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Pharmacology – Diabetes Drugs

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Pharmacology – Diabetes Drugs Drug Drug Class Mechanism of Action Indications Adverse Effects Contraindications Alpha Cells Glucagon Natural Pancreatic Hormone ------------------------------------------------------------------ Beta Cells ------------------------------------------------------------------ Pre-Pro-Insulin --> Pro-Inslin via PEPTIDASE Pro-Insulin --> Insulin + C Peptide ------------------------------------------------------------------ Uses Tyrosine Kinase Recptor STEPS: 1. Glucose Enters Beta Cells. 2. Glucose Indirectly Inhibits ATP-Sensitive K+ Channel 3. Depolarization oF the Membrane Triggers Ca2+ Mediated Overall Effect: Exocytosis oF Insulin Storing Granules. Favor Storage of Fuel 4. Binds + Activates Tyrosine Kinase Receptor --------------------------------------------- (Binds to Alpha, Phosphorylates Beta) Promotes K+ Uptake 5. Promoted Uptake oF Glucose by Up-Regulating GLUT-1 + GLUT-4 Inhibits Gluconeogenesis Promotes Cellular K+ Uptake: Insulin Natural Pancreatic Hormone 6. Alters the Phosphorlaytion State oF Key Metabolic Enzymes 7. Induces Transcription oF Several Genes Increases Glycolysis Hypokalemia (Inhibits Gluconeogenesis) Inhibits Glycogenolysis ------------------------------------------------------------------ Stimulates Glycogenesis Phases: Increases Synthesis oF Triglycerides First Phase: Increases Protein Synthesis Glucose Induced a BrieF Pulse oF Insulin Output (within 2 minutes) Second Phase: Delayed but More Sustained Insulin Release ------------------------------------------------------------------ Insulin Release Can be Caused By: 1. Glucose 2. GIT Hormones (GIP, CCK) (ORAL) 3. Adrenergic A2: Decreases Insulin Release (Pre-Dominant) 4. Adrenergic B2/Vagal: Increases Insulin Release (Less Dominant) Delta Cells Somatostatin Natural Pancreatic Hormone ------------------------------------------------------------------ Pancreatic F (PP) Cells Natural Pancreatic Hormone Polypeptide ------------------------------------------------------------------ Drug Drug Class Mechanism of Action Indications Adverse Effects Contraindications Bovine Insulin: Mad Cow Disease --> Removed From US Bovine Insulin BeeF Pancreas Same as Human Insulin Diabetes Mellitus Porcine Insulin: Allergy Concerns --> Removed From US Porcine Insulin Pork Pancreas Lipodystrophy Drug Reactions: Hypoglycemia: ----------------------------------------------------- Counter Regulatory Sympathetic Stimulation: B-Blockers: Sweating, Anxiety, Palpitation, Tremor Prolong Hypoglycemia by Inhibiting Neuroglucopenic Symptoms: Compensatory Mechanisms Deprivation oF Brain Glucose Also Masks Hypoglycemia Warning Signs Dizziness, Headache, Behavioral Changes, Visual (Sweating, Tremor) Disturbances, Fatigue, Weakness, Muscular Incoordination ----------------------------------------------------- Ultimately COMA Thiazides, Furosemide, Corticosteroids: ----------------------------------------------------------------------- Raise Blood Sugar Gestational Diabetes Advantages: Treatment for Hypoglycemia: Glucose Reduce Insulin EFFectiveness In Surgery/InFection Diminished Antibody: ----------------------------------------------------------------------- ----------------------------------------------------- --------------------------------------------------- Human Insulin Recombinant DNA Technology Less Change oF Insulin Resistance Somogyi Phenomenon: Alcohol: Cannot Be Ingested Less Allergic Reactions A contested explanation oF phenomena oF elevated blood Preciptates Hypoglycemia by Depleting Will be Digested by Less Lipodystrophy sugar in the morning. Hepatic Glycogen Proteolytic Enzymes A rebounding high blood sugar that is a response to low ----------------------------------------------------- blood sugar Insulin Resistance: ----------------------------------------------------------------------- Acute: Local Reactions (Lipodystrophy) Develops Rapidly Allergic Reactions (Protamine, Zinc) Short-Term Problem Local/Systemic Urticaria (Trauma, Stress, Etc.) Weight Gain (Insulin is Anabolic) Chronic: Edema Antibodies are Formed Against Hypokalemia Bovine/Porcine Insulin. Switch Patient to Human Insulin Diabetes Mellitus Insulin Lispro Onset Within 15 Minutes (Type I -- Sometimes Type II) Insulin Aspart Rapid-Acting Insulin Agonist Duration: <5 Hours Diabetic Ketoacidosis (Diabetic Coma) Same as Above Same as Above Insulin Glulisine Only Given SC Hyperosmolar (Non-Ketonic Hyperglycemic) Coma Diabetes Mellitus Regular Insulin Onset Within 30 Minutes (Type I -- Sometimes Type II) (Crystalline Zinc Short-Acting Insulin Agonist Duration: 5-8 Hours Diabetic Ketoacidosis (Diabetic Coma) Same as Above Same as Above Insulin/Soluble Insulin) Given SC, IV, IM Hyperosmolar Semilente Insulin (Non-Ketonic Hyperglycemic) Coma Diabetes Mellitus Neutral Protamine (Type I -- Sometimes Type II) Hagedorn Insulin Intermediate-Acting Insulin Duration: 24 Hours Diabetic Ketoacidosis (Diabetic Coma) Same as Above Same as Above (NPH Insulin) Agonist Hyperosmolar Lente Insulin (Non-Ketonic Hyperglycemic) Coma Utralente Diabetes Mellitus Insulin Glargine (Type I -- Sometimes Type II) Insulin Detemir Long (Slow)-Acting Insulin Agonist Duration: 30 Hours Diabetic Ketoacidosis (Diabetic Coma) Same as Above Same as Above Protamine-Zinc Hyperosmolar Insulin (Non-Ketonic Hyperglycemic) Coma Symptoms Management Management: -------------------------------------------- Regular Insulin IV (Bolus + InFusion) LiFe Threatening Medical Emergency After Patient Becomes Fully Generally Seen in Type I Diabetes Conscious: Causes: Maintainence with SC Injection InFection (Most Common) -------------------------------------------- Trauma IV Fluids: Stroke (To Correct Dehydration From Pancreatitis Osmotic Diuresis) StressFul Conditions Normal Saline (.9 NaCl) Diabetic Inadequate Doses oF Insulin Later, 5% Glucose in 1/2 N Saline Ketoacidosis -------------------------------------------------------------------- -------------------------------------------- Symptoms: KCl: Nausea/Vomiting Acidosis Causes Hypokalemia Abdominal Pain Insulin Therapy Causes Hypokalemia Kussmaul Breathing (Deep, Slow) -------------------------------------------- Change in Mental Status NaHCO3: If Blood pH <7.1 Elevated Blood/Urine Ketones -------------------------------------------- Glucose Blood pH <7.3, Low Bicarb Phosphate: Controversial -------------------------------------------- Antibiotics: Respiratory InFection Prevention (Pneumonia) Same as Ketoacidosis BUT… Faster Fluid Replacement is Needed and NaHCO3 is NOT Required Hyperosmolar LiFe Threatening Medical Emergency -------------------------------------------- Hyperglycemic Generally Seen in Type II Diabetes Prophylactic Heparin Therapy: Syndrome Patients are Prone to Thrombosis (Hyperviscosity and Sluggish Circulation) Drug Drug Class Mechanism of Action Indications Adverse Effects Contraindications More With 1st Gen than 2nd Gen: Hypoglycemia Nausea/Vomiting Weight Gain Hyperglycemia in Type II Diabetes Promote Insulin Release from Pancreatic B-Cells Cholestatic Jaundice (If Diet and Exercise Fails) Sulfonylureas Close K+ Channels in B-Cell Membrane --> Depolarization Introlerance to Alcohol (DisulFiram-Like Reaction) ------------------------ -------------------------------------------------- --> Ca2+ InFlux --> Insulin Release (Chlorpromamide) 1st Gen: Well-Absorbed Orally Type I Diabetes: ------------------------------------------------------------------ Cross Placenta: Fetal Hypoglycemia Tolbutamide Given 30- Minutes Prior to Meal SulFonylureas Require SOME Islet Reduce Serum Glucagon Level ------------------------------------------------------------------ Acetohexamide 90%-99% Bound to Plasma Protein Function to Produce EFFect Oral Hypoglycemic Agent: ------------------------------------------------------------------ Drug Interactions: Chlorpropamide (Can be Displaced) ------------------------------------------------- Tolazamide Insulin Secretagogue Short-Acting: Displace from Protein Binding: Hypoglycemia Metabolized by Liver Patients with Renal/Liver Disease ----------------------------- Tolbutamide (Safest for Elderly) Phenylbutazone Salicylates SulFonamides Secreted in Urine -------------------------------------------------- 2nd Gen: Intermediate Acting: Inhibit Metabolism/Excretion: Hypoglycemia -------------------------------------------------- Pregnancy (Insulin Only) Glipizide Acetohexatide Tolazamide Glipizide Glyburide Phenylbutazone Salicylates SulFonamides WARFARIN Glyburide Elderly: Tolbutamide Long-Acting: Synergize With/Prolong Action: Hypoglycemia Glimiperide Dangerous: Chlorporpamide Chlorpropamide Glimepiride Salicylates Propranolol Lithium Alcohol Renal Patients: Glipizide/Tolbutamine Induce Metabolism: Hyperglycemia Phenobarbital Phenytoin RiFampin Chronic Alcoholism Oppose Action/Suppress Insulin Release: Hyperglycemia Corticosteroids Diazoxide Thiazide Birth Control Rapid Onset Shorter Duration than Sulfonylureas Meglitinide Analog ---------------------------------------------- (Repaglinide) Safe For Patients with Oral Hypoglycemic Agent: Block ATP-Dependent K+ Channels Hypoglycemia Hepatic InsuFFiciency D-Phenylalanine Renal InsuFFiciency Insulin Secretagogue (Same Mechanism as SulFonylureas) Weight Gain (Metabolized in the Liver) Derivative ---------------------------------------------- (Nateglinide) EFFective in Early Insulin Release (AFter Meals) --> Post-Prandial Glucose Regulators Drug Drug Class Mechanism of Action Indications Adverse Effects Contraindications Improve Target Cell Reponse to Insulin WITHOUT Increasing Pancreatic Insulin Secretion Gi Disturbances:
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