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).

related articles

 * Intoxication by mercury and its compounds
 * Intoxication by lead and its compounds