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

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

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

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

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

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

9. Other Manifestations Tachycardia Tremor Diaphoresis

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

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

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

13. Ca 2+ PANCREAS: BETA ISLET CELL Insulin ++ +++++ MEMBRANE DEPOLARIZATION

14. K+K+ ATP Ca 2+ PANCREAS: BETA ISLET CELL Insulin 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. K+K+ ATP Ca 2+ PANCREAS: BETA ISLET CELL Insulin DIAZOXIDE - - - - -- - -

20. Ca 2+ PANCREAS: BETA ISLET CELL Insulin OCTREOTIDE G

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 –D 50 W 1 gram/kg Children –D 25 W 0.5-1 gram/kg –D 10 W 0.5-1 gram/kg in neonates Infusion of D 10 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. Glycogen Glucose MUSCLE CELL P Pyruvate I Kreb’s ATP METFORMIN Oxidative Phosphorylation

27. Glycogen LIVER CELL P Pyruvate ATP METFORMIN Phosphorylation Oxidative

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

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

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

31. Glycogen LIVER CELL P Pyruvate ATP Phosphorylation Oxidative ACKEE

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

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

34. Ca 2+ PANCREAS: BETA ISLET CELL Insulin ++ +++ Membrane depolarization PENTAMIDINE ALLOXAN STREPTOZOCIN

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

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

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

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

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

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