A reducing substance is needed to convert the methaemoglobin (ferric iron) back to oxyhaemo-globin (ferrous iron) whenever enough has formed seriously to impair the oxygen-carrying capacity of the blood. Ascorbic acid is nontoxic (it acts by direct reduction) but is less effective than methylene blue (methylthioninium chloride). Both can be given orally, i.v. or i.m. Excessive doses of methylene blue can cause methaemoglobinaemia (by stimulating NADPH-dependent enzymes).
Methaemoglobinaemia may be induced by oxidising drugs: sulphonamides, nitrites, nitrates (may also occur in drinking water), primaquine, -caine local anaesthetics, dapsone, nitrofurantoin, nitroprusside, vitamin K analogues, chlorates, aniline and nitrobenzene. In the rare instance of there being urgency, methylene blue 1 mg/kg slowly i.v. benefits within 30 min. (Ascorbic acid competes directly with the chemical cause but is inadequate in severe cases, which are the only ones that need treatment.)
In the congenital form, oral methylene blue with or without ascorbic acid gives benefit in days to weeks.
Methylene blue turns the urine blue and high concentrations can irritate the urinary tract, so that fluid intake should be high when big doses are used.
Sulphaemoglobinaemia cannot be treated by drugs. It can be caused by sulphonamides, nitrites or nitrates.
The agents are closely interrelated and will be discussed together.
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