Structure side-effect sorting of drugs. VI. Ototoxicities

Area of Science:

• Ototoxicology
• Pharmacology
• Cellular Biology

Background:

• A literature survey identified over 130 drugs and chemicals (7.8%) associated with ototoxicities.
• Major drug classes implicated include antibiotics, anti-inflammatories, antimalarials, beta-blockers, antineoplastics, heavy metals, and diuretics.

Purpose of the Study:

• To review and discuss the known ototoxic drugs and chemicals.
• To explore the potential mechanisms underlying drug-induced ototoxicity.
• To investigate the relationship between the chemical structure of aminoglycosides and their ototoxic potential.

Main Methods:

• Comprehensive literature survey on ototoxic drugs and chemicals.
• Analysis of proposed mechanisms of ototoxicity at the cellular level.
• Comparative analysis of five aminoglycosides regarding ototoxicity and reactivity with mucopolysaccharides.

Main Results:

• Identified major classes of ototoxic agents and their prevalence.
• Detailed potential mechanisms including mitochondrial dysfunction (inhibition of protein synthesis, metabolic cycles, energy generation, respiratory system) and alterations in endolymphatic membrane permeability or aminoglycoside excretion.
• Found a correlation between the number of basic groups in aminoglycoside molecules and their relative rank order of ototoxicity and reactivity toward mucopolysaccharides.

Conclusions:

• A significant number of common drugs and chemicals pose a risk of ototoxicity.
• Ototoxicity mechanisms are multifaceted, involving critical cellular processes within cochlear hair cells and ion transport systems.
• The chemical structure, specifically the number of basic groups, influences the ototoxic potential of aminoglycoside antibiotics.