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HYPOGLYCEMIC AGENTS

HYPOGLYCEMIC AGENTS. Rama B. Rao, M.D. Bellevue Hospital Center/NYUMC New York, N.Y. Glycemic Control Agents. Insulin Sulfonylureas Meglitinides: Repaglinide Biguanides: Metformin Thiazolidinediones: Pioglitazone  Glucosidase inhibitors. MUSCLE CELL. I. Glycogen. Storage. P. I.

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HYPOGLYCEMIC AGENTS

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  1. HYPOGLYCEMICAGENTS Rama B. Rao, M.D. Bellevue Hospital Center/NYUMC New York, N.Y.

  2. Glycemic Control Agents • Insulin • Sulfonylureas • Meglitinides: Repaglinide • Biguanides: Metformin • Thiazolidinediones: Pioglitazone •  Glucosidase inhibitors

  3. MUSCLE CELL I Glycogen Storage P I Glucose Pyruvate Oxidative ATP Kreb’s Phosphorylation Cycle

  4. MUSCLE CELLS Glycogen P I EPINEPHRINE GLUCAGON Glucose Pyruvate Oxidative ATP Kreb’s Phosphorylation

  5. MUSCLE CELLS FFA P I KETONES Glucose Pyruvate ATP Oxidative Kreb’s Phosphorylation

  6. BRAIN Glycogen KETONES Pyruvate P Glucose Oxidative Phosphorylation Krebs ATP

  7. HYPOGLYCEMIA • Hunger/Anxiety • Focal neurological deficits • Confusion • Seizures • Coma • Hypothermia

  8. BRAIN: Anterior Pituitary ATP P Glucose GH EXCITATORY NT Adrenal medulla Catecholamines

  9. Other Manifestations • Tachycardia • Tremor • Diaphoresis

  10. ALPHA CELL OF PANCREAS Decreased Glucose GLUCAGON Catecholamines, Amino acids

  11. MUSCLE CELLS Glycogen P I EPINEPHRINE GLUCAGON Glucose Pyruvate Oxidative ATP Kreb’s Phosphorylation

  12. LIVER CELL I Glycogen Storage EPINEPHRINE P GLUCAGON Glucose Pyruvate ATP Oxidative Kreb’s Phosphorylation Cycle

  13. PANCREAS: BETA ISLET CELL Insulin +++++ ++ Ca2+ MEMBRANE DEPOLARIZATION

  14. PANCREAS: BETA ISLET CELL Insulin K+ ATP +++++ Ca2+ Sulfonylurea, Meglitinides* *Repaglinide

  15. SULFONYLUREAS • Risk of hypoglycemia • Fasting • Elderly: variable data • Chronic renal failure

  16. SULFONYLUREA INDUCED HYPOGLYEMIA • Administration of glucose for acute correction • Decontamination • Nutrition, IV access • Admission

  17. SULFONYLUREAS • Monitor potassium, phosphate • Urinary alkalinization for chlorpropamide • Octreotide for refractory hypoglycemia • Observation for at least 12 hours after last dose octreotide

  18. Octreotide Dosing • Adults: 50 g subcutaneously every 6 hours • Children: 4-5 g/kg/day subcutaneously divided every 6 hours, with maximum not exceeding the adult dose

  19. PANCREAS: BETA ISLET CELL Insulin K+ ATP - - - - - - - - Ca2+ DIAZOXIDE

  20. PANCREAS: BETA ISLET CELL Insulin G Ca2+ OCTREOTIDE

  21. SUFONYLUREAS: Other Effects • Inhibition of aldehyde dehydrogenase • SIADH

  22. INSULIN • Oral exposure is benign • Parenteral Exposures • Unpredictable in overdose • May be dependent upon quantity injection • Formulation • Treatment: nutrition, supplemental glucose infusion

  23. HYPOGLYCEMICS: MANAGEMENT • Identify and treat hypoglycemia • Admission especially if brought to coma or seizure • Nutrition • Consider enteral infusion of feeds via NG Tube • Monitor electrolytes

  24. GLUCOSE ADMINISTRATION • Adults • D50W 1 gram/kg • Children • D25W 0.5-1 gram/kg • D10 W 0.5-1 gram/kg in neonates • Infusion of D10 W at a total of 1 gram/kg/hr • Monitor potassium

  25. METFORMIN • Rarely causes true hypoglycemia • Adverse reaction • Lactic acidosis only in patients with renal insufficiency or shock states. • Treatment of lactic acidosis: hemodialysis • Caveat: Co-ingested substances

  26. MUSCLE CELL Glycogen P I Glucose Pyruvate METFORMIN Oxidative ATP Phosphorylation Kreb’s

  27. LIVER CELL Glycogen P Pyruvate Oxidative ATP Phosphorylation METFORMIN

  28. OTHER AGENTS AFFECTING CARBOHYDRATE METABOLISM • Ethanol • Beta adrenergic antagonists • Unripened ackee fruit • Valproic acid • Salicylates • Pentamidine • Quinidine • Disopyramide

  29. LIVER CELL Glycogen Pyruvate Glucose Oxidative Phosphorylation NADH+H+ Acetate ATP ETHANOL NAD+ Lactate

  30. ALPHA CELL OF PANCREAS Decreased Glucose GLUCAGON BETA ADRENERGIC ANTAGONISTS Catecholamines, Amino acids

  31. LIVER CELL Glycogen P Pyruvate Oxidative ATP Phosphorylation ACKEE

  32. LIVER FFA ACKEE VALPROIC ACID P I KETONES Glucose Pyruvate ATP Oxidative Kreb’s Phosphorylation

  33. LIVER P I Glucose Pyruvate Alanine ATP Oxidative Kreb’s Phosphorylation SALICYLATES

  34. PANCREAS: BETA ISLET CELL Insulin PENTAMIDINE ALLOXAN STREPTOZOCIN +++ ++ Ca2+ Membrane depolarization

  35. BRAIN Pyruvate P THIAMINE Acetyl Co A Oxidative Phosphorylation GLUCOSE Kreb’s ATP

  36. MUSCLE CELL I Glycogen Storage P I Glucose Pyruvate Oxidative ATP Kreb’s Phosphorylation Cycle

  37. MUSCLE CELLS Glycogen P I EPINEPHRINE GLUCAGON Glucose Pyruvate Oxidative ATP Kreb’s Phosphorylation

  38. MUSCLE CELLS FFA P I KETONES Glucose Pyruvate ATP Oxidative Kreb’s Phosphorylation

  39. BRAIN Glycogen KETONES Pyruvate P Glucose Oxidative Phosphorylation Krebs ATP

  40. LIVER CELL I Glycogen Storage EPINEPHRINE P GLUCAGON Glucose Pyruvate ATP Oxidative Kreb’s Phosphorylation Cycle

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