Methemoglobinemia Methemoglobin reductase

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)... 

Methemoglobinemia has long been associated with the absence of an NADH-linked diaphorase 362, 363). However, flavoproteins isolated from the red cell were never sufficiently active to account for the methemoglobin reductase activity calculated to be necessary. It has now been shown that a methemoglobin reductase system of high activity is composed of soluble forms of cytochrome bj reductase and cytochrome bs... 

Methemoglobin reductase deficiency Acetaminophen, anesthetics, topical, benzocaine, chloroquine, dapsone, nitrites, primaquine, sulfonamides Methemoglobinemia... 

Topical administration of lidocaine to the nasal mucosa occasionally causes severe methemoglobinemia in patients who have the heterozygous form of NADH methemoglobin reductase deficiency (63). 

Methemoglobinemia has been reported with benzocaine, Cetacaine (a mixture of benzocaine, butyl aminobenzo-ate, and tetracaine), cocaine, lidocaine, novocaine, and prUocaine. Acquired methemoglobinemia can result from exposure to chemicals that contain an aniline group, such as benzocaine and procaine, or to those that are transformed to metabolites that contain an aniline group, such as lidocaine and prilocaine. Toxic blood concentrations of local anesthetics, aberrant hemoglobin, and NADH-methemoglobin reductase deficiency are critical... 

Nitric oxide oxidizes hemoglobin to methemoglobin, two-thirds of which is reduced by nicotinamide adenine dinu-cleotide (NAD) methemoglobin reductase (1). Several ethnic groups, such as native Americans, have NAD methemoglobin reductase deficiency. There have been reports of methemoglobinemia after accidental overdosage of inhaled nitric oxide in native Americans and others (1). 

There may also be partial deficiency of methemoglobin reductase in neonates (1). In the Neonatal Inhaled Nitric Oxide Study the dose of inhaled nitric oxide had to be reduced in 11 of 114 patients (9.6%) because of raised methemoglobin. At doses of 1.25-80 ppm, methemoglobinemia is uncommon in one study only three of 471 (0.6%) patients discontinued therapy for this reason (17). 

Methemoglobinemia as an adverse effect of prilocaine (8) has been reported more often than with any other local anesthetic. It is caused by a metabolite and is a particular problem in neonates, who have an immature methemoglobin reductase system and residual fetal hemoglobin, increasing the risk of sjmptomatic methemoglobinemia. 

Specific therapy for toxic methemoglobinemia involves the administration of methylene blue, which acts as an electron transfer agent in the NADPH-methemoglobin reductase reaction and thereby increases the activity of this system several fold (Figure 34-3). Methylene blue and sulfhemo-globin cause spectral interference in the measurement of methemoglobin with some co-oximeters but not with the Evelyn-Malloy method. ... 

A condition described as "hereditary methemoglobinemia" may result from a genetic defect (Goldstein et al. 1969). The enzyme methemoglobin reductase is absent and persons are hypersensitive to any substances such as nitrite or aniline derivatives capable of producing methemoglobinemia. The trait is inherited as an autosomal recessive allele. Thus either sex may exhibit the trait which is ordinarily detected by the presence of cyanosis at birth. Such individuals would be extremely sensitive to the effects of nitrobenzene. 

The normal concentration of methemoglobin is 1.5% of total hemoglobin, although in congenital methemoglobinemia due to methemoglobin reductase deficiency this may increase to 10-20%. Methemoglobin... 

Hsieh, H.-S., and Jaffe, E. R., 1971, Electrophoretic and functional variants of NADH-methemoglobin reductase in hereditary methemoglobinemia, /. Clin. Invest. 50 196. 

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