The most common symptom of ototoxicity is tinnitus (tinnitus).
Conditions that increase the risk of ototoxicity:
Kidney failure
Liver failure
immune deficiency
advanced age
History of ototoxicity
Concomitant use of ototoxic agents
Noise exposure
Having previous NSIC
Collagen vascular diseases
The least ototoxic aminoglycoside(AG) is Netilmicin.
More than half of the patients with AG ototoxicity recover between 1 week and 6 months.
If there is no improvement 2-3 weeks after AG treatment is stopped, the risk of permanent damage is high.
Oscillopsia: It occurs as a result of total bilateral absence of vestibular functions. There is loss of oculomotor function.
Dihydrostreptomycin:
It has a severe cochleotoxic effect regardless of the dose.
It has no clinical use.
Streptomycin:
It is vestibulotoxic.
Vestibular symptoms occur in 60-70% of patients after 14 days of using 2 g of the drug.
Child dose is 15-30 mg/kg/day.
Gentamicin:
It is vestibulotoxic.
Kanamycin:
AG with the highest probability of unilateral hearing loss.
Cochleotoxic.
Tobramycin:
Cochleotoxic.
Amikacin:
Very little cochleotoxic, even less vestibular effect.
It can cause unilateral hearing loss.
Neomycin:
It’s very cochleotoxic.
No parenteral use.
Neomycin, streptomycin, kanamycin may show their cochleotoxic effects in the late period (1-2 weeks).
AG exert its antimicrobial effects through the 30s ribosomal subunit.
AGs:
They increase membrane permeability by binding to mitochondria and cell membrane phospholipids.
This effect causes Mg loss out of the cell and the cell dies.
In addition, aminoglycosides exert an ototoxic effect by affecting Ca-sensitive K channels.
AG also autotoxicizes with O2 radicals.
AGs show more ototoxic effects in Asians.
There is a familial predisposition to AGs.
AG toxicity
Type I cells vs. Type II cells
Basal cells relative to apical cells
Outer hair cells are more sensitive than inner hair cells.
Sensitivity to AG toxicity:
Crista ampullaris > Macular utricle > Macula sacculi
Substances that reduce AG toxicity experimentally:
Glutathione
Thyroxine
fosfomycin
α-lipoic acid
Brain-derived neurotrophic factor
Neurotrophin-3
4-methylcatechol
Insulin and transforming growth factor-a
Dizocilopine (N-methyl-D-aspartate receptor antagonist)
Salicylates
Cisplatin:
More cochleotoxic.
It is seen in 7% of patients.
Hearing loss is dose related and cumulative.
Tinnitus is transient and bilateral.
The ototoxic effect is observed 2 days after the start of treatment and resolves 7 days after the treatment is stopped.
Hearing loss is more common in children, which has been attributed to the fact that these children receive more cranial RT.
Carboplatin:
It is cochleotoxic (less).
Hearing loss is dose related and cumulative.
Hearing loss is at 8000-12000 Hz.
Agents that reduce cisplatin ototoxicity:
Lazaroids (scavengers of free O2 radicals)
sodium thiosulfate
Fosfomycin (phosphonic acid antibiotic)
Diethyldithiocarbamate
Ebselen
lipoic acid
4-methylthiobenzoic acid
Metalloenzyme inhibitors
D-methionine
vitamin B
From loop diuretics
Ethicrinic acid 0.7%
Bumetanide 1.1%
Furosemide causes 6.4% hearing loss.
Furosemide causes temporary hearing loss and Ethicrinic acid causes permanent hearing loss.
Desferroxamine:
It is used to increase urinary iron excretion in patients with thalasami major and Diamond-Blackfan anemia.
It has a 24% cochleotoxic effect.
From anti-inflammatory drugs:
Salicylates
Ibuprofen
Piroxicam can cause hearing loss and tinnitus.
The rate of ototoxicity using only a topical agent is 3.4%.
Clotrimazole, miconazole or tolnaftate can be used safely in the treatment of otomycosis.
Ciprofloxacin drops have been shown to not damage the inner ear.
Its 0.3% oflaxosintopic solution is the only topical agent approved by the FDA.
Other ototoxic agents: Kenopodium oil, carbon monoxide, carbon disulfide, arsenic, lead, mercury, potassium bromate, trichloroethylene, toluene, styrene, xylene, benzol, bisphosphonate, propanolol, bromcryptine, quinidine, cocaine, hexane, pentobarbital, methylamine anti-mandelate high dose ampicillin.
High frequency audiometry in the early diagnosis of ototoxicity in adults; In children, otoacoustic emission is used.
A decrease in the slow phase of nystagmus induced by caloric testing may indicate early vestibulotoxic exposure.
When hair cells are damaged, sensory epithelial support cells form new hair cells by mitosis and differentiation.
