HYPOGLYCEMIC AGENTS Rama B Rao M D Bellevue
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 Glucose Pyruvate Kreb’s Cycle Oxidative Phosphorylation ATP
MUSCLE CELLS Glycogen P EPINEPHRINE GLUCAGON I Glucose Pyruvate Kreb’s Oxidative Phosphorylation ATP
MUSCLE CELLS FFA P I KETONES Glucose Pyruvate Kreb’s Oxidative Phosphorylation ATP
BRAIN Glycogen KETONES Pyruvate Glucose P Krebs Oxidative Phosphorylation ATP
HYPOGLYCEMIA • • • Hunger/Anxiety Focal neurological deficits Confusion Seizures Coma Hypothermia
BRAIN: Anterior Pituitary ATP P Glucose GH EXCITATORY NT Adrenal medulla Catecholamines
Other Manifestations • Tachycardia • Tremor • Diaphoresis
ALPHA CELL OF PANCREAS Decreased Glucose GLUCAGON Catecholamines, Amino acids
MUSCLE CELLS Glycogen P EPINEPHRINE GLUCAGON I Glucose Pyruvate Kreb’s Oxidative Phosphorylation ATP
LIVER CELL I Glycogen Storage EPINEPHRINE GLUCAGON P Glucose Pyruvate Kreb’s Cycle Oxidative Phosphorylation ATP
PANCREAS: BETA ISLET CELL Insulin ++ Ca 2+ +++++ MEMBRANE DEPOLARIZATION
PANCREAS: BETA ISLET CELL Insulin K+ ATP +++++ Ca 2+ Sulfonylurea, Meglitinides* *Repaglinide
SULFONYLUREAS • Risk of hypoglycemia – Fasting – Elderly: variable data – Chronic renal failure
SULFONYLUREA INDUCED HYPOGLYEMIA • • Administration of glucose for acute correction Decontamination Nutrition, IV access Admission
SULFONYLUREAS • • Monitor potassium, phosphate Urinary alkalinization for chlorpropamide Octreotide for refractory hypoglycemia Observation for at least 12 hours after last dose octreotide
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
PANCREAS: BETA ISLET CELL Insulin K+ ATP ----- Ca 2+ DIAZOXIDE
PANCREAS: BETA ISLET CELL Insulin G Ca 2+ OCTREOTIDE
SUFONYLUREAS: Other Effects • Inhibition of aldehyde dehydrogenase • SIADH
INSULIN • Oral exposure is benign • Parenteral Exposures – Unpredictable in overdose – May be dependent upon quantity injection – Formulation • Treatment: nutrition, supplemental glucose infusion
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
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
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
MUSCLE CELL Glycogen P I Glucose Pyruvate METFORMIN Kreb’s Oxidative Phosphorylation ATP
LIVER CELL Glycogen P Pyruvate Oxidative Phosphorylation METFORMIN ATP
OTHER AGENTS AFFECTING CARBOHYDRATE METABOLISM • • • Ethanol Beta adrenergic antagonists Unripened ackee fruit Valproic acid Salicylates Pentamidine • Quinidine • Disopyramide
LIVER CELL Glycogen Pyruvate Glucose Acetate NADH+H+ Oxidative Phosphorylation ATP ETHANOL NAD+ Lactate
ALPHA CELL OF PANCREAS Decreased Glucose GLUCAGON BETA ADRENERGIC ANTAGONISTS Catecholamines, Amino acids
LIVER CELL Glycogen P Pyruvate Oxidative Phosphorylation ACKEE ATP
LIVER FFA ACKEE VALPROIC ACID P I KETONES Glucose Pyruvate Kreb’s Oxidative Phosphorylation ATP
LIVER P I Glucose Pyruvate Alanine Kreb’s SALICYLATES Oxidative Phosphorylation ATP
PANCREAS: BETA ISLET CELL Insulin ++ Ca 2+ PENTAMIDINE ALLOXAN STREPTOZOCIN +++ Membrane depolarization
BRAIN Pyruvate P THIAMINE Acetyl Co A GLUCOSE Kreb’s Oxidative Phosphorylation ATP
MUSCLE CELL I Glycogen Storage P I Glucose Pyruvate Kreb’s Cycle Oxidative Phosphorylation ATP
MUSCLE CELLS Glycogen P EPINEPHRINE GLUCAGON I Glucose Pyruvate Kreb’s Oxidative Phosphorylation ATP
MUSCLE CELLS FFA P I KETONES Glucose Pyruvate Kreb’s Oxidative Phosphorylation ATP
BRAIN Glycogen KETONES Pyruvate Glucose P Krebs Oxidative Phosphorylation ATP
LIVER CELL I Glycogen Storage EPINEPHRINE GLUCAGON P Glucose Pyruvate Kreb’s Cycle Oxidative Phosphorylation ATP
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