K-14 Drug-Induced Hearing Impairment

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    DRUG-INDUCED

    SPECIAL SENSE IMPAIRMENTS

    Dr.Datten Bangun MSc.SpFKDr.Yunita Sari Pane,M.Si

    Dept Farmakologi & Therapeutik

    Fakultas Kedokteran USU

    M E D A N

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    I.Ototoxicity;

    Stedman s Medical Dictionary: ototoxicity is property of being

    injuries to the ear ----- any side-effect of a drug that damage theears,either the outer,middle or inner ear

    is ototoxic

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    Drug-induced hearing loss,

    ototoxicity

    Mechanism unclear, possibily related

    to drug type, dosage, route, geneticpredisposition, etc

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    Ototoxic drug (more than 90)

    Aminoglycoside antibiotics

    Antitumor drug- cisplatin, carboplatin

    Diuretic- furosemide, ethacrynic acid Salicylate-aspirin

    antimalarial drug- quinin

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    Clinical characteristics of ototoxic

    deafness

    Bilateral hearing loss

    Hearing loss happens at highfrequency

    Reversible or progressive

    With tinitus, vertigo

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    How common are ototoxic side-

    effect?= no one really knows

    Ex.

    Cisplatin ( a cytostatic):

    - almost anyone who takes the drug

    ends up with hearing loss---

    almost100 %

    - usually irreversible

    Aminoglycosides ( an antibiotic)

    - in a study--- 25-30 %- other study --- 63 %

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    Ototoxic Side-effects

    Ototoxic side-effects can damage the

    ears in many different ways:

    1.Cochlear side-effect:

    = tinnitus (ringing in the ears-- 447 drugs

    = hearing loss --- 230 drugs

    - can range from mild---- profound

    - may be temporary or permanent

    Note: ototoxic drugs generally first destroyhearing in the very high frequencies,

    (above 8000 Hz,not normally tested),

    --- patients are not aware.

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    = distorted hearing;

    - patients do not understand some (or

    much) of what they hear

    = hyperacusis;

    - normal sounds are perceived as beingtoo loud---- 38 drugs

    = feeling fullness in the ears= auditory hallucinations----- 165 drugs

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    2.Vestibular Side-effects

    = dizziness ---- 588 drugs

    = vertigo --- 432 drugs

    = ataxia

    = nystagmus= labyrinthus

    = loss of balance

    = oscillopsia= emotional problems

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    3. CNS effects

    4. Outer/ middle Ear Side-effects- ceruminous

    - ear pain

    - otitis------ :media

    :externa

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    RISK FACTORS:

    1. Age; -very young/even unborn

    - over 60 yrs

    2. Genetic factors--- esp. aminoglycoside

    3. Already has hearing problems

    4. Previous ear damage

    5. Problem with kidney or liver---excretion

    of drugs are delayed6. Already had ototoxic reaction before

    7. Too much drug,either in amount or doses

    8. Dehydration

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    Aminoglycoside ototoxicity

    = Frequency:- 15-50 % of all cases

    = Bilateral vestibulopathy--- oscillopsia= mostly for high frequency (> 8000 Hz----

    tidak dikenali segera oleh pasien )

    Mechanism of action:

    Appear to involve:

    = apoptotic (programmed cell death)

    = formation of free radicals= reduction of mitochondrial protein synthesis

    ---- ATP production

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    Aminoglycosides ototoxicities:

    - gentamicin

    - tobramycin

    - amikacin

    - streptomycin

    ---- 6-13 %

    - netilmycin---- 2,4 %

    Symptoms of ototoxic can be delayed-- 6 weeksafter completion of AG therapy; however 50%

    will recover 1 week to 6 months after discontinu-

    ation

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    Streptomycin

    tends to cause more damage to the vestibularportion than to the auditory portion of the inner ear.

    Although vertigo and difficulty maintaining balance

    tend to be temporary, severe loss of vestibular

    sensitivity may persist, sometimes permanently. Loss of vestibular sensitivity causes difficulty

    walking, especially in the dark, and oscillopsia (a

    sensation of bouncing of the environment with each

    step). About 4 to 15% of patients who receive 1 g/day for >

    1 wk develop measurable hearing loss, which

    usually occurs after a short latent period (7 to 10

    days) and slowly worsens if treatment is continued.

    Complete, permanent deafness may follow.

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    Neomycin

    has the greatest cochleotoxic effect of all

    antibiotics.

    When large doses are given orally or by colonic

    irrigation for intestinal sterilization, enough maybe absorbed to affect hearing, particularly if

    mucosal lesions are present.

    Neomycin should not be used for wound

    irrigation or for intrapleural or intraperitoneal

    irrigation, because massive amounts of the drug

    may be retained and absorbed, causing

    deafness.

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    Kanamycin

    Kanamycin and amikacin are close to

    neomycin in cochleotoxic potential and are

    both capable of causing profound,

    permanent hearing loss while sparingbalance.

    Viomycin has both cochlear and vestibular

    toxicity.

    Gentamicin and tobramycin

    have vestibular and cochlear toxicity,

    causing impairment in balance and hearing

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    CISPLATIN OTOTOXICITY

    = a platinum based chemotherapeutic drug

    Mechanism of ototoxic.-not clearly understood, -- probably:

    =The Reactive Oxygen Species (ROS)

    play a role because cisplatin induce adecrease in plasma antioxidant level

    and suppres the formation of endoge-

    nous antioxidant

    =Cisplatin results in depletion of glutathione

    and antioxidant enzymes in cochlear tissue

    ---- malondialdehyde level increased

    Ot t t

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    Otoprotectors:

    Several drugs have been tried as protection to

    ototoxic effect of cisplatin.

    1. N-acetylcystein ( NAC)

    2. Methionine (MET)

    -aminoacid

    -antioxidant-precursor of gluthatione

    3.Vitamin E

    4.Ebselen; antiinflammatory antioxidant compound,

    acts as a gluthatione peroxidase mimic

    5.Sodium Thiosulfat: when given 4hours after carboplatin

    ----- ototoxicity reduced from 84 to 29 %

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    However:

    I. These otoprotectors shown to reduce

    the antineoplastic effect of cisplatin.

    II .Toxic at high doses

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    QUININE OTOTOXICITY

    Effects: - tinnitus

    - sensorineural hearing loss (SNHL)

    - vertigo

    Mechanism of ototoxicity:- quinine decreased force

    generation in cochlear outer hair

    cells in the lateral cisternae-Cells are elongated and diameter

    dilated

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    Salicylate Ototoxicity

    = first reported by Muller in 1877

    Ex. ASPIRIN

    Symptoms:

    - tinnitus tends to precede the

    deafness

    - bilateral

    - mostly occurred at serum levels of

    35 mg/dl

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    Other theory:

    = a change in the cochlear blood supply as aresult of salicylate-induced imbalance of

    vaso-dilatory prostaglandin and

    vasoconstricting leukotriene

    = change in the cochlear permeability of theouter hair cells

    Mechanism action: probably by:

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    Loop diuretic ototoxicity

    Mahler and Schreiner (1965):

    = reversible SNHL and vertigo after i.v adm. ofloop diuretic ,i.e ethacrynic acid and

    furosemide

    - high dose

    - low dose but rapidly- existing hearing deficits

    - severe hypoalbuminemia

    - heart or liver failure

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    Mechanism of action

    = damage the stria vascularis

    = damage the outer hair cells of cochlea

    by inhibiting Na-KATP-Ase and

    Adenyl cyclase in the stria

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    Prevention of Ototoxicity

    1. Ototoxic antibiotic or drugs should be

    avoided in pregnant women

    2. The elderly and people with pre-existing

    hearing loss should not be given ototoxicdrugs.

    3. The lowest effective dosage of the drug

    should be given and monitored closely.4. If possible,before giving ototoxic drugs,

    hearing should be measured and then

    monitored during treatment

    a e

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    Some Drugs that Cause Ototoxicity

    Type Examples

    Antibiotics Aminoglycosides

    Vancomycin

    Chemotherapeutic

    drugs

    Platinum-containing drugs (eg, cisplatin )

    Diuretics Ethacrynic acid

    Furosemide

    Other Quinine

    Salicylates

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    Drug-induced smell disorders

    Usually ,smell disorders----- taste

    disorders.

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    Can You Smell That?

    Anatomy and Physiology of Smell

    Baca anatomi & fisiologi

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    Many depend upon smell for livelihood or safety:

    Cooks

    Homemakers

    Firefighters

    Plumbers

    Wine merchants

    Perfumers

    Cosmetic retailers

    Chemical Plant Workers

    I sense a hint ofYasmine and roses

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    The Sense of Smell

    Often downplayed

    Vital to our everyday existence

    Stop and smell the roses

    Has the milk expired?

    Essential in our ability to taste

    Occasionally the first sign of

    other disorders

    Rarely tested

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    Definitions

    Total Anosmia: inability to smell all odorants on

    both sides of the nose

    Partial Anosmia: inability to smell certain

    odorants Specific Anosmia: lack of ability to smell one or

    a few odorants

    Hyperosmia: abnormally acute smell functionand often interpreted as hypersensitivity to odors

    Dysosmia: distorted or perverted smell

    perception

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    Definitions

    Parosmia/Cacosmia: change in quality of an

    olfactory cue

    Phantosmia: odor sensations in absence of an

    olfactory stimulus Olfactory agnosia: inability to recognize odor

    sensations despite olfactory processing,

    language, and intellectual function intact

    Seen in certain stroke and postencephalitic

    patients

    Presbyosmia: smell loss due to aging

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    Olfactory connections to the Brain

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    Disorders of Olfaction

    Obstructive Nasal and Sinus Disease

    Upper Respiratory Infection

    Head Trauma

    Aging

    Congenital Dysfunction

    Toxic Exposure

    Neoplasms

    HIV

    Epilepsy and Psychiatric Disorders

    Medications

    Surgery

    Idiopathic Loss

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    Medications

    Amebicides and antihelmintics: Metronidazole;niridazole

    Local Anesthetics: Benzocaine; Procaine; Cocaine;

    Tetracaine

    Anticholesteremics: Clofibrate

    Anticoagulants: Phenindione

    Antihistamines: Chlorpheniramine

    Antiproliferatives: Doxorubicin; Methotrexate;

    Azathioprine; Carmustine; Vincristine Antirheumatic, analgesic-antipyretic, anti-

    inflammatory: Allopurinol; Colchichine; Gold;

    Levamisole; D-pencillamine; Phenylbutazone; 5-

    thiopyridoxine

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    Medications (continued)

    Antiseptics: Hexetidine

    Antithyroid agents: Carbimazole; Methimazole;

    Methylthiouracil; Propylthiouracil; Thiouracil

    Agents for dental hygeine: Sodium lauryl sulfate

    (toothpaste)

    Diuretics and antihypertensive agents: Captopril;

    Diazoxide; Ethacrynic acid

    Hypoglycemic agents: Glipizide; Phenformin

    Muscle relaxants and Parkinson treatment drugs:

    Baclofen; Chlormezanon; Levodopa

    Opiates: Codeine; Hydromorphone; Morphine

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    Medications (continued)

    Psychopharmacologics: Carbamazepine;

    Lithium; Phenytoin; Psilocybin;

    Trifluoperazine

    Sympathomimetic drugs: Amphetamines;

    Phenmetrazine; Fenbutrazate

    Vasodilators: Oxyfedrine; Bamifylline

    Others: Germine monoacetate;

    Idoxuridine; Iron sorbitex; Vitamin D

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    Treatment and Management

    Conductive Loss vs Receptive Loss

    Conductive loss of smell: major olfactory

    dysfunction responsive to treatment of

    nasal disease

    Opening air passageways:

    Intranasal steroids

    Antibiotics

    Allergy therapy

    Ethmoid Sinusitis

    Intranasal tumors

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    Receptive Loss Treatment

    Vitamin A:

    Necessary in repair of epithelium

    White rats become anosmic on Vitamin A

    deficient diet

    Mammalian olfactory epithelium with

    considerable amounts of Vitamin A

    Duncan and Briggs studied Vitamin Asupplementation and found successful

    restoration of at least partial olfactory ability in

    50 of 56 pts

    Other authors unable to reproduce benefit

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    Receptive Loss Treatment

    Zinc

    Zinc-deficient adult mice probable anosmia

    Severe deficiency rare and difficult to

    substantiate

    Occasional reports of improvement in

    anosmia with zinc therapy

    Aminophylline cAMP role in transduction

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    Managing Olfactory Loss

    Ifno known causes found: reassurance Discuss improving seasoning of diet for

    remaining sensory modalities

    Emphasize taste, color, texture, viscosityand feel of foods

    Smoke and fire detectors are mandatory

    Patients should elicit confidential help for

    matters of odor

    Switch to electric appliances and non-

    explosive heating or cooling fuel from

    natural gas

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    Conclusions

    Hearing is one of the most primitive of our

    senses

    Strong correlation with many of our other

    senses, our memories, and quality of life ingeneral

    Often not addressed enough with patients

    Anosmia may be a marker for certain

    conditions and diseases

    Many different conditions can lead to

    anosmia

    Treatment options are often limited

    Terima kasih untuk perhatian

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    Terima kasih untuk perhatian