International Tinnitus Journal 2, 1-2 (1996) Chemically Induced or Drug Induced Tinnitus Claus-Frenz Claussen, M.D. Department of Neurootology - University E.N. T Clinic, Wiirzburg, Germany or approaching the truth about the clinical accompanying complaints include hearing disorders and F phenomenon of tinnitus from more and more tinnitus. Many patients complain of reduced hearing and possible aspects, it is important in the sense of understanding of speech. Frequent auditory complaints the old Aristotelean systematics of scientific thinking to include a high pitched noise and a sensation of ear choose various and alternating directions for regarding blockage. Diagnosis is elusive, but is eventually the phenomenon. Therefore, today I am also choosing a established. The neurotoxic complications are increased biochemical angle of view. in number and intensity when solvents are multiple in Our model of good and bad hearing, ear noise or tinnitus, number and are released in combination into the is primarily demonstrated in the dimension of physics environment. CTE is a chronic progressive disease. and modern data technology. Hearing is based on the Recently, a male patient, age 58, was seen in consultation transmission of physical sounds from the surrounding for severe tinnitus. A prior diagnosis of CTE had been world by resonance in space to the outer ear; the physical established 26 years ago, secondary to toxic inhalation amplifier of the middle ear; and finally by digital data of trichlorethylene vapors. Tinnitus was reported to have transmission from the cochlea via the hearing pathways been the initial symptom. The patient discovered the to the temporal lobe of the brain. However, the human beneficial effect of acoustical masking by placing the spirit, with all its sensory capacities, does not reside in a noise from a toy train close to the involved ear. It provided technically isolated house nor in a computer, but in a temporary relief from the constant and irritating tinnitus chemically constructed and biologically functioning noise. Today he reports tinnitus control, i.e., relief with a human body. tinnitus masker. The complaint of ear pressure was Many dysfunctions of the central nervous system, eliminated following removal of the patient from the toxic including the symptom of tinnitus can be elicited on a environment. However, the high pitch tinnitus persists. biochemical basis. For example, the toxic effect(s) of Neurotologic evaluation revealed a bilateral sensorineural solvents or the so-called untoward side effects of various hearing loss, primarily cochlear in location; and ab­ drug therapies. normalities in the early and late brain stem potentials. From an ecological as well as as neurotologic standpoint, Vestibular testing with polygraphic electronystagmo­ particularly in the past 30 years, society has become graphy (ENG) and cranio-corpo-graphy (CCG) recor­ increasingly aware of the dangers to human neurosensory dings revealed multiple abnormalities compatible with function(s) secondary to special industrial chemicals central neurotological disturbances. called solvents. A clinical syndrome has been identified, The public and professional communities should become related to this danger, called CHRONIC TOXIC ENCEPHALO­ alert to CTE. Such an awareness will result in its early PATHY (CTE) (Odkvist et aI., 1988). The onset of diagnosis and treatment; and contribute to an increase in symptoms are gradual and increase in intensity and our understanding of environmental hazards to public multiplicity of central nervous system involvement health and concept of tinnitus. Specifically, the concept following an initial and subsequent chronic exposure of and diagnosis of CTE should be expanded to include both the patient to the inhalation from the air of vapors of the the physical and chemical worlds for the evaluation and solvent(s), e.g., Trichlorethylene, Tetrachlorethane, and treatment of the symptom of tinnitus. Hexane (Gasoline), Cyclohexane, Tolluol, Styrene, It is well known among the lay public and medical! Methyl-n-butyl-ketone, Methylchloride, Dichlormethane, audiological professional communities that tinnitus may Trichlorethylene, Perch lor-ethylene, Lindan, etc. be elicited by a toxic drug overdose, e.g., Quinine and The CTE syndrome has been identified in laborers, Aspirin. Many medical treatments elicit a chemically technicians, painters as well as others who work and live induced tinnitus, i.e., iatrogenic. From a medical perspec­ in a polluted environment. The predominant complaints tive, the possibility of a toxic effect of a drug prescribed are disturbances in concentration, memory, cognition, for its pharmacologic and beneficial effect can occur. headache, drowsiness, malaise, and balance complaints Classification of drug pharmaceuticals are primarily described as unsteadiness and dizziness. Significant based on their principle actions. However, it is clear that 1 International Tinnitus Journal Vol. 2, No.1, 1996 Claussen no drug has only a single or specific effect. Chemically, Molindon, Paroxetin, Phenelzin, Protriptilin, Trazodon, extremely unlikely that any drug molecule will bind to Zimelidin, etc. only single species of molecular receptor. The number Several nonsteroidal anti-rheumatic agents may lead to of potential receptors is large in every patient receiving tinnitus as Acetyl-Salicylate, Acemetacine, Benorilate, pharmacological treatment. Even if the chemical structure Benoxaprofen, Carprofen, Chloroquine, Diclofenac, of the drug allows it to bind to only one kind of receptor, Diflunisal, Fenoprofen, Feprazon, Ibuprofen, Indonreta­ the process biochemically controlled by such receptors, cine, Isoxicam, Ketoprofen, Naproxen, D-Pe!licillamin, takes place in many different cell types and is therefore Phenylbutazon, Piroxicam, Proglumetacin, Proquazon, linked to many biochemical functions. The result is that Sulindac, Tolmetin, Zomepirac, etc. both the patient and the physician probably experience The synthetic partially modified glucocorticoide and report more than one drug effect. prednisolone may elicit tinnitus. Tinnitus is a possible Drugs are selective rather than specific in their actions, side effect of local anesthetics such as Bupivacain, because they bind more tightly to one than to a few types Tetracain, Lidocaine, etc. of other receptors. Furthermore, the receptors control Antimalarial agents are potent elicitors of tinnitus, e.g., discrete processes that have a specific effect. It is only Quinine, Quinidine, Chloroquinine, Hydroxychloro­ because of their selectivity that drugs are useful in clinical quine, etc. medicine. However, the benificial effects of drugs must Other therapeutic substances with a potential risk to elicit be routinely evaluated and correlated with their toxic tinnitus include Dihydroergotoxine, Doxylamine, oral effects. Such a correlation is in essence a monitoring sign, contraceptives, Lidoflazine, etc. reflecting the border between the desired beneficial effect Toxic substances long known to physicians to elicit and the deliterious toxic side effect. tinnitus include alcohol, Arsenum, Lead, Caffeine, When studying our phamacologic tool-box we come Marihuana, Nicotine, Mercury, etc. across a broad variety of drugs which eventually elicit This long and incoherent list of tinnitus eliciting drugs is tinnitus. That is an accompaniment of drug overdoses; so diverse that it is difficult to derive or establish one or unusually high drug retention in the body, e.g., due to single paradigm or theory for the specific chemical renal failure. Such drugs include the aminoglycoside interactions within the body as reflected by any and or antibiotics (Streptomycine, Gentamycine, Kanamycine, all of these drugs. However, clinical experience in etc.) medicine has taught that tinnitus is as significant a Other antibiotics include Amphotericine, Chlor­ symptom of human sickness as is pain and dizziness. amphenicol, Minocycline, Polymyxine B, Procain­ Furthermore, it is of interest that several of the above Penicilline, Sulfonamides, Vancomycine, etc. mentioned drugs are recommended for tinnitus treatment: Antineoplastic agents like Bleomycine, Cis-Platinum, Furosemide, Lidocaine, Amitryptiline, Carbamazapine, Carboplatinum, Methotrexate, Nitrogen Mustard, etc. Vinblastin, etc. are known for their possible side effect Scientific investigations attempting to further clarify the in the field of tinnitus. mechanism ciftinnitus production should also consider a The diuretics which may elicit tinnitus as a side effect broad spectrum of facts provided by what is known of include Acetazolamide, Bumetanide, Bendrofluazide, the specific mechanisms of action of the various chemical Clorotalidon, Diapamide, Etcrynic Acid, Furosemide, substances described above, and their biological effects. Hydrochlorthiazide, etc. They are lying in front of us like the "pieces of a puzzle". Another group of drugs which possibly may induce an Until now, the scientists have identified some of the unwanted tinnitus contains cardiac antiarhythmic drugs "pieces of the puzzle", however, they are unable to draw like Celiprolol, Quinidine, Flecainide, Lidocaine, Meto­ the conclusive sketch of the mosaic. These chemical facts prolol, Propranolol, etc. have not yet been placed into the definite puzzle of Psychopharmacological agents which may lead to tinnitus tinnitus. Tinnitus remains a great challenge to the com­ are many and include Amitryptiline, Benzodiazepine, munity of neurotologists and also to modern biomedical Bupropion, Carbamzepine, Diclofensine, Doxepin, sciences. Desipramin, Fluoxetin, Imipramin, Lithium, Melitracen, 2 .