Nervous system toxicity peripheral neuropathies

Peripheral neuropathy has also occurred in humans as the result of solvent abuse of products containing -hexane (Altenkirch et al. 1977 Chang et al. 1998 Spencer et al. 1980). Clinical signs were very similar to those seen after occupational exposure however, signs of central nervous system toxicity may also be present due to other components in the inhaled mixtures, e.g., toluene (Spencer et al. 1980). 

Neurological examinations of humans with M-hexanc-induced peripheral neuropathy have not shown clinical signs of central nervous system toxicity (Herskowitz et al. 1971 Yamamura 1969). There have been reports of altered evoked potentials recorded in the brain (increased latency, decreased amplitude) in humans occupationally exposed to -hexane (Mutti et al. 1982c Seppalainen et al. 1979). There has been one report of an individual occupationally exposed to -hexane for 38 years who developed Parkinsonism (Pezzoli et al. 1995), although the etiology of this case is complicated by the fact that the patient had a sister who was probably affected by Parkinsonism. Further studies, particularly prospective... 

Peripheral neuropathy is observed in 10-20% of patients given dosages greater than 5 mg/kg/d, but it is infrequently seen with the standard 300-mg adult dose. Peripheral neuropathy is more likely to occur in slow acetylators and patients with predisposing conditions such as malnutrition, alcoholism, diabetes, AIDS, and uremia. Neuropathy is due to a relative pyridoxine deficiency. Isoniazid promotes excretion of pyridoxine, and this toxicity is readily reversed by administration of pyridoxine in a dosage as low as 10 mg/d. Central nervous system toxicity, which is less common, includes memory loss, psychosis, and seizures. These may also respond to pyridoxine. 

Nervous system Fluorouracil can cause acute nervous system toxicity. Acute cerebellar syndrome affects up to 5% of patients and is usually self-limiting after withdrawal. It can occur within weeks to months of starting fluorouracil and presents with ataxia, nystagmus, and dysarthria [77, 78 ]. An encephalopathy can occur rarely and is often associated with markedly raised ammonia concentrations in the absence of underlying liver disease. Ischemic stroke has also been reported and the risk appears to be increased when fluorouracil is combined with cisplatin [60, 79 ]. Other rare adverse reactions include oculomotor disturbances, focal dystonia, parkinsonian syndrome, peripheral neuropathy, and seizures [80 ]. Dihydropyrimidine dehydrogenase deficiency also increases the risk of nervous system toxicity [81" ]. 

The main dose-limiting toxicity is neurotoxicity, usually expressed as a peripheral sensory neuropathy, although autonomic nervous system dysfunction with orthostatic hypotension, urinary retention, paralytic ileus, or constipation, cranial nerve palsies, ataxia, seizures, and coma have been observed. While myelosuppression occurs, it is generally milder and much less significant than with vinblastine. The other potential adverse effect that can develop is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). 

Lead is a toxic metal to which there is wide exposure. Exposure is via inhalation (main source, leaded petrol) and ingestion (water, old paint). Multi-organ toxicity occurs with the kidneys, central and peripheral nervous system, testes, red cells, bones, and gastrointestinal tract all damaged. After initial distribution into red blood cells, it is eventually deposited in bone. The main biochemical effect is interference with heme synthesis at several points. Kidney toxicity may be due to lead-protein complexes and inhibition of mitochondrial function. Damage to nerves leads to peripheral neuropathy. 

As its name implies, peripheral neuropathy refers to damage to nerves outside the central nervous system. It is especially evident as damage to the motor nerves involved with voluntary muscle movement. Victims of peripheral neuropathy often have problems with movement and are afflicted with symptoms such as foot drag or Jake leg, a malady that got its name from toxic effects of contaminated Jamaican ginger. 

Herbicides, or weed killers, may be classified as pesticide chemicals. They can kill plants on contact, or they can be translocated (i.e absorbed by one part of the plant and carried to other parts where they exert their primary toxic effect). Most commonly used herbicides have a low toxicity and have caused few adverse effects in users. Some herbicides pose more serious problems to the central nervous system (CNS) and can cause depression. The skin absorption of herbicides also may cause skin irritation, dermatitis, and photosensitization in addition to peripheral motor neuropathies. 

GI pain and bleeding pulmonary edema anemia, destruction of red blood cells liver necrosis, kidney failure encephalopathy and other central and peripheral nervous system disorders. Chronic toxicity can lead to systemic hypotension skin disorders such as eczema, hyperkeratosis, melanosis, ulceration, skin cancers blood problems such as anemia, acute leukemia kidney failure delirium, encephalopathy, seizures, neuropathy. 

The acute toxicity from overexposure to petroleum ether is manifested primarily in central nervous system (CNS) effects. The mechanism of toxicity is unknown however, the general anoxia observed is most likely due to oxygen deprivation. The mechanism of toxicity from long-term overexposure to petroleum ether is dependent on the chemical makeup of the distillate. For example, if peripheral neuropathy is observed, it is most likely due to a high concentration of -hexane in the petroleum ether. -Hexane is known to cause axonal damage in peripheral nerves. 

Chlorophenoxy herbicides are, by themselves, of relative low toxicity to humans. They are, however, often contaminated with dioxins, of which, 2,3,7,8-tetrachloro-p-dioxin (TCDD) is the most toxic, which cause CNS and peripheral nervous system neuropathies. l8l... 

Factors that inhibit or alter the activity of the mixed function oxidase enzymes may increase the risk from exposure to the indicator compounds in the aromatic EC5-EC9 fraction (the BTEXs), the aromatic EC>16-EC35 fraction (the carcinogenic PAHs in this fraction) and a constituent of the aliphatic I < C5IiCH fraction (//-hexane). For example, concurrent alcohol consumption may increase the risk of central nervous system depression from the BTEXs, ototoxicity from toluene, and hematotoxicity from benzene. Acetone exposure may increase the risk of peripheral neuropathy of n-hexane. People who take haloperidol, acetaminophen, or aspirin, or who have a nutritionally inadequate diet, may also be more susceptible to the toxicity of these agents. ATSDR (1995f) noted that a substantial percentage of children consume less than the recommended dietary allowances of certain nutrients. 

For recent skin-test converters of all ages, the risk of active TB outweighs the risk for drug toxicity.Pregnant women, alcoholics, and patients with poor diets who are treated with isoniazid should receive pyridoxine (vitamin Bg) 10-50 mg daily to reduce the incidence of central nervous system (CNS) effects or peripheral neuropathies. All patients who receive treatment of LTBl should be monitored monthly for adverse drug reactions and for possible progression to active TB. 

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