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Aminoglycoside ototoxicity
1Clinical Pharmacist, Internal Medicine, Foothills Medical Centre, Calgary, Canada. duane.bates@calgaryhealthregion.ca
Drugs of Today (Barcelona, Spain : 1998)
|May 14, 2003
Summary
New insights into aminoglycoside ototoxicity reveal genetic predispositions and the role of reactive oxygen species. Concurrent antioxidant or iron chelator therapy may reduce drug-induced hearing loss.
Area of Science:
- Ototoxicity research
- Pharmacology
- Genetics
Background:
- Aminoglycoside antibiotics are crucial for treating bacterial infections but can cause ototoxicity (hearing and balance damage).
- Recent research has improved understanding of risk factors, mechanisms, and prevention strategies for aminoglycoside-induced ototoxicity.
- Higher doses of aminoglycosides administered once daily intravenously show clinical efficacy without increased ototoxicity compared to traditional methods.
Purpose of the Study:
- To review current knowledge on aminoglycoside ototoxicity, including genetic risk factors and preventative measures.
- To highlight the role of reactive oxygen species in aminoglycoside-induced hearing loss.
- To discuss the potential of antioxidant and iron chelator therapies in mitigating ototoxicity.
Main Methods:
- Literature review of studies published over the last 10 years on aminoglycoside ototoxicity.
- Analysis of clinical data comparing different aminoglycoside administration regimens.
- Review of experimental animal studies investigating the mechanisms of ototoxicity and potential interventions.
Main Results:
- Genetic mutations, specifically an A-to-G substitution in mitochondrial ribosomal ribonucleic acid (RNA) at position 1555 and a thymidine deletion in the 12s ribosomal RNA gene, are linked to increased susceptibility to aminoglycoside ototoxicity.
- Experimental data strongly suggest that reactive oxygen species are key mediators of aminoglycoside-induced ototoxicity.
- Animal studies indicate that co-administration of antioxidant or iron chelator therapy with aminoglycosides can decrease drug-induced hearing loss.
Conclusions:
- Understanding genetic predispositions and the role of reactive oxygen species is crucial for preventing aminoglycoside ototoxicity.
- Once-daily high-dose intravenous aminoglycoside administration is a safe and effective regimen.
- Antioxidant and iron chelator therapies show promise as preventative strategies against aminoglycoside-induced hearing damage.