This document discusses drug-induced vertigo (ototoxicity) caused by certain medications damaging the inner ear. The most common ototoxic drugs are aminoglycosides, loop diuretics, anti-neoplastic agents, quinine, and salicylates. Aminoglycosides like streptomycin can cause permanent hearing loss and vestibular toxicity by generating reactive oxygen species and activating caspases in hair cells. Loop diuretics may cause temporary hearing loss through changes in ionic gradients in the inner ear. Anti-neoplastic agents such as cisplatin commonly cause irreversible, progressive hearing loss through free radical production and apoptotic cell death. Risk of ototoxicity from these drugs can

1. S U N I L K U M A R D A H A
Drug Induced Vertigo
(Ototoxicity)

2. Introduction
 Any drugs with the potential to cause toxic reaction
to structure of the inner ear including the cochlea,
vestibule, semicircular canal and otoliths are called
the ototoxic drugs.
 Damage can result in hearing loss, tinnitus and
disequilibrium or dizziness.

3. Most common ototoxic drugs
1. Aminoglycosides
2. Loop diuretics
3. Anti neoplastic agents
4. Quinine
5. Salicylates

4. 1. Aminoglycosides
 Irreversible inhibitor of protein synthesis
 Effective against aerobic, gram-negative bacteria
 Drugs are:-
 Streptomycin
 Gentamicin
 Neomycin
 Kanamycin
 Amikacin
 Tobramycin

5. Predisposing factors
 Larger doses or longer duration of therapy
 Elderly patients with
 Renal insufficiency
 Preexisting hearing problems
 Family history of ototoxicity
 Receiving loop diuretics or other ototoxic or nephrotoxic
medications
 A genetic predisposition exists in mitochondrial RNA
mutation, found to be associated with
aminoglycoside-induced hearing loss

6. Pathophysiology
Enters hair cell to induce cell death
Within hair cells, drug leads to formation of reactive
oxygen species
Also activation of caspases, nucleases
Permanent loss of sensory hair cells in both cochlea
and vestibular apparatus

7. Clinical features
Acute cochlear damage may present as
tinnitus:
 Early, hearing loss: high frequencies (>4000 Hz).
 With progression: lower speech frequencies and the patient
may become profoundly deaf if the drug is continued
 The loss is usually permanent

8. Vestibular toxicity:
 This includes imbalance and visual symptoms.
 The imbalance is worse in the dark or in situations in which
footing is uncertain
 Spinning vertigo is unusual
 The visual symptoms, called oscillopsia, occur only when the
head is moving
 Quick movements of the head are associated with transient
visual blurring, so difficulty while driving or recognizing
people's faces while walking
 Clinically, nystagmus may be present as an early sign

9. Prevention
 Careful monitoring of serum drug levels and renal
function as well as hearing evaluations before,
during and after therapy.
 Identify high risk patients and select alternative
antibiotics for them.
 Instruct patient to avoid noisy environment for 6
months after therapy completion

10. 2. Loop Diuretics
 Act on ascending loop of Henle
 Used to treat CHF, renal failure, hypertension, cirrhosis
 Drugs are: Furosemide, Bumetanide, Torsemide
 Ototoxicity occurs in 6-7% of patients taking loop
diuretics
 Self limited and reversible in adults but irreversible in
neonates
 Ototoxicity depends on dose, infusion rate, history of
renal failure and co-administration of other ototoxic
agents

11. Pathophysiology
Stria vascularis is affected by changes in the ionic
gradients between endolymph and perilymph
It causes edema in the epithelial cells of stria
vascularis

12. Clinical features and prevention
C/F
 Hearing loss soon after taking the agent.
 Tinnitus and disequilibrium.
 Permanent hearing loss in those with renal failure and
receiving high doses.
Prevention
 Lowest dose possible
 Avoid rapid infusion rates
 Co-administration with other ototoxic drugs should be
avoided.

13. 3. Anti-neoplastic agents
 Anti-neoplastics are cell-cycle nonspecific alkylating
agents that insert into DNA helix and disrupts
replication.
 Cisplatin and Carboplatin
 Platinum-based compounds
 Used in gynecologic, lungs, CNS, head and neck and testicular
cancer
 Cisplatin irreversibly binds to plasma protein and can be
detected upto 6 months after completion of therapy

14. Pathophysiology
Ototoxicity is mediated by free radicals production and
cell death
Leads to mitochondrial mediated and caspase
medicated apoptic cell death
Ultimate permanent hearing loss

15. Risk factors
 High dose and increasing number of cycles
 Concurrent or past cranial irradiation
 Age extremes
 Dehydration
 Other co-administration of ototoxic agents
 Renal failure
C/F
 Tinnitus
 Bilateral, sensorineural, irreversible and progressive
hearing loss

16. Prevention
 Regular monitoring
 Avoid noisy exposure for up to 6 months
 Other medicines like
 Vit. E, D-methionine,
 iron chelators,
 N-acetyl-cysteine,
 caspase or calpain inhibitor and gene therapy can be used
in combination with platinum-based chemotherapeutic
agents.

17. 4. Salicylate
 Tinnitus: at levels within the therapeutic range (20
mg/dL [1.5 mmol/L]). This specific symptom should be
sought in all patients with potential salicylate toxicity.
 As CNS salicylate concentration increases, diminished
auditory acuity may ensue, sometimes leading to
deafness
5. Quinine:
 Deafness, impaired hearing.
 It is now no longer used due to its toxicity.

18. References
 Up to Date 21.2
 Ototoxicity related vertigo, Pubmed
(www.ncbi.nlm.nih.gov/pubmed/1242246)

19. Thank You