Methemoglobinemia

Acute intoxication with DHBs occurs mainly by the oral route symptoms are close to those induced by phenol poisoning including nausea, vomiting, diarrhea, tachypnea, pulmonary edema, and CNS excitation with possibiUty of seizures followed by CNS depression. Convulsions are more frequent with catechol as well as hypotension due to peripheral vasoconstriction. Hypotension and hepatitis seem more frequent with hydroquinone and resorcinol. Methemoglobinemia and hepatic injury may be noted within a few days after intoxication by DHBs. 

Inhalation is the chief route of worker exposure. Comparative data from acute or subchronic inhalation exposures with rats (98) indicate that nitromethane and nitroethane are the least toxic of the nitroparaffins by this route and do not induce methemoglobin formation. The nitropropanes are less well tolerated 2-nitropropane is more toxic than 1-nitropropane and is more likely to cause methemoglobinemia. 

The compound is an intermediate in several synthetic reactions and recently has found extensive use in experimental toxicity studies in animals. It has been shown to cause methemoglobinemia its metaboHsm in humans has been discussed (189,190). 

Fth oxya ceta n i1 i de possesses both antipyretic and analgesic properties, but it is of Httie value for the reUef of severe pain. Its use for prolonged periods should be avoided because one of its minor metaboUtes ( 2-hydroxyphenetidine) is nephrotoxic and may be involved in the formation of methemoglobinemia. The oral LD q in rats is 1.65 g/kg (198). 

Prilocaine hydrochloride [1786-81-8] is also similar in profile to Hdocaine, although prilocaine has significantly less vasodilator activity. Prilocaine is the least toxic of the amino amide local anesthetics. However, its tendency to cause methemoglobinemia, especially in newborns, has eliminated its use in obstetric surgery. 

Nitrate and Nitrite. Nitrate is usually present in trace quantities in surface waters but occasionally occurs in high concentrations in some groundwaters. If present in excessive amounts, it can contribute to the illness infant methemoglobinemia. Nitrate is an essential nutrient for many photosynthetic autotrophs. Nitrite is an intermediate in the reduction of nitrate as well as in the oxidation of ammonia it is also used as a corrosion inhibitor in some industrial processes. 

R(-)-isomer rapidly hydrolyzed to toluidine (cause of methemoglobinemia)... 

Although NOT is not usually thought of as a "toxic" chemical, it does cause several health problems including methemoglobinemia in infants (blue-baby syndrome) and may also be linked to stomach cancer. Agricultural runoff can lead to significant, potentially harmful, concentrations of NOT in ground or surface water. 

In methemoglobinemia, the heme iron is ferric rather than ferrous. Methemoglobin thus can neither bind nor transport Oj. Normally, the enzyme methemoglobin... 

Methemoglobinemia Intake of excess oxidants (various chemicals and drugs) Genetic deficiency in the NADH-dependent methemoglobin reductase system (MIM 250800) Inheritance of HbM (MIM 141800)... 

Jaffe ER, Hultquist DE Cytochrome reductase deficiency and enzymopenic hereditary methemoglobinemia. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

Hydantoln anticonvulsants may cause the appearance of positive L.E. cells and methemoglobinemia. Chloropromazlne has been Implicated In causing a syndrome like systemic lupus erythematosus with accompanying positive tests for L.E. cells and antinuclear antibodies (6). 

At the moment, only three in vitro studies have been performed on Bfx metabolic behavior, hi one case, it has been shown that Bfxs are able to be reduced by oxyhemoglobin to the corresponding o-nitroaniline derivatives (Scheme 5) [237]. hi the reaction between compoimd 135 and oxyhemoglobin compound 136 was generated as secondary product resulting from both nitrile hydrolysis and deoxygenation. This study indicates that blood is a possible site for metabolism of Bfxs with the consequent methemoglobinemia. 

May precipitate a Heinz body hemolytic anemia or methemoglobinemia... 

Nitroglycerin 5-1 00 mcg/kg/minute as IV infusion 2-5 minutes 5-1 0 minutes Headache, vomiting, methemoglobinemia, tolerance with prolonged use Coronary ischemia... 

Flutamide 750 mg/day Gynecomastia Hot flushes Gastrointestinal disturbances (diarrhea) Liver function test abnormalities Breast tenderness Methemoglobinemia... 

M. Nitzan, B. Volovitz, and E. Topper, Infantile methemoglobinemia caused by food additives, Clin. Toxicol., 15, 273 (1979). 

Hereditary methemoglobinemia is classified into three types a red blood cell type (type I), a generalized type (type II), and a blood cell type (type HI). Enzyme deficiency of type I is limited to red blood cells, and these patients show only the diffuse, persistent, slate-gray cyanosis not associated with cardiac or pulmonary disease. In type II, the enzyme deficiency occurs in all cells, and patients of this type have a severe neurological disorder with mental retardation that predisposes them to early death. Patients with type III show symptoms similar to those of patients with type I. The precise nature of type III is not clear, but decreased enzyme activity is observed in all cells (M9). It is considered that uncomplicated hereditary methemoglobinemia without neurological involvement arises from a defect limited to the soluble cytochrome b5 reductase and that a combined deficiency of both the cytosolic and the microsomal cytochrome b5 reductase occurs in subjects with mental retardation. Up to now, three missense mutations in type I and three missense mutations, two nonsense mutations, two in-frame 3-bp deletions, and one splicing mutation in type n have been identified (M3, M8, M31). 

M8. Manabe, J., Arya, R Sumimoto, H., Yubisui, T., Bellingham, A. J Layton, D. M., and Fuku-maki, Y., Two novel mutations in the reduced nicotinamide adenine dinucleotide (NADH)-cy-tochrome b5 reductase gene of a patient with generalized type, hereditary methemoglobinemia. 

M31. Mota, L Kaplan, J.-C., Kahn, A., and Leroux, A., Four new mutations in the NADH-cy-tochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type H. Blood 85,2254-2262 (1995). 

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