HYPOGLYCEMIC AGENTS
description
Transcript of HYPOGLYCEMIC AGENTS
HYPOGLYCEMICAGENTS
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
Glycogen
Glucose
MUSCLE CELL
Storage
P
Pyruvate
Kreb’s Oxidative ATPPhosphorylation
Cycle
I
I
Glucose
MUSCLE CELLS
P
Pyruvate
I
Kreb’s ATP
Glycogen
EPINEPHRINEGLUCAGON
OxidativePhosphorylation
Glucose
MUSCLE CELLS
P
Pyruvate
I
Kreb’s ATP
KETONES
FFA
PhosphorylationOxidative
P
Glycogen
Glucose
BRAIN
Pyruvate
KrebsOxidativePhosphorylation
ATP
KETONES
HYPOGLYCEMIA
• Hunger/Anxiety
• Focal neurological deficits
• Confusion
• Seizures
• Coma
• Hypothermia
P
Glucose
BRAIN: Anterior Pituitary
ATP
GHEXCITATORY NT
Adrenal medullaCatecholamines
Other Manifestations
• Tachycardia
• Tremor
• Diaphoresis
ALPHA CELL OF PANCREAS
GLUCAGON
DecreasedGlucose
Catecholamines, Amino acids
Glucose
MUSCLE CELLS
P
Pyruvate
I
Kreb’s ATP
Glycogen
EPINEPHRINEGLUCAGON
OxidativePhosphorylation
Glycogen
Glucose
LIVER CELL
Storage
I
P
Pyruvate
Kreb’s ATP
EPINEPHRINEGLUCAGON
Oxidative
CyclePhosphorylation
Ca2+
PANCREAS: BETA ISLET CELL
Insulin
++ +++++
MEMBRANE DEPOLARIZATION
K+
ATP
Ca2+
PANCREAS: BETA ISLET CELL
Insulin
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
K+
ATP
Ca2+
PANCREAS: BETA ISLET CELL
Insulin
DIAZOXIDE
- - - - -- - -
Ca2+
PANCREAS: BETA ISLET CELL
Insulin
OCTREOTIDE
G
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– 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
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
Glycogen
Glucose
MUSCLE CELL
P
Pyruvate
I
Kreb’s ATPMETFORMIN Oxidative
Phosphorylation
Glycogen
LIVER CELL
P
Pyruvate
ATP
METFORMIN
PhosphorylationOxidative
OTHER AGENTS AFFECTING CARBOHYDRATE METABOLISM
• Ethanol
• Beta adrenergic antagonists
• Unripened ackee fruit
• Valproic acid
• Salicylates
• Pentamidine
• Quinidine
• Disopyramide
Glycogen
Glucose
LIVER CELL
Pyruvate
Oxidative
ATP
Lactate
Phosphorylation
NAD+
NADH+H+
ETHANOL
Acetate
ALPHA CELL OF PANCREAS
GLUCAGON
DecreasedGlucose
Catecholamines, Amino acids
BETA ADRENERGICANTAGONISTS
Glycogen
LIVER CELL
P
Pyruvate
ATPPhosphorylationOxidative
ACKEE
Glucose
LIVER
P
Pyruvate
I
Kreb’s ATP
KETONES
FFA
PhosphorylationOxidative
ACKEEVALPROIC ACID
Glucose
LIVER
P
Pyruvate
I
Kreb’s ATP
PhosphorylationOxidative
Alanine
SALICYLATES
Ca2+
PANCREAS: BETA ISLET CELL
Insulin
++ +++
Membrane depolarization
PENTAMIDINEALLOXAN
STREPTOZOCIN
P
BRAIN
Pyruvate
Kreb’s
OxidativePhosphorylation
ATP
Acetyl Co A
THIAMINE
GLUCOSE
Glycogen
Glucose
MUSCLE CELL
Storage
P
Pyruvate
Kreb’s Oxidative ATPPhosphorylation
Cycle
I
I
Glucose
MUSCLE CELLS
P
Pyruvate
I
Kreb’s ATP
Glycogen
EPINEPHRINEGLUCAGON
OxidativePhosphorylation
Glucose
MUSCLE CELLS
P
Pyruvate
I
Kreb’s ATP
KETONES
FFA
PhosphorylationOxidative
P
Glycogen
Glucose
BRAIN
Pyruvate
KrebsOxidativePhosphorylation
ATP
KETONES
Glycogen
Glucose
LIVER CELL
Storage
I
P
Pyruvate
Kreb’s ATP
EPINEPHRINEGLUCAGON
Oxidative
CyclePhosphorylation