Hypoglycemic encephalopathy

During the progression of hypoglycemic encephalopathy, as blood glucose falls below 2.5 mM (45 mg/dL), the brain attempts to use internal substrates such as glutamate and TCA cycle intermediates as fuels. Because the pool size of these substrates is quite small, they are quickly depleted. If blood glucose levels continue to fall below 1 mM (18 mg/dL), ATP levels become depleted. 

Yanagawa, Y, et al.. Diffusion-weighted MRI predicts prognosis in severe hypoglycemic encephalopathy. J Chn Neurosci, 2006. 13(6) p. 696-9. 

Behar KL, den Hollander JA, Petroff OAC, Hetherington HP, Prichard JW, Shulman RG. Effect of hypoglycemic encephalopathy upon amino acids, high-energy phosphates, and pHi in the rat brain in vivo Detection by sequential IH and 31P NMR spectroscopy. J Neuiochem 1985. 44 1045-1055... 

Frequent attacks of hypoglycemia can result in encephalopathy, and after withdrawal of the hypoglycemic drug cerebral injury can persist. It is not exceptional for prolonged hypoglycemic coma to end fatally (43,44). In 494 cases of severe hypoglycemia, 10% of the patients died and 9% had permanent sequelae (45). 

D. Toxicity Drowsiness and paresthesias are commonly reported after oral therapy. Cross allergenicity between these and all other sulfonamide derivatives (other sulfonamide diuretics, hypoglycemic agents, antibacterial sulfonamides) is uncommon but does occur. Alkalinization of the urine by these drugs may cause precipitation of calcium salts and formation of renal stones. Renal potassium wasting may be marked. Patients with hepatic impairment may develop hepatic encephalopathy because of increased ammonia reabsorption. 

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