Understanding Drug-Induced Ototoxicity

Introduction

Drug-induced ototoxicity is a significant problem in medical practice due to its possibility to induce injury to the inner ear structures and subsequent hearing loss, tinnitus, and equilibrium or balance disturbances. Ototoxicity can result from the immediate toxic effects of certain medications on the cochlea and vestibular system or through indirect pathways involving oxidative stress, inflammation, and disturbance of cellular processes. This article aims to provide an overview of drug-induced ototoxicity, its mechanisms, common drugs associated with ototoxic effects, and clinical manifestations.

What Is Ototoxicity?

Ototoxicity is a term used to describe the undesired impacts caused by certain drugs or medications, which can result in reversible or irreversible injury to the structures of the inner ear, including the cochlea and vestibule. Tinnitus can occur either concurrently with hearing loss or independently, and it may also arise from drug-induced changes in the central auditory system.

Vestibular injury can give rise to balance-related issues, such as instability, difficulties in maintaining proper posture, shakiness, loss of balance, and dizziness. The odds of experiencing ototoxic effects are influenced by various factors, including the duration of treatment, the method of drug administration, the rate of infusion, the dosage, individual sensitivity, genetic predisposition, and impaired kidney and liver functions. While single doses of medications can have ototoxic effects, the risk is greater when undergoing long-term therapy.

What Are Different Ototoxic Drugs?

Different drugs that have ototoxicity as a side effect are as follows:

1. Anti-infection Drugs:

• Antibiotics: Aminoglycosides (Neomycin, Gentamicin, Amikacin, Netilmicin), Macrolides (Erythromycin, Azithromycin, Clarithromycin), Quinolones (Ofloxacin, Ciprofloxacin, Levofloxacin), and others.

• Antivirals: Ganciclovir, Zalcitabine, Ribavirin plus Interferon.

• Antifungals: Amphotericin, Flucytosine.

• Antimalarials: Chloroquine, Mefloquine, Quinine.

• Antituberculous: Capreomycin.

2. Analgesics and Anti-inflammatory Drugs:

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Aspirin, Indomethacin, Ibuprofen, Diclofenac, and others.

• Anti-inflammatory Drugs: Ketorolac, Sulindac, Naproxen, Celecoxib.

3. Anticancer Drugs:

• Cytotoxics: Platinum compounds (Cisplatin, Carboplatin), Vinca alkaloids (Vindesine, vinblastine, Vincristine), and others.

• Others: Bexarotene, Taxane.

4. Cardiac and Vascular Drugs:

• Diuretics: Loop diuretics (Frusemide, Bumetanide, Torasemide), Carbonic anhydrase inhibitor (Acetazolamide).

• Beta-Blockers: Metoprolol, Sotalol, Practolol, Bisoprolol.

• ACE inhibitors: Ramipril.

5. Neurologic Drugs:

• Anticonvulsants: Sodium valproate.

• Anti-Parkinson's: Entacapone.

• Others: Tacrolimus.

6. Endocrine and metabolic:

• Hypoglycemics: Glipizide, Glimepiride, Pioglitazone, Insulin.

• Corticosteroids: Dexamethasone, Fludrocortisone.

• Bisphosphonates: Pamidronate, Zoledronate.

7. Gastrointestinal drugs:

• Antiemetics: Metoclopramide, Ondansetron, Nabilone, Trifluoperazine, Tropisetron.

• Antiulcer H2 Antagonists: Ranitidine, Cimetidine, Famotidine.

• Proton Pump Inhibitors: Omeprazole, lansoprazole, Pantoprazole.

• Inhibitors: Promethazine, Cetirizine, Cyclizine.

8. Lipid regulating: Fenofibrate, Simvastatin, Colestipol.

9. Other Categories:

• Immunosuppressants: Tacrolimus.

• Anti Rheumatoid: Hydroxychloroquine.

• Local Anesthetics: Ropivacaine.

• Anti-Gout: Allopurinol

• Antihistamines: Chlorpheniramine, Fexofenadine, Promethazine, Cetirizine, Cyclizine.

• Antimuscarinics: Atropine, Hyoscine, Dicyclomine.

• Antiasthmatics: Salbutamol, Montelukast, Salmeterol.

What Are the Signs and Symptoms of Drug-Induced Ototoxicity?

Pharmaceutically induced ototoxicity can lead to various effects on the auditory system, as well as the nasal and throat regions, resulting in different clinical signs and symptoms specific to these areas. The list encompasses prevalent indications and manifestations of drug-induced ototoxicity within the framework of disorders related to the ear, nose, and throat.

1. Ear-related Symptoms:

• Hearing Loss: Hearing loss can be either partial or complete impairment of auditory function, which can be temporary or permanent.

• Tinnitus: Perception of ringing, buzzing, and hissing sounds in the ears.

• Vertigo: A sensation of spinning or dizziness which causes difficulty in balancing.

• Ear Pain: Discomfort, tenderness, or pain in the ear.

2. Nose-related Symptoms:

• Nasal Congestion: Blockage or stuffiness in the nasal passages.

• Rhinorrhea: Excessive nasal discharge or a runny nose.

• Sinusitis: Inflammation or infection of the sinuses, leading to facial pain, pressure, or headaches.

3. Throat-related Symptoms:

• Sore Throat: Discomfort, pain, or irritation in the throat.

• Dysphagia: Difficulty or pain while swallowing.

• Hoarseness: Abnormal voice changes, resulting in a raspy or strained vocal quality.

• Throat Irritation: Sensation of itching, tickling, or a persistent feeling of lumping in the throat.

What Is the Diagnosis of Drug-Induced Ototoxicity?

The diagnosis of drug-induced ototoxicity involves several steps and assessments:

1. Medical History: The healthcare provider will gather information about the patient's medical history, which will include any medications the patient is currently taking or has taken in the past that are known to have potential ototoxic effects.

2. Symptoms Evaluation: Along with medical history, the doctor will also inquire about the patient's symptoms related to impaired hearing, tinnitus (persistent ringing sensation in the ears), dizziness, or imbalance will be assessed. The timing of symptom onset of drug therapy will also be considered.

3. Audiological Evaluation: Pure tone audiometry (PTA) is commonly performed to assess hearing sensitivity. The patient listens to tones at increasing or decreasing frequencies and volumes, and the responses will help to determine the hearing thresholds.

4. Additional Tests: Depending on the specific symptoms and findings, further tests may be conducted. Other tests can include otoacoustic emissions (OAE) to evaluate the functioning of the inner ear and its integrity, auditory brainstem responses (ABR) to evaluate the auditory nerve and brainstem pathways, and vestibular function tests to assess balance and dizziness.

5. Comparison with Baseline Data: If available, previous audiometric records or baseline assessments may be compared with the current results to identify any changes or deterioration in hearing function.

6. Evaluation of Other Causes: Other potential causes of hearing loss or related symptoms, such as underlying medical conditions or concurrent factors, will be considered and evaluated to rule out alternative explanations.

What Are the Treatment Options for Drug-Induced Ototoxicity?

Different treatment strategies are as follows:

1. Discontinuation or Modification of Medication: Upon identification of the ototoxic drug, healthcare providers may opt to discontinue its use or adjust the dosage to mitigate further harm.

2. Supportive Care: Specific symptomatic relief measures, such as pharmacological interventions or targeted therapies, may be employed to manage individual symptoms like dizziness or tinnitus.

3. Monitoring and Auditory Rehabilitation: Regular monitoring of auditory function is essential to gauge the progression of ototoxicity and determine appropriate interventions. Hearing aids or other assistive devices may be recommended to enhance hearing capabilities and improve quality of life.

4. Antioxidant Therapy: Experimental evidence suggests that high-dose antioxidant treatments could safeguard inner ear structures against damage. Consequently, the implementation of such therapies may be contemplated to counteract the detrimental effects of ototoxicity.

5. Experimental and Prospective Treatments: Ongoing research endeavors encompass regenerative therapies, including the application of stem cells, to restore damaged hair cells and enhance auditory function. Nevertheless, these treatments remain in the experimental stage and are not yet widely accessible.

Conclusion

Healthcare providers must remain cognizant of medications' potential audio-vestibular side effects. This guide proves to be an invaluable resource for quickly identifying and understanding these side effects, including hearing loss, tinnitus, dizziness, and vertigo. Regular updates to the guide are necessary to incorporate new evidence and reports. By staying informed and vigilant, healthcare professionals can better monitor and manage these side effects, ensuring the safety and well-being of their patients.