Toxicity methemoglobinemia

NO activates soluble guanylyl cyclase to elevate cGMP levels in vascular smooth muscle Vasodilator relaxes other smooth muscle inhalation of NO leads to increased blood flow to parts of the lung exposed to NO and decreased pulmonary vascular resistance Hypoxic respiratory failure and pulmonary hypertension Inhaled gas Toxicity Methemoglobinemia... 

Fisher MA, Henry D, Gillam L, Chen C. Toxic methemoglobinemia a rare but serious comphcation of transesophageal echocardiography Can J Cardiol 1998 14(9) 1157-60. 

Stoiber TR. Toxic Methemoglobinemia comphcating transesophageal echocardiography. Echocardiography 1999 16(4) 383-5. 

In eight episodes of toxic methemoglobinemia in seven premature infants after the combination of caudal anesthesia (prilocaine 5.4—6.7 mg/kg) and Emla cream (prilocaine 12.5 mg) for herniotomy, the highest methe-moglobin concentration 5.5 hours after anesthesia was 31% (86). All the infants were sjmptomatic, with mottled skin, pallor, cyanosis, and poor peripheral perfusion. The most severe symptoms occurred at 3-8 hours and disappeared within 10-20 hours. The authors stressed the importance of recognizing the poor tolerance of premature infants to methemoglobinemia and that whereas topical prilocaine is relatively safe, caudal administration is not. 

An acquired (toxic) methemoglobinemia may be caused by a number of drugs and chemicals (Table 34-5). 

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. ... 

Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. 

Hematologic Ibuprofen can be associated with toxic methemoglobinemia [26 ]. 

Toxic methemoglobinemia occurred in a 7-month-old boy, who developed cyanosis 8 hours after receiving ibuprofen 7.5 mg/kg. His methemoglobin concentration was 27% but fell after treatment with intravenous methylthioninium chloride (methylene blue). 

Bouziri A, Khaldi A, Menif K, Ben Jaballah N. Unusual cause of severe toxic methemoglobinemia in an infant a case report. Int J Emerg Med 2010 3 57-9. 

Inhalation is the chief route of worker exposure. Comparative data from acute or subchronic inhalation exposures with rats (98) indicate that nitromethane and nitroethane are the least toxic of the nitroparaffins by this route and do not induce methemoglobin formation. The nitropropanes are less well tolerated 2-nitropropane is more toxic than 1-nitropropane and is more likely to cause methemoglobinemia. 

The compound is an intermediate in several synthetic reactions and recently has found extensive use in experimental toxicity studies in animals. It has been shown to cause methemoglobinemia its metaboHsm in humans has been discussed (189,190). 

Prilocaine hydrochloride [1786-81-8] is also similar in profile to Hdocaine, although prilocaine has significantly less vasodilator activity. Prilocaine is the least toxic of the amino amide local anesthetics. However, its tendency to cause methemoglobinemia, especially in newborns, has eliminated its use in obstetric surgery. 

Although NOT is not usually thought of as a "toxic" chemical, it does cause several health problems including methemoglobinemia in infants (blue-baby syndrome) and may also be linked to stomach cancer. Agricultural runoff can lead to significant, potentially harmful, concentrations of NOT in ground or surface water. 

Smith RP, Gosselin RE. 1964. The influence of methemoglobinemia on the lethality of some toxic anions II. Sulfide. Toxicol Appl Pharmacol 6 584-592. 

The following factors have been suggested as alternatives to consider when presented with a potential case of exposure to carbon monoxide diabetic ketoacidosis, hypothyroidism and myxedema coma, labyrinthitis, and lactic acidosis toxic exposures resulting in methemoglobinemia ingestion of alcohols or narcotics and diseases that cause gastroenteritis, encephalitis, meningitis, and acute respiratory distress syndrome. 

As noted under Mechanisms of Toxicity (Section 4.2), nitrate and nitrite esters are vasodilators with resulting hypotension (Nickerson 1975). Therapeutic doses of nitroglycerin for relief of angina are associated with headaches of vascular origin. Both PGDN and the structurally related ethylene glycol dinitrate produce headaches in humans and methemoglobinemia and hypotension in rats (Andersen and Mehl 1979). 

Dinitrobenzene is an intermediate employed in chemical syntheses of a large number of compounds used in the dye, explosives and plastics industry. The compound is known to induce methemoglobinemia and to cause testicular toxicity with the Sertoli cell being the major target. Nitro reduction was observed in erythrocytes, in rat Sertoli-germ cell cocultures and in rat testicular subcellular fractions, and it was shown that 3-nitrosonitrobenzene was formed that was considerably more toxic. Testicular toxicity was enhanced when the intracellular thiol levels were reduced by pretreatment with diethylmaleate. In turn, pretreatment with cysteamine or ascorbate reduced the toxicity of 1,3-dinitrobenzene and 3-nitrosonitrobenzene. 

Polynitroaromatic compounds are used as explosives. They are toxic and might cause liver damage, methemoglobinemia and uncoupling of the oxidative phosphorylation process. Trace analyses of polynitroaromatic residues in groundwater, surface water, rainwater... 

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