Ototoxicity as a Side-Effect of Drugs: Literature Review

Vocabulary flashcards covering key terms, mechanisms, drug classes, genetic predispositions, and diagnostic procedures related to drug-induced ototoxicity from the review article.

Ototoxicity

A functional disorder and cellular degeneration of inner ear tissues caused by therapeutic agents, leading to hearing loss and/or vestibular dysfunction manifested as tinnitus or dizziness.

Organ of Corti

The sensory structure located within the inner ear lined with hair cells that convert mechanical sound waves into neural impulses transmitted via the eighth cranial nerve.

Aminoglycoside Antibiotics (AGs)

A class of antibacterial drugs that bind permanently to the $30S$ ribosomal subunit to disrupt protein synthesis, commonly causing permanent ototoxicity targeting cochlear and vestibular hair cells.

1555A>G Mutation

An adenine-to-guanine point mutation at nucleotide 1555 in the mitochondrial $12S$ rRNA gene ($MTRNR1$) that strongly predisposes individuals to aminoglycoside-induced deafness.

C1494T Mutation

A mitochondrial $12S$ rRNA gene mutation that increases inherited susceptibility to aminoglycoside ototoxicity.

Cisplatin

A platinum-based cytostatic chemotherapeutic agent that causes progressive, irreversible, bilateral high-frequency hearing loss, often accompanied by tinnitus and dizziness.

NOX3

An NADPH oxidase isoform in the inner ear activated by cisplatin, generating reactive oxygen species and toxic 4-hydroxynonenal aldehyde that lead to hair cell apoptosis.

TRPV1

Transient receptor potential vanilloid 1 channel receptor in cochlear hair cells, activated by cisplatin to increase intracellular calcium and induce downstream $NOX3$ and $STAT1$ signaling.

STAT1

Signal transducer and activator of transcription 1, a transcription factor activated downstream of $TRPV1$ during cisplatin administration that leads to apoptotic hair cell death.

Loop Diuretics

A class of diuretic medications acting on Henle's loop that inhibit $Na^+$, $K^+$, and $Cl^-$ cotransport, causing edema of the stria vascularis and reversible or permanent hearing loss.

Furosemide

The first loop diuretic approved by the FDA in 1966, which became the primary diuretic of choice due to its lower ototoxicity compared to ethacrynic acid.

Ethacrynic Acid

A highly ototoxic loop diuretic approved in 1967 that causes rapid ischemia by abolishing blood flow in the lateral wall of the cochlea and eliminating endothelial potentials.

Chloroquine (CQ)

An antimalarial and immunomodulatory drug that accumulates in melanocyte-rich inner ear tissues, potentially causing sensory and neural hearing loss, tinnitus, and vestibular dysfunction.

Hydroxychloroquine (HCQ)

An analogue of chloroquine used for treating malaria and autoimmune conditions (such as rheumatoid arthritis and lupus) that carries a risk of temporary or permanent ototoxicity.

Ototoxicity Monitoring

The systematic, early identification of changes in hearing test parameters to detect drug-induced auditory damage before loss progresses into the speech frequency range.

High-Frequency Audiometry (HFA)

An air-conduction threshold test evaluating frequencies above $8BC$ (up to $16BC$ or $20BC$), serving as the most sensitive diagnostic tool for early detection of drug-induced cochlear damage.

Distortion Product Otoacoustic Emissions (DPOAEs)

An objective measure of outer hair cell function utilizing two simultaneous stimuli of different frequencies, capable of detecting ototoxic damage earlier than conventional audiometry.

Auditory Brainstem Response (ABR)

An electrophysiological test assessing neural activity along the auditory pathway, used for ototoxicity monitoring in uncooperative, comatose, or infant patients.

NCI CTCAE Ototoxicity Grades

A 4-degree grading scale established by the National Cancer Institute to categorize the severity of drug-induced threshold shifts and guide therapeutic intervention.

Brock's Hearing Loss Grades

A 5-level pediatric grading scale (Degrees 0 to 4) based on specific frequency cutoffs ($1\text{--}8BC$) at threshold shifts of $40BC$ or greater, used to evaluate platinum-induced ototoxicity.