Vestibular toxicity

Tetracyclines are used as alternative dnigs in a variety of circumstances when the patient is unable to take the dnig of choice, eg, in patients allergic to penicillin (88,89). Tetracyclines are widely known to cause staining of teeth (and are therefore contra-indicated in children developing permanent teeth), photosensitivity, and, in the case of minocycline, vestibular toxicity. Details of these adverse effects and others associated with administration of tetracyclines have been comprehensively reviewed (96—101). 

Minocycline Tablets, capsules 50, 75, 1 00 mg 50 mg twice daily or 100 mg once daily Maintenance dose 50 mg daily Gl upset, phototoxicity, drug and food interactions, vestibular toxicity, skin discoloration... 

Aminoglycosides accumulate in otolymph and can cause both vestibular and auditory ototoxicity, both of which can be irreversible. Uptake is driven by the concentration gradient between blood and the otolymph this process is saturable. Sustained high concentrations in otolymph first destroy hair cells that are sensitive to high-frequency sounds. Streptomycin is more likely to cause vestibular toxicity than ototoxicity. The severity... 

Minocycline Oral longer half-life (16 h) so dosed twice daily frequently causes reversible vestibular toxicity... 

Pain at the injection site is common but usually not severe. The most serious toxic effect with streptomycin is disturbance of vestibular function—vertigo and loss of balance. The frequency and severity of this disturbance are in proportion to the age of the patient, the blood levels of the drug, and the duration of administration. Vestibular dysfunction may follow a few weeks of unusually high blood levels (eg, in individuals with impaired renal function) or months of relatively low blood levels. Vestibular toxicity tends to be irreversible. Streptomycin given during pregnancy can cause deafness in the newborn and therefore is relatively contraindicated. 

Vestibular toxicity appears to be unique to minocycline. Lightheadedness, loss of balance, dizziness, nausea, and tinnitus beginning 2 to 3 days after starting therapy can occur in up to 70% of patients. Although these side effects are usually reversible after discontinuing the drug, they have severely limited the use of minocycline. 

In 40 patients tobramycin had little effect on audiometric thresholds, but produced a change in the amplitude of the distortion products, currently considered an objective method for rapidly evaluating the functional status of the cochlea (17). In one case, tobramycin caused bilateral high-frequency vestibular toxicity, which subsequently showed clinical and objective evidence of functional recovery (18). 

Clinically, cochlear ototoxicity is more frequent and easier to detect than vestibular toxicity combined defects are relatively rare. Symptoms of cochlear damage include tinnitus, hearing loss, pressure, and sometimes pain in the ear. The manifestations of vestibular toxicity are dizziness, vertigo, ataxia, and nystagmus. These are often overlooked in severely ill, bed-ridden patients. 

Bolus intraperitoneal gentamicin or tobramycin (5 mg/kg ideal body weight) is safe, achieves therapeutic blood concentrations for extended intervals, causes no clinical ototoxicity or vestibular toxicity, is cost-effective, and is convenient for patients and nurses (170). 

Walsh RM, Bath AP, Bance ML. Reversible tobramycin-induced bilateral high-frequency vestibular toxicity. ORL J Otorhinolaryngol Relat Spec 2000 62(3) 156-9. 

Caston J, Doinel L. Comparative vestibular toxicity of dibekacin, habekacin and cisplatin. Acta Otolaryngol 1987 104(3 ) 315-21. 

An adolescent with cystic fibrosis developed renal insufficiency and severe vestibular toxicity after treatment with gentamicin and standard-dose ibuprofen (72). A low intravascular volume was a possible contributing factor. 

Isepamicin is similar to amikacin but has better activity against strains that produce type I 6 -acetyltransferase. It can cause nephrotoxicity, vestibular toxicity, and ototoxicity. However, it is one of the less toxic of the aminoglycosides (1). The antibacterial spectrum of isepamicin includes Enterobacteriaceae and staphylococci anaerobes, Neisseriae, and streptococci are resistant (1). Isepamicin was as effective and safe as amikacin in the treatment of acute pyelonephritis in children and might prove an advantageous alternative in areas with a high incidence of resistance to other aminoglycosides (2). 

Kanamycin causes mainly cochlear damage (2). After prolonged administration (for example 1 g for periods of 30-180 days) the frequency of this adverse reaction is higher than 40%. Vestibular toxicity occurs in less than 10% of cases treated with usual doses and is generally reversible soon after withdrawal. 

Streptomycin occasionally causes nephrotoxicity, although it tends to be mild and reversible. It also is capable of causing ototoxicity (vestibular and cochlear), which may become permanent with continued use. Older patients and those receiving long durations of treatment are most likely to experience hearing loss, whereas vestibular toxicity is highly unpredictable. 

Vestibular toxicity Dose-dependent reversible dizziness and vertigo have been reported with doxycycUne and minocycline. 

It is less dependent on active uptake mechanisms and has a somewhat broader antimicrobial spectrum. It also, apparently, is less painful on IM or IV injection, but it has vestibular toxicities (e.g., vertigo, ataxia, and nausea) not generally shared by other tetracyclines. 

Susceptibility factors for the development of ototoxicity in adult patients with cystic fibrosis have been reviewed in a retrospective cohort study in 39 patients, of whom seven had evidence of ototoxicity, four had cochlear toxicity, two had vestibular toxicity and one had evidence of both [8 ]. In a multivariate analysis, ototoxicity was predicted by trough serum concentrations over lOmg/1 for amikacin and over 2 mg/1 for gentamicin and tobramycin (OR=45 95% 0=3.1, 655). 

Data on the mechanisms of vestibular toxicity and its development in association with aminoglycoside exposure have been extracted from the MEDLINE database and summarized [2 ]. For similarly designed studies the pooled incidence of vestibular toxicity was 11% for gentamicin, 7.4% for amikacin, 3.5% for tobramycin, and 1.1% for netilmicin. The underlying mechanism appears to be excessive production of oxidative free radicals, a time-dependent mechanism, but not apparently related to dose or serum concentration. 

Relatively few toxicants produce primary cerebellar or vestibular sigris. One group of vestibular toxicants important in veterinary medkine are tfie aminoglycoside antibiotics. 

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