Question

Enumerate various ototoxic drugs with their mechanism of action for producing ototoxicity.

Hint:

Combination therapy with ototoxic drugs should be closely monitored to prevent irreversible hearing loss, especially in patients at risk or those receiving high doses.

Answer 1

Step 1: Definition of Ototoxic Drugs.
Ototoxic drugs are medications that can cause damage to the inner ear, leading to hearing loss and/or balance disorders. This occurs when these drugs affect the cochlear cells, auditory nerve, or vestibular system. The ototoxic effect may be dose-dependent and can either be temporary or permanent. The mechanisms of action vary depending on the drug.

Step 2: Types of Ototoxic Drugs and Their Mechanisms of Action.
1. Aminoglycoside antibiotics (e.g., gentamicin, tobramycin, amikacin):
- Mechanism of Action: Aminoglycosides inhibit bacterial protein synthesis, but they also cause damage to the cochlear and vestibular hair cells by accumulating in the inner ear. They bind to the cell membranes of cochlear cells, leading to oxidative stress, apoptosis, and cellular damage. 2. Loop diuretics (e.g., furosemide, bumetanide):
- Mechanism of Action: Loop diuretics inhibit the reabsorption of sodium and chloride in the kidneys, but they can also disrupt the ion balance in the inner ear. This can lead to altered fluid dynamics in the cochlea and damage to the hair cells, especially when used at high doses or in combination with other ototoxic drugs. 3. Chemotherapy agents (e.g., cisplatin, carboplatin):
- Mechanism of Action: These drugs interfere with DNA replication in cancer cells, but they can also accumulate in cochlear cells, leading to oxidative damage and apoptosis. Cisplatin is especially toxic to the cochlea and can cause permanent hearing loss. 4. Salicylates (e.g., aspirin):
- Mechanism of Action: High doses of salicylates can cause reversible tinnitus and hearing loss by increasing the levels of nitric oxide in the cochlea, which can damage the hair cells and auditory nerve fibers. 5. Quinine (used to treat malaria):
- Mechanism of Action: Quinine is believed to cause ototoxicity by directly damaging the cochlear cells and causing an increase in reactive oxygen species, leading to oxidative stress and cellular injury. 6. Antimalarial drugs (e.g., chloroquine, hydroxychloroquine): - Mechanism of Action: These drugs accumulate in the inner ear and are believed to affect the cochlear cells through mechanisms similar to quinine, leading to hearing loss and balance dysfunction.

Step 3: Conclusion.
Ototoxic drugs are widely used but carry the risk of damaging the inner ear. Understanding their mechanisms of action helps in identifying and managing ototoxicity. Close monitoring of hearing function is important when these drugs are used.