02/04/2015

PENGGUNAAN OBAT PADA

GANGGUAN TELINGA
Department Of Pharmacology

External ear

02/04/2015

Hearing

Conductive

Sensorineural

Ototoxic Drugs
Certain drugs can cause SN HL.
Toxicity effects vary from mild and
temporary to severe and permanent.
Mild and Temporary
Aspirin (especially in large doses) can cause
hearing loss (and/or tinnitus), but not in most
people,

Severe and Permanent

An especially important group of antibiotics
(aminoglycoside)

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ANTIBIOTICS WITH GOOD EVIDENCE FOR OTOTOXICITY

Drug

Vestibulotoxi
city

Hearing
Toxicity
yes

High IV doses only

Gentamicin

8.6%

minor

Usually 2 weeks

Streptomycin

very toxic

minor

Erythromycin

dihydrostreptomicin minor toxic

very toxic

Tobramycin

minor in 6%

Yes

Netilmicin

Less toxic than Gentamicin

2.4%

Amikacin

not toxic

13.9%

Neomycin

minor

very toxic

Kanamycin

minor

very toxic

Etiomycin

moderate

Vancomycin

nontoxic

none to
moderate

Metronidizole

toxic (rarely)

unknown

Capreomycin

Toxic Level

In topical ear drops

synergistic with gentamicin

yes
Table from: http://www.tchain.com/otoneurology/disorders/bilat/ototoxins.html.

OTHERS
Salicylates
1. aspirin and aspirin-containing products
2. salicylates & methyl-salicylates
Non-Steroidal Anti-Inflammatory Drugs
1. diclofenac
2. etocolac
3. fenprofen
4. ibuprofen
5. indomethacin
6. naproxen
7. piroxicam
8. sulindac

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OTHERS
Diuretics
1. bendroflumethazide
2. bumetadine
3. chlor-thalidone
4. ethacrynic acid
5. furosemide
Erythromycin
Vancomycin (Similar to aminoglycosides
Minocycline (Similar to erythromycin).
Polymixin B & amphotericin B (Antifungal preparations).
Capreomycin (Anti-tuberculosis medication).

OTHERS
Chemotherapeutic Agents
1. bleomycine
2. bromocriptine
3. carboplatinum
4. cisplatin
5. methotrexate
6. nitrogen mustard
7. vinblastin
8. vincristine
The ototoxic effects can be minimized by
carefully monitoring blood levels).

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OTHERS
Quinine
1. chloroquine phosphate
2. quinacrine hydrochloride
3. quinine sulfate
The ototoxic effects are very similar to those
of aspirin.
Mucosal Protectant
misoprostol

NOTES
Of particular interest is that topical ear drop
medications containing gentamycin or
neomycin do not appear to be ototoxic in
humans unless the tympanic membrane (ear
drum) is perforated.
When a solution of an aminoglycoside
antibiotic is used on the skin together with an
aminoglycoside antibiotic used intravenously,
there is a risk of an increase of the ototoxic
effect, especially if the solution is used on a
wound that is open or raw, or if the patient has
underlying kidney damage

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NOTES
Neomycin is the drug that is most toxic to
the structure involved in hearing, the
cochlea,
so it is recommended for topical use only.
But even topical therapy has resulted in
hearing loss when large areas were
treated which allowed for large amounts of
the drug to be absorbed into the body.
Hearing loss caused by this class of
antibiotics is usually permanent.

NOTES
Erythromycine usually ototoxic when given in
intravenous doses of 2-4 grams per 24 hours,
especially if there is underlying kidney failure
Diuretic are usually ototoxic when given
intravenously for acute kidney failure, acute
hypertensive crisis, or acute pulmonary
edema/congestive heart failure.
Rare cases of ototoxicity have been found when
these medications are taken orally in high doses
by people with chronic kidney disease

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EAR DISEASES
Oto vestibular disorder
Infection
Otitis externa
Otitis Media

DRUG USE IN OTO

VESTIBULAR DISEASES
Dizziness
Hallucination of movement
a subjective sensation
of postural instability or of illusory motion
VERTIGO-PRESYNCOPE-Disequilibrium

Menieres Disease

Periodic episodes of rotatory vertigo or dizziness

Fluctuating, progressive, low-frequency hearing loss
Tinnitus
Fullness/pressure

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DRUG USE
Dizziness:
Betahistine
hydrochloride

DRUG USE
Menieres Disease
Vestibulosuppressants (meclizine) decrease
symptoms, but generally only mask the vertigo by
decreasing the brain's response to vestibular input
Diuretics or diuretic-like medications
(hydrochlorothiazide) actually decrease the fluid
pressure load in the inner ear.
help prevent attacks

but do not help once an acute attack has started
Anti-inflammatory properties of steroids are helpful
in endolymphatic hydrops. ---This is probably due to
reduced endolymphatic pressure. Steroids actually
can reverse vertigo, tinnitus, and hearing loss

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DRUG USE
In an acutely Menieres Disease , management
is directed toward vertigo control.
Intravenous (IV) or intramuscular (IM) diazepam
provides excellent vestibular suppression and
antinausea effects.
Steroids can be given for anti-inflammatory effects in
the inner ear.
IV fluid support can help prevent dehydration and
replaces electrolytes.

Symptomatic Pharmacotherapy
Predominant targeted vestibular
neurotransmitters:
Cholinergic
Histaminergic
GABA neurotransmitters - negative inhibition

Vomiting center transmitters:

Dopaminergic (D2)
Histaminergic (H1)
Serotonergic (5-HT3)

Multiple classes of drugs effective

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Symptomatic Pharmacotherapy
Main classes :
Antihistaminergic - dimenhydrinate
Anticholinergics - scopolamine, meclizine
Anti-dopaminergic - droperidol
(gamma)-aminobutyric acid enhancing
(GABA-ergic) agents - lorazepam, valium

Reduce the severity of vestibular

symptoms
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Symptomatic Pharmacotherapy

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Suppressant agents :
Anticholinergics
Antihistamines
Benzodiazepines

Anti-emetic drugs

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anticholinergics
Inhibit stimulation ( exessive impulses )
from peripheral organs vestibular n.
Inhibit transmission in LVN ( lat. Vestibular
Nucleus )
Non-specific muscarine receptor
antagonist
Reversible overcompensation
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Agents not cross BBB are ineffective

Ineffective after symptoms have appeared
Scopalamine / atropine
SE :
Dry mouth
Urinary retention
Constipation

dilated pupils
sedation
confusion

C/I : BPH , closed angle glaucoma

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antihistamines
Uncertain mechanism
Central effect ( block H1-R)
Inhibiton synaptic transmission on MVN ( medial
vestibular nucleus )
Anticholinergic and sedative effects
Effective also after symptomes have appeared
Cinnarazine
promethazine / diphenhydramine - sedative
prochlorperazine / miclizine - antiemetic

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benzodiazepines
GABA modulators
Central suppression of vestibular response
Sedative , hypnotic, muscle relaxant ,
reduce anxiety
Clonazepam / lorazepam / alprazolam
SE :
Impaired vestibular compensation
Impaired memory
addiction
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Anti emetics
Dopamine block activity
Not ideal for emesis from vestibular
imbalance
Antihistamine effect promethazine ( H1R block)
Metoclopramide potent central
antiemetic, speed gastric emptying is not
effective antivertigo drug
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Sulpiride :
Selective dopamine (D2) antagonist
Low incidence of extrapyramidal
Antiemetic action
Improve blood flow, mucosal secretion in GI
Antivertigo , anti-migraine headache
Antidepressant activity ( low doses )
Antipsychotic activity ( high doses )
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New antiemetic 5-HT3 antagonist

serotonin ( 5 hydroxytryptamine subtype 3
receptor ) antagonist
Ondensetron / granisetron
Nausea and vomiting associated with
chemotherapy , post. Operation
Less effective for vestibular emesis
High cost
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Other options
Ca channel blockers :
Vestibular suppression on Ca channel in hair
cells
Flurnarazine / cinnarazine
Antihistamines and anticholinergic activity
Effective in meniers and migrane
SE : sedation , weight gain , parkinsonism

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Na channel blocker :
Affect GABA NT , glutamate antagonist
Phenytoin / nerontin / tegretol
Central nystagmus
Anticonvulsants are promising agents for
treatment vertigo ( uncertain mechanism )

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Histamine agonist :
Betahistine H1/H3 R agonist
Increase circulation to inner ear
Suppress veastibular function
Facilitation of compensation
SE : nausea , headache
Caution ; peptic dis , pheochromocytoma

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Steroids
Reduce duration of vertigo episodes
Effective in menieres , vestibular neuritis

Sypmpathomimetics
Counterbalance sedative effect of vestibular
suppressant - increase compensation
Ephedrine / amphetamine limitted use
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Acetyl- leucine
Vestibular suppresant
Rapid antivertigo effect ( IV)

Ginkgo-Biloba
Vestibular suppresant
Effective in tinnitus , improve memory

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Selective Ach antagonist

M2-R antagonist
Vestibular suppressant without SE
Little reaserch

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EAR INFECTION
ANTIBIOTIC
Especially Gram + antibiotics
Ear drop

TERIMA KASIH

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