Peripheral nervous system alcoholism

Although now largely eradicated, beriberi remains a problem in some parts of the world among people whose diet is especially high in carbohydrates. A different condition, affecting the central rather than peripheral nervous system, the Wemicke-Korsakoff syndrome, is also due to thiamin deficiency. It occurs in developed countries, especially among alcoholics and narcotic addicts. 

Papp A, Pecze L, Vezer T. Acute effects of lead, mercury and manganese on the central and peripheral nervous system in rats in combination with alcohol exposure. ArhHigRada Tokiskol2005 56(3) 241 8 [abstract only—PubMed]. 

Beriberi, a neurologic and cardiovascular disorder, is caused by adi etary deficiency of thiamine (also called vitamin B,). The disease has been and continues to be a serious health problem in the Far East because rice, the major food, has a rather low content of thiamine. This deficiency is partly ameliorated if the whole rice grain is soaked in water before milling some of the thiamine in the husk then leaches into the rice kernel. The problem is exacerbated if the rice is polished, because only the outer layer contains significant amounts ot thiamine. Beriberi is also occasionally seen in alcoholics who are severely malnourished and thus thiamine deficient. The disease is characterized by neurologic and cardiac symptoms. Damage to the peripheral nervous system is expressed as pain in the limbs, weakness of the musculature, and distorted skin sensation. The heart may be enlarged and the cardiac output inadequate. 

Because of its chemical solubility properties, alcohol easily penetrates all cells and tissues in the body. It s a neurotoxin for the central and peripheral nervous systems, a hepatotoxin for the liver, a nephrotoxin for the kidney. It can interact chemically with any biological cell, including a progenitor cell in an embryo it can kill that cell and the entire lineage that would develop from it during embryonic development. 

Many alcoholics such as Al Martini develop thiamine deficiency because alcohol inhibits the transport of thiamine through the intestinal mucosal cells. In the body, thiamine is converted to thiamine pyrophosphate (TPP). TPP acts as a coenzyme in the decarboxylation of a-keto acids such as pyruvate and a-ketoglutarate (see Fig. 8.11) and in the utilization of pentose phosphates in the pentose phosphate pathway. As a result of thiamine deficiency, the oxidation of a-keto acids is impaired. Dysfunction occurs in the central and peripheral nervous system, the cardiovascular system, and other organs. 

C HjjNOj, Mr 289.37, needles, mp, 106-108 °C, [ain -22° (50% C2H5OH/H2O), A tropane alkaloid form numerous Solanaceae genera such as, e.g. Atropa (deadly nightshade). Datura (thorn apple), Du-boisia, Hyoscyamus (henbane), and Scopolia (banewort). H. racemizes slowly in alcoholic solution, rapidly in alkaline and acidic solutions and in molten state to atropine. It has the same effects on the central nervous system as atropine and a twice as strong toxic effect on the peripheral nervous system [LD50 (mouse i. V.) 95 mg/kg]. Symptoms of poisoning include dry mouth and throat. For isolation from cell cultures, see Lit. For biosynthesis, see tropane alkaloids. 

Neurotoxins Agents that produce damage to the central and/or peripheral nervous system. Examples of neurotoxins include carbon monoxide, lead, methyl mercury, cyanide, alcohols, and others. 

Historically, thiamin deficiency affecting the peripheral nervous system (beriberi) was a major public health problem in South-East Asia following the introduction of the steam-powered mill that made highly polished (thiamin-depleted) rice widely available. There are still sporadic outbreaks of deficiency among people whose diet is rich in carbohydrate and poor in thiamin. More commonly, thiamin deficiency affecting the heart and central nervous system is a problem in people with an excessive consumption of alcohol - to the extent that there was it was seriously suggested in Australia at one time that thiamin should be added to beer. 

Neuropathic pain is initiated or caused by a primary lesion in the peripheral or central nervous system. The causative agent may be trauma, nerve-invading cancer, herpes zoster, HIV, stroke, diabetes, alcohol or other toxic substances. Neuropathic pain is refractory to most analgesic drugs. Altered sodium channel activity is characteristics of neuropathic pain states. 

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. 

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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