Pharmacological Aspects

2. OTOTOXICITY
SAFDAR ALI
Consultant Audiologist
Bahawal Victoria Hospital Bahawalpur
Audiology Centre Bahawalpur
Pakistan

3.  Oto = Ear
 Toxicity = Poisoning
 Ototoxicity is quite simply, ear poisoning which
results from exposure to drugs or chemicals that
damage the inner ear or the vestibulocochlear nerve.
What is Ototoxicity?

4.  Inner ear involved in both hearing and balance
 Ototoxicity can disturb both these senses.
 It can be:-
Cochleotoxic
Vestibulotoxic
 Its effect can be
Temporary
Permanent
Types

5.  In Cochlear:
 Inner hair cells primarily affected
 In Vestibule:
 Type I hair cells of the crista of the
semicircular canals are affected
Pathophysiology

6. Pathophysiology

7.  Unilateral or Bilateral Hearing Loss (damage to high
frequencies firstly).
 Tinnitus
 Vestibular Function decrease
 Vertigo
 Gait
Clinical Manifestations of Ototoxicity

8.  Aminoglycosides
 Diuretics
 Antimalarial
 Anticancer drugs
 Analgesics
 Miscellaneous
Ototoxic Drugs

9.  It has long been known that the major
irreversible toxicity of aminoglycosides is
ototoxicity.
 Aminoglycosides appear to generate free radicals
within the inner ear, with subsequent permanent
damage to sensory cells and neurons, resulting in
permanent hearing loss.
Aminoglycosides

10.  Aminoglycosides can enter into
inner ear through
 Blood stream (when given
intravenously in largest
amount or through oral
route).
 Diffusion from middle ear
to inner ear
Aminoglycosides

11.  Cochleotoxic Aminoglycosides
 Amikacin
 Neomycin
 Dihydrosterptomycin
 Kanamycin
 Netilmicin
Aminoglycosides

12.  Vestibulotoxic Aminoglycosides
 Streptomycin
 Gentamicin
 Sisomycin
Aminoglycosides

13.  Specifically Loop diuretics are
family of ‘‘water pills” known to
occasionally cause temporary
ototoxicity.
 Bumetanide
 Ethacrynic Acid
 Furosemide
 Torsemide
Diuretics (Loop Diuretics)

14.  Drugs that use to treat malaria can be ototoxic these
drugs are
Quinine
Choloroquine
Antimalarials

15.  Anti-cancer or neoplastic drugs work by killing cancer
cells. Unfortunately some can also damage or kill cells
elsewhere in the body, including the ears.
 Cisplatin
 Carboplatin
 Nitrogen mustard
Neoplastic Drugs

16.  High doses of nonsteroidal anti-inflammatory drugs
(NSAIDs) have been shown to be ototoxic
 Aspirine
 Phenylbutazone
 Ibuprofen
 Indomethacin
Analgesics

17.  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.
Environmental Chemicals

18.  Some of these chemicals include:
> Butyl nitrite > Mercury
> Carbon disulfide > Styrene
> Carbon monoxide > Tin
> Hexane > Toluene
> Lead > Trichloroethylene
> Manganese > Xylene
Environmental Chemicals

19.  Cisplatin is an effective drug used in the treatment of
many cancers, yet its ototoxic potential places cancer
patients, exposed to this drug, at risk of hearing loss,
thus negatively impacting further on a patient’s
quality of life.
 Since its discovery Cisplatin continues to be hailed as
one of the most potent cancer chemotherapeutics in
children and adults, as it is unique and unmatched in
its effectiveness against many cancers
Ototoxicity due to Cisplatin

20. Cisplatin-associated ototoxicity usually manifests as
 Irreversible
 Progressive
 Bilateral
 High frequency sensorineural hearing loss
 Tinnitus
Clinical manifestation of Cisplatin
Ototoxicity

21.  Three Mechanisms
 Formation of ROS
 NOX3
 TRPV1
Mechanism of Action

23.  Cellular mechanism of Cisplatin associated ototoxicity
involves damage to :
 Outer hair cells
 Supporting cells
 Marginal cells of stria vascularis
 Spiral ligament
 Spiral ganglion
Cellular Mechanism

24.  Structures of the inner ear are most susceptible to
damage by Cisplatin chemotherapy. Apoptotic
degeneration of the hair cell in the organ of Corti
being most prominent.
 The outer hair cells in the basal turn of the cochlea
are most affected.
 This leads to an initial elevation of high frequency
audiometric thresholds.

25. ‘‘Ototoxicity among patients receiving Multidrug-
Resistant Tuberculosis Treatment; Experience from a
Tertiary care Hospital’’
By:
Javaid A, et al 2018
Article on Ototoxicity

26.  Multidrug-resistant tuberculosis (MDR-TB) is an
increasing challenge to health services globally.
Although new drugs are in development, current
guidelines still recommend prolonged use of
injectable antimicrobials (usually Amikacin,
Kanamycin or Capreomycin).
Background

27.  Retrospective Study
 Lady Reading Hospital Peshawar
 Jan 1, 2012 – Dec 31, 2013
 543 patients treated with injectables for MDR-TB
 Baseline Audiogram taken at time of registration for
MDR-TB treatment
Methods

28.  Out of 543 patients
467 (87.7%) received Amikacin
67 (12.3 %) received Capreomycin
Injectables used

29.  Out of 543
 200 (36.83%) patients showed evidence of
ototoxicity.
Among 200
 59 found with hearing loss
 69 having Tinnitus
 73 have both Hearing loss &
Tinnitus
Ototoxicity Outcomes

30.  Among 200 patients who showed ototoxicity
 182 (91%) receiving Amikacin injection
 18 (9%) receiving Capreomycin injection
 Ototoxicity was found to be statistically significant
(p=0.031, Odd Ratio =2.179) with both Amikacin &
Capreomycin.
Ototoxicity Outcomes

31.  MDR-TB is an increasingly common challenge in
clinical practice and current injectable therapies can
lead to substantial long-term ototoxicity. Better use
of current treatment and monitoring strategies could
reduce this.
 Administration of Capreomycin may help in reducing
risk of Ototoxicity
Conclusion

32.  No Therapy to reverse damage
 Awareness regarding ototoxic agents
 Drug monitoring during treatment
 Alternative treatment if possible
 Amplification with hearing aids or cochlear implant
to improve hearing status.
Treatment of Ototoxicity