The presence of hearing loss in two individuals without any reported history of damaging noise exposure confirms previous case reports showing that some of the population (50% in this sample) is vulnerable to the ototoxic effects of opium abuse. As shown in [Figure 1], an asymmetric hearing loss was noted in both individuals. Similar initial asymmetry has been noted by previous investigators following the use of hydrocodone, Percocet and methadone. Another noteworthy finding in the current study is the statistically significant notch noted at 4 kHz in the left ear. This effect is similar to that apparent in other types of ototoxicity where the hearing loss initially begins to appear at 4 kHz.
The percentage of population with hearing loss in the current study increased with hobby-related (58%) and occupational noise exposure (100%) and a significant interaction was apparent for ear, frequency and noise exposure group. Some agents such as cisplatin carbon disulfide and organic solventsare known to exacerbate the damage caused by excessive noise exposure. A similar interaction appears to be possible for excessive opium and noise exposure.
Possible sites of lesion
Cochlea
Patients with profound hearing loss associated with hydrocodone/acetaminophen abuse are known to benefit from cochlear implants. Such benefit suggests that the hearing loss is at least partially and initially cochlear in origin. Acute effects of opiates include decreased tone of peripheral blood vessels, decreased depth and frequency of breathing, and decreased secretion of adrenal and thyroid hormones. Chronic effects include reduced appetite and related effects of malnutrition including anemia and reduced resistance to infections. Additional chronic effects include chronic obstructive pulmonary disease with damage to the bronchi and lungs. Many of these effects can lead to poor blood flow to the cochlea or deprive the cochlea of essential nutrients leading to hearing loss.
The presence of opioid receptors has also been noted in the inner ears of rats and guinea pigs suggesting that they may serve as neurotransmitters or neuromodulators in the cochlea. More specifically opioid receptors mu-(μ) (MOP-R), delta-(δ) (DOP-R), and kappa-(ĸ)(KOP-R) are present in inner and outer hair cells. Opioids may inhibit basal adenylate cyclase activity via the μ, δ, and k opioid receptors of the cochlea.
Auditory nerve
Opioid receptors are also present in the spiral ganglion and nerve fibers in the organ of corti, suggesting the possibility of a neural hearing loss in addition to sensory or cochlear site of lesion. Opioid receptors MOP-R, DOP-R, KOP-R, and NOP-R are widely distributed in the central nervous system and in peripheral sensory and autonomic nerves. Heroin overdose has been previously associated with peripheral neuropathy.
Central auditory system
The previously described mechanisms that could disrupt the blood flow to the cochlea could also disrupt blood flow to the brain. King et al. described a 20-year-old man who suffered from a homonymous hemianopia after self-administration of heroin. Investigations revealed right occipital infarction with angiographic changes of arteritis in the posterior cerebral arteries. Niehaus and Meyer described a case of a 25-year-old heroin abuser who developed cerebral ischemic lesions. Cerebral magnetic resonance imaging revealed bilateral borderzone infarctions which were attributed to a heroin-associated vasculitis of the basal cerebral arteries. The central auditory system can also be affected due to functional reorganization of the central auditory pathways following reduced cochlear output.
Possible reasons for individual susceptibility
Oh et al. suggested that the presence of genetic factors may explain why some patients who abuse opiates develop clinical ototoxic symptoms and others do not. They speculated that a genetic mutation might give rise to selective vulnerability in hydrocodone-induced ototoxicity. Ho et al. noted that individual differences can occur due to genetic variations in drug transport proteins, drug receptors, and/or genetic polymorphisms of drug metabolizing enzymes.
Some of the case studies suggest that an extreme and sudden increase in drug consumption may also be a crucial factor in causing hearing loss in some patients and not others. Harell et al. suggested that the lack of reports of ototoxicity in similar cases may be due to the higher possibility of deaths at such high doses.
