearing-Danger ahead. Hearing Health
Magazine (March/April).
4
Cary, R., S. Clarke, and J. Delic. 1997. Effects of
combined exposure to noise and toxic substances-Critical review of the literature. Ann. Occup. Hyg. 41(4):455-465.
5 Fausti, S. A., et al. 1992. High-frequency
audiometric monitoring for early detection of aminoglycoside
ototoxicity. Journal of Infectious
Diseases. 165(6):1026-32.
6 •
Faust, S. A., et al.
1993. High-frequency monitoring for early detection of cisplatin ototoxicity. Arch Otolaryngol Head Neck Surg. 119
(6):661-6.
7 Fausti, S. A., et al. 1993. High-frequency testing
techniques and instrumentation for early detection of ototoxicity. I Rehabil. Res. Dev. 30(3):333-41.
8 Fausti, S. A., et al. 1994. High-frequency
audiometric monitoring strategies for early detection of ototoxicity. Ear Hear. 15(3):232-9.
9 Fausti, S. A., et al. 1999. An individualized
sensitive frequency range for early detection of ototoxicity. Ear Hear. 20(6):497-505.
1° Forge, Andrew. 1999. Industrial chemicals are hazardous to hearing. Lancet. 353(9160):1250.
11 Guidelines
for the audiologic management of individuals receiving cochleotoxic drug therapy. 1994. American Speech-Language-Hearing Association. 36(3), Supplement No.
12.
12 •, Timothy. 2001. Gentamicin toxicity.
13Haybach, Patty J. 2003. Recognizing Ototoxicity..
14
Haybach, Patty
J. 1999. Balance and hearing: At risk
from drugs. Course #170.
15 Kalkanis, James. 2001. Inner ear-Ototoxicity. eMedicine. 2(7).
16 Kumar, V. and 0. Tandon. 1997. Neurotoxic effects of rubber factory
environment. An auditory evoked potential study. Department of Physiology, University of
Medical Sciences, Delhi, India. Electromyogr.
Gin. Neurophysiol. 37(8):469-73.
17 Morata, Thais C., and Derek E. Dunn. 1994. Occupational exposure to
noise and ototoxic organic solvents. Archives
of Environmental Health. 49(5):359.
18 Morioka, Ikuharu and Mototsugu Kuroda. 1999. Evaluation of organic
solvent ototoxicity by the upper limit of hearing. Archives of Environmental Health. 54(5):341.
19 Niall, Paul. 1998. The effects of
industrial ototoxic agents and noise on hearing. University College,
London, England.
20 Rosen, Elizabeth. 2001. Noise Inducted Hearing
Loss. Grand Rounds Presentation, UTMB, Dept. of Otolaryngology. January 10, 2001.
21 Rybak, Leonard. 1992. Hearing: The effects of chemicals. Otolaryngology-Head and Neck Surgery. 106(6):677-686.
22 Soh, K. 1999. Noise is a public health and social problem in Singapore. Singapore Med. J. 40(9).
23 Suter, Alice. 1991. Noise and its effects. Administrative Conference of
the United States. November.
24 Tange, R. A., W. A. Dreschler, and R. J. van der Hulst. 1985. The
Importance of high-tone audiometry in monitoring for ototoxicity. Arch. Otorhinolaryngol. 242(1).
25 Troost, B. Todd, and
Melissa A. Walker. 1998. Drug induced vestibulocochlear toxicity. In: Iatrogenic Neurology. Butterworth-Heinman. Boston.
26 WorkPro. 1999. Southeastern Ohio Regional Medical Center.
No comments:
Post a Comment