Pharmacology Compiled By: Joshua James Diao, MAN, RN I.

Drugs Used in Diabetes

Diabetes Mellitus (3Ps: Polyuria, Polyphagia, Polydypsia) Type 1 - Early Onset - Loss on Pancreatic Beta Cells (Absolute Dependence on Insulin) - Ketoacidosis Prone Type 2 -

Usually adult onset Decreased response to insulin Non-Ketoacidosis Prone Severe Consequence: Hyperosmolar Hyperglycemic Coma

[Insulins] Insulin Forms Form Lispro* Regular* Glargine Route: Subcutaneous Onset 15-30 Minutes 30 Minutes 1 Hour 1 Hour Peak 1 2 Hours 2-4 Hours No Peak Duration 3-4 Hours 5-7 Hours > 24 Hours

* Only forms that can be used intravenously; peak action in 2-4 minutes. (Solutions) * Others; (Suspension) Clinical Correlate: Diabetic Ketoacidosis - Symptoms: * Polyuria * Nausea * Fatigue * Dehydration * Kussmaul Breathing * Fruity Breath => Acetone - Treatment: * Regular Insulin + Glucose (Avoid Fatal Hypoglycemia) * Fluids and Electrolyte Replacement (Avoid Hypokalemia Insulin Drives Potassium Into Muscle Cells) Ketone Bodies: Beta Hydroxybutyrate => Yields (1) NADH, (2) Acetyl CoA Acetoacetate => Yields (2) Acetyl CoA

Pharmacology Compiled By: Joshua James Diao, MAN, RN [Oral Hypoglycemic Agents] A. Sulfonylureas - Block Potassium Channels => Opening of Calcium Channels (Depolarization) => Calcium Influx Releases Insulin

Effect: * Increased Insulin Release * Decreased Glucagon Release * Increased Insulin Receptor Sensitivity Effects of Increased Insulin: - Decrease in Glucagon release from pancreatic alpha cells * Continued use of sulfonylureas increases tissue responses to insulin Drug Interactions: 1st Generation - Acetohexamide (Active Metabolites) - Tolbutamide (No Worry for Kidney) - Chlorpropamide ( Disulfiram-Like Effect / SIADH) 2nd Generation - Glipizide (Decrease Dose in Hepatic Dysfunction) - Glyburide (Active Metabolite, Decrease Dose in Renal Dysfunction) Side Effects: *Highly Protein Bound - Hypoglycemia (Fasting) => Small Frequent Meals, Worse Time: Early Morning - Weight Gain (Increased Fatty Acid Synthesis and Storage) - Drug Hypersensitivity - Drug Interactions (1st Generation) => Increased Hypoglycemia *cimetidine *insulin *salicylates=> High Protein Binding Displaces Bound Sulfonylureas *sulfonamides=> High Protein Binding - Displaces Bound Sulfonylureas B. Metformin Euglycemic Drug => NO HYPOGLYCEMIA - decreased postprandial glucose levels, but does not cause hypoglycemia or weight gain. Mechanism: increased tissue sensitivity to insulin and/or decreased hepatic gluconeogenesis Use: Monotherapy or Combinations (synergistic with sulfonylureas) Side-Effects:

Pharmacology Compiled By: Joshua James Diao, MAN, RN * Lactic Acidosis (RARE) => Increased Glycolysis => Build-Up of Lactate * GI Distress (Common)

C. Acarbose - No Hypoglycemia Mechanism: Inhibits alpha-glucosidase in brush borders of small intestines > decreased absorption of carbohydrates > decreased post-prandial glucose > decreased demand for insulin: Side-Effects: *GI Discomfort *Flatulence *Diarrhea *Potential Hepatotoxicity D. Thiazolidinediones: Pioglitazone & Rosiglitazone Mechanisms: bind to nuclear PPARs involved in transcription of insulin-responsive genes => sensitization of tissues to insulin, plus decreased hepatic gluconeogenesis and triglycerides and increased insulin receptor numbers. Side-Effects: *Less Hypoglycemia than Sulfonylureas *Weight Gain *Edema