Intoxication with methemoglobinizing substances

Aromatic amines

• Aniline, toluidine - liquids.
• Benzidine , 2-naphthylamine - pinkish powder substance.

Professional exposure

• Production of dyes (textiles, paper, leather), plastics, rubber, pesticides.

Etiopathogenesis

• Fat-soluble substances - they are well absorbed by the skin ,
• They are metabolized into hydroxylamines, which change hemoglobin into methemoglobin , create VR in erythrocytes and give rise to so-called Heinz bodies in erythrocytes (precipitated hemoglobin with cytoskeletal proteins),
• Erythrocytes are more fragile, hemolysis , hemoglobinuria and subsequent kidney damage may occur .
• They are removed by acetylation (people we refer to as so-called slow acetylators are at risk of bladder cancer ).

Aniline (its metabolite phenylhydroxylamine) has the strongest methemoglobinizing effect → functional anemia occurs , the curve shifts to the left, and tissue hypoxia increases . Therapy uses alternative ways of reducing methemoglobin by the enzyme NADPH methemoglobin reductase - it needs methylene blue (a redox substance) as a cofactor.

Clinical picture

Acute – lower exposure – CNS excitation (so-called aniline spike);

• Then the manifestations depend on the degree of metHbemia ,
  • 10–30% cyanosis , tachycardia , fatigue,
  • 30-50% weakness, shortness of breath, headache,
  • 50-70% impaired consciousness and death,
• The blood taken is dark brown to black in color (striking plum-blue cyanosis).

Chronic - polyglobulia due to chronic hypoxia.

Therapy

Antidote - methylene blue .

Indication

• Symptoms of hypoxemia ( dyspnea , confusion, chest pain),
• Methemoglobinemia at 25%,
• Initial dose – 1–2 mg/kg iv,
• Risks - people with a defect of G6P-dehydrogenase (they do not create NADPH) - it does not work and, moreover, it accumulates and can aggravate methemoglobinemia and cause hemolysis.

Toluidine blue - works by the same mechanism, paradoxically, cyanosis deepens after administration (given by the color of the antidote) ascorbic acid - works weaker and slower.

Aromatic nitro compounds

• They have the NO 2 group , e.g. nitrobenzene, TNT, trinitrophenol (picric acid),
• Professional exposure – production of aniline, dyes, explosives,
• Etiopathogenesis - they are well absorbed by the skin, by a similar mechanism to the previous ones, they cause methemoglobinemia. In addition, TNT causes massive necrosis and yellow atrophy of the liver with a lethal end, or cataract.

Nitroglycerin

• Oily liquid, easily explosive,
• Application – manufacture of explosives, pharmacology,
• They are easily absorbed through the skin, after absorption they are hydrolyzed into inorganic compounds and cause vasodilation,
• After 2-4 days of professional exposure, tolerance develops (thanks to compensatory sympathetic mechanisms) → angina pectoris may occur after exposure is interrupted ,
• After high doses, methemoglobinemia, of mild degree, without Heinz bodies, may occur.
• Acute intoxication - headaches (caused by vasodilatation of CNS vessels), "powder headache" in the occiput, restlessness, depression , sleep disorders, paleness of sweating, drop in pressure, shock,
• High doses – methemoglobinaemia, shortness of breath, unconsciousness,
• Professional exposure - typically the so-called "Monday sickness" - always after a weekend break, compensation sets in during the week, symptoms disappear...,
• Chronic intoxication - angina pectoris and sudden death, paradoxically on days off from work (after interruption of exposure), pseudoneurasthenic symptoms are also described.

Therapy

• Angina from habit - we will remove nitrates,
• Acute hypotension is difficult to influence therapeutically - anti-shock position, IV fluids, possibly dopamine , norepinephrine .

Nitrites

Synonym: nitrites, -NO 2 ,

• Sodium nitrite – a yellowish solid substance soluble in water,
• It was also used as a methemoglobinizing substance in cyanide poisoning,
• Additive for smoking meat, for cigarette papers, for fuel,
• Lethal dose after – 4g .

Nitrates

Synonym: nitrates, -NO 3 ,

• In order to cause metHbemia, they must be reduced to nitrites by flora in the intestine,
• They are dangerous for infants (they have bacteria in the GIT higher - due to less acidic stomach contents),
• As little as 10 mg/l can be dangerous for infants,
• Others, chlorates, drugs – primaquine (antimalarial), phenacetin (analgesic).

Links

related articles

• Intoxication by mercury and its compounds
• Intoxication by lead and its compounds

Source

• BENEŠ, Jiří. Studijní materiály [online]. [cit. 24.02.2010]. <http://jirben.wz.cz>.