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