156 - Hypoglycemic Agent Overdose

The primary metabolic substrate for the central nervous system (CNS) is glucose. Usual sources of glucose are diet, endogenous production (through gluconeogenesis), and storage (through glycogenolysis). Serum glucose concentrations are relatively tightly controlled by physiologic mechanisms. After dietary sources of glucose are completely used, glycogenolysis is the major physiologic mechanism for maintaining euglycemia. Typically, an adult has enough glycogen to last approximately 6 to 8 hours. When glycogen stores are depleted, gluconeogenesis, which is fueled by amino acids from muscle, takes over. The CNS cannot make or store glucose, and it relies on the previously mentioned mechanisms to maintain normal metabolic activity during fasting periods. As glucose use exceeds glucose production and serum glucose concentrations decrease, various counterregulatory pathways are activated. Counterregulatory pathways triggered at the glycemic threshold are increases in glucagon, epinephrine, growth hormone, and cortisol. Glycemic thresholds are fairly reproducible in research studies on healthy subjects, but these thresholds can vary significantly among patients with both type 1 and type 2 DM. These thresholds also depend on other factors, such as tightness of glucose regulation, the presence of chronic hyperglycemia, and recent episodes of hypoglycemia. Hypoglycemic agents induce hypoglycemia by various mechanisms. Insulins cause rapid transport of amino acids and glucose intracellularly. Sulfonylureas stimulate insulin secretion by binding to specific membrane receptors on the pancreatic beta-islet cell. These drugs also benefit glucose homeostasis by decreasing hepatic glucose production and improving insulin sensitivity at the receptor and postreceptor levels. Other drugs may induce hypoglycemia by inhibition of gluconeogenesis, glycogenolysis, counterregulatory hormones, or other unknown mechanisms. Ethanol, a toxin commonly encountered in the ED, inhibits gluconeogenesis by depleting nicotinamide adenine dinucleotide and also inhibits the effects of cortisol, growth hormone, and epinephrine.