Methaemoglobinaemia

Nitrate is not a new problem. Excessive concentrations were recorded in many domestic wells in a survey conducted 100 years ago. What is new is the public concern about nitrate. This arises from two medical conditions that have been linked to nitrate methaemoglobinaemia ( bine-baby syndrome ) in infants, and stomach cancer in adults. Both are serious conditions, so we need to examine possible links carefully, but we need to note that these conditions are not caused by nitrate but by the nitrite to which it may be reduced. Nitrate itself is harmless and is most notable from a medical standpoint as a treatment for phosphatic kidney stones. 

Is there a Safe Limit for Nitratel The two previous sections show that any safe limit for nitrate needs to be related to methaemoglobinaemia rather than... 

Fig.19.3,19.4) Contact allergy Contact urticaria Methaemoglobinaemia Hypotension... 

Primaquine should be administered cautiously to actually ill patients with any serious systemic disease characterized by a tendency to granulocytopenia such as rheumatoid arthritis or lupus erythematosus. The drug should be used with care in patients with glucose-6-phosphate dehydrogenase deficiency. Primaquine should be withdrawn if signs of haemolysis or methaemoglobinaemia occur and the blood... 

Co-trimoxazole is a folate antagonist and should be avoided in the first and the third trimesters of pregnancy. In the third trimester there is an increased risk of neonatal haemolysis and methaemoglobinaemia, whereas in the first trimester there is a teratogenic risk caused by the trimethoprim (folate antagonist) component. 

Prilocaine is a local anaesthetic of low toxicity, which should be avoided in severe or untreated hypertension, severe heart disease and in patients using drugs that may cause methaemoglobinaemia. Prilocaine may cause ocular toxicity, which has been reported with the use of the product in excessively high doses during ophthalmic procedures. 

Facchini V, Griffiths LA. 1981. The involvement of the gastro-intestinal microflora in nitro-compound-induced methaemoglobinaemia in rats and its relationship to nitrogoup reduction. Biochem Pharmacol 30 931-935. 

Adverse effects include nausea, vomiting, nervousness, palpitation, sweating, headache, disorientation, methaemoglobinaemia. 

Adverse effects include flushing, headache, dizziness, methaemoglobinaemia and drug rash. 

Adverse effects include nausea, vomiting, weakness, abdominal pain and methaemoglobinaemia. Haemolytic anaemia in patients with G-6-PD deficiency. Passage of dark urine is indication of haemolysis. In larger dose it can cause leucopenia. 

Adverse effects include haemolysis which is most common and dose related. Patients with G-6-PD deficiency are more susceptible. Nausea, vomiting, anorexia, headache, methaemoglobinaemia, drug fever, allergic skin reactions, insorrmia and paresthesia. Rarely hepatitis and agranulocytosis. 

Coleman, M.D. Coleman, N.A. (1996) Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf, 14, 394 05... 

In humans, 4-chloro-ort/2o-toluidine induces acute toxicity in the urinary bladder and causes methaemoglobinaemia. In rodents, 4-chloro-ort/zo-toluidine and/or its metabolites bind to macromolecules in liver cells. 

These are generally metabolised in the hepatic endoplasmic reticulum, the initial reaction being N-dealkylation, with subsequent hydrolysis. An exception to this is prilocaine, where the initial step is hydrolysis, forming o-toluidine. This is further metabolised to 4- and 6-hydro toluidine. The latter is believed to be responsible for the methaemoglobinaemia which may follow high doses. The amidelinked local anaesthetics are extensively protein-bound (between 55% and 95%) particularly to ol-acid glycoprotein. 

Several cases of serious and even fatal intoxication after dermal application of resorcinol have been described. Methaemoglobinaemia, haemolysis and convulsions have often been noted (Cunningham, 1956 Lundell Nordman, 1973 Bontemps et al., 1995). Resorcinol is a rare cause of allergic contact dermatitis (Vilaplana et al., 1991 Pecegueiro, 1992 Serrano et al., 1992 Massone et al., 1993) and may also induce generalized eczema, urticaria and angioneurotic oedema (Barbaud et al., 1996). 

With modem methods of intensive farming in which nitrate-based fertilisers are employed, there has been a noticeable increase in nitrate levels from aquifers lying beneath agricultural land. The recommended limit for nitrate has been given as 50 mg/1 by the World Health Organization (WHO). The principal health risk of nitrates involves a condition seen in infants known as methaemoglobinaemia. 

Methaemoglobinaemia (and the effects induced by oxygen deficiency) disturbed heart function, liver and kidney trouble and a dysfunction of the whole vascular system. 

Tetranitromethane is highly toxic. Kiese [48] found that 25 mg/per kg of body weight of tetranitromethane slowly injected intravenously caused transitory methaemoglobinaemia, as well as lung oedema and damage to the liver, kidney and central nervous system. Tetranitromethane injected quickly caused necrosis around the puncture which could be fatal. 

High nitrate concentrations can cause methaemoglobinaemia (blue-baby syndrome) in bottle-fed infants. This condition is also associated with the simultaneous presence of bacterial contamination. The primary approach to managing nitrate contamination is prevention, particularly for rural wells, which are the major problem with regard to methaemoglobinaemia. In particular, protection of wells from runoff from fields and siting of manure stores, pit latrines and septic tanks will help to prevent contamination with nitrate and microbial pathogens. 

There has long been concern expressed over the presence of nitrate in drinking water at concentrations exceeding the EC guideline of 50 mg L because of the risk of methaemoglobinaemia (blue baby syndrome). Here,... 

PRILOCAINE SULPHONAMIDES Risk of methaemoglobinaemia a case report of methaemoglobinaemia with topical prilocaine in a patient taking sulphonamides Additive effect Avoid co-administration... 

Sodium and potassium chlorates are popular weedkillers which are highly toxic after oral ingestion. Cyanosis and methaemoglobinaemia are common features of poisoning with these substances. A test for oxidising agents in stomach contents is given on p. 5. 

Toxicity. Methaemoglobinaemia and acute renal failure have been reported after overdoses. 

Toxicity. Toxic effects are usually associated with plasma concentrations greater than 5 pg/ml. 4-Hydroxy-2-methylaniline is thought to be responsible for the methaemoglobinaemia which may occur after large doses. 

Marrs, T.C., Bright, J.E. (1986). Kinetics of methaemo-globin production (I). Kinetics of methaemoglobinaemia induced by cyanide antidotes, p-aminopropiophenone, p-hydroxyl aminopropiophenone or p-dimethylaminophenol after intravenous administration. Hum. Toxicol. 6 139 5. 

Coleman MD, Coleman NA. Drug-induced methaemoglobinaemia — treatment issues. Drug Saf 1996 14 394-405. 

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