Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The three best-described genetic polymorphisms of drug metabolism--the debrisoquin/sparteine type of oxidative polymorphism (hereafter referred to as the debrisoquin polymorphism), the polymorphism of N-acetylation, and the mephenytoin type of oxidative polymorphism--are reviewed. For all three polymorphisms, the poor-metabolizer phenotype is inherited as an autosomal recessive trait. The debrisoquin and mephenytoin oxidative polymorphisms involve defects in two separate cytochrome P450 enzymes. The prevalence of the poor-metabolizer phenotype for debrisoquin ranges between 2% and 10% for groups of various ethnic origins. The poor-metabolizer phenotype for mephenytoin comprises about 5% of the Caucasian population and about 20% of the Japanese population. N-acetyltransferase is a cytosolic enzyme whose clinical polymorphism was discovered using isoniazid as the substrate probe. The prevalence of the slow-acetylator phenotype among American and European Caucasian and American black groups is about 50%; among the Japanese it is about 10%. More than 20 agents are substrates for debrisoquin hydroxylase, about 15 for N-acetyltransferase, and 3-5 for mephenytoin. In poor metabolizers, debrisoquin can cause hypotension, and sparteine can cause blurred vision, headache, and dizziness. Clinical consequences of the slow-acetylator phenotype include increased susceptibility to systemic lupus erythematosus induced by procainamide and hydralazine, peripheral neuropathy induced by isoniazid, hydralazine, and dapsone, and sulfasalazine-induced dose-related leukopenia, nausea, vomiting, headache, and vertigo. After administration of mephenytoin, poor metabolizers have increased somnolence and intellectual impairment. Awareness of genetic polymorphisms of drug metabolism should improve understanding of interindividual variability in drug disposition and response.
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PMID:Polymorphic drug metabolism. 268 60

Neurotoxic volatile organic solvents used by house and car painters may lead to professional toxic encephalopathy after several years of exposure. The symptoms are memory impairment, fatigue, personality changes, headache and dizziness. Vestibular dysfunction was found in 55% of 113 painters examined, mainly in the form of reduced caloric vestibular reactions. No correlation between vestibular dysfunction and the duration of exposure, cerebral atrophy or intellectual impairment could be demonstrated. Vestibular examination may be helpful in detecting early changes in exposed persons and in determining more accurate safety limits for harmful chemicals.
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PMID:Vestibular dysfunction in occupational chronic solvent intoxication. 697 23

The prognosis of chronic toxic encephalopathy in former house painters was examined in a prospective study with a two-year observation period. Twenty-six patients, who at the initial examination had cerebral atrophy and/or intellectual impairment, were selected for the follow-up study. No competitive etiological factors (including alcohol) to the encephalopathy were suspected. During the two-year follow-up interval these patients were not professionally exposed to organic solvents. At the follow-up examination neurological, biochemical, neuropsychological, and neuroradiological parameters were reassessed and compared to the original findings. Generally the condition was unchanged. Slight improvements with regard to headache and dizziness were reported by some. However, the neurological status, the neuropsychological impairment, and the cerebral atrophy, did not change significantly. In three patients further deterioration was observed. It is argued that our patients suffered from a brain disorder different from presenile dementia of the Pick-Alzheimer type. Other alternative etiological entities were also excluded. Our findings indicate that long-term exposure to organic solvents may lead to a chronic brain syndrome. Once intellectual impairment and/or cerebral atrophy had developed, reversibility is not observed. Nor is further progression to be expected if exposure is stopped. Occupational exposure to organic solvents should be maximally restricted as it represents a risk of inducing invalidating brain syndromes.
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PMID:Prognosis in chronic toxic encephalopathy. A two-year follow-up study in 26 house painters with occupational encephalopathy. 731 95