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Chapter 57

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Chapter 57

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  1. Chapter 57 Drugs for Diabetes Mellitus

  2. Diabetes Mellitus: Overview of the Disease and Its Treatment • Diabetes mellitus • Greek word for “fountain” • Latin word for “honey” • Disorder of carbohydrate metabolism • Deficiency of insulin • Resistance to action of insulin • Sustained hyperglycemia, polyuria, polydipsia, ketonuria, and weight loss

  3. Types of Diabetes Mellitus • Type 1 diabetes • 5%–10% of all cases • Also called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes mellitus • Primary defect is destruction of pancreatic beta cells

  4. Types of Diabetes Mellitus • Type 2 diabetes • Most prevalent form of diabetes • Approximately 22 million Americans have it • Also called non–insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes mellitus • Insulin resistance and impaired insulin secretion

  5. Complications of Diabetes • Short-term • Hyperglycemia and hypoglycemia • Long-term • Macrovascular damage • Heart disease • Hypertension • Stroke • Hyperglycemia • Altered lipid metabolism

  6. Complications of Diabetes • Long-term (cont’d) • Microvascular damage • Retinopathy • Nephropathy • Neuropathy • Gastroparesis • Amputation secondary to infection

  7. Diabetes and Pregnancy • Before insulin: many babies born to severely diabetic women died • Factors during pregnancy • Placenta produces hormones that antagonize the actions of insulin • Production of cortisol increases threefold • Glucose can pass freely from the maternal to the fetal circulation (fetal hyperinsulinemia)

  8. Diabetes and Pregnancy • Proper glucose levels needed in pregnant patient and in fetus to prevent teratogenic effects • Fetal death frequently occurs near term • Earlier delivery is desirable • Gestational diabetes

  9. Diagnosis of Diabetes • Excessive plasma glucose is diagnostic of diabetes • Patient must be tested on two separate days, and both tests must be positive • Three tests • Fasting plasma glucose (FPG) • Casual plasma glucose • Oral glucose tolerance test (OGTT) • Hemoglobin A1c, oral glucose tolerance test

  10. Prediabetes • Impaired fasting plasma glucose between 100 and 125 mg/dL • Impaired glucose tolerance test • Increased risk for developing type 2 diabetes • May reduce risk with diet changes and exercise and possibly with certain oral antidiabeticdrugs • Many people who meet criteria for “prediabetes” never develop diabetes, even if they do not take precautions against diabetes

  11. Overview of Diabetes Treatment • Primary goal is to prevent long-term complications • Tight control of blood glucose level is important • Also important to control blood pressure and blood lipids

  12. Type 1 Diabetes • Requires comprehensive plan • Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement • Dietary measures • Total number of carbohydrates, not the type of carbohydrates, is most important • Glycemic index

  13. Type 2 Diabetes • Similar to type 1, requires comprehensive plan • Should be screened and treated for: • Hypertension, nephropathy, retinopathy, neuropathy, dyslipidemias • Glycemic control with: • Modified diet and exercise • Drug therapy

  14. Monitoring Treatment • Self-monitoring of blood glucose (SMBG) • Hemoglobin A1c

  15. Insulin: Physiology • Biosynthesis • Secretion • Metabolic actions • Metabolic consequences of insulin deficiency

  16. Seven Types of Insulin • Short duration: rapid acting • Insulin lispro (Humalog) • Insulin aspart (NovoLog) • Insulin glulisine (Apidra) • Short duration: slower acting • Regular insulin (Humulin R, Novolin R) • Intermediate duration • Neutral protamine Hagedorn (NPH) insulin • Insulin detemir (Levemir) • Long duration • Insulin glargine

  17. Insulin • Concentration • 100 units/mL (U-100) • 500 units/mL (U-500) • Mixing insulins • NPH with short-acting insulins • Short-acting insulin drawn first

  18. Administration • Subcutaneous injection • Syringe and needle • Pen injectors • Jet injectors • Subcutaneous infusion • Portable insulin pumps • Implantable insulin pumps (experimental) • Intravenous infusion

  19. Storage • Unopened vials should be stored under refrigeration until needed • Should not be frozen • Can be used until expiration date if kept in refrigerator • After opening, can be kept up to 1 month without significant loss of activity • Keep out of direct sunlight and extreme heat

  20. Storage • Mixtures of insulin in vials are stable for 1 month at room temperature and for 3 months under refrigeration • Mixtures in pre-filled syringes should be stored in refrigerator for at least 1 week and should be stored vertically with needle pointing up

  21. Insulin: Therapeutic Use • Indications • Principal: diabetes mellitus • Required by all type 1 and some type 2 patients • IV insulin for DKA • Hyperkalemia: can promote uptake of potassium • Aids in the diagnosis of GH deficiency

  22. Insulin Therapy of Diabetes • Dosage • Dosing schedules • Conventional therapy • Intensive conventional therapy • Continuous subQ infusion • Achieving tight glucose control

  23. Complications of Insulin Treatment • Hypoglycemia • Lipohypertrophy • Allergic reactions • Hypokalemia • Drug interactions • Hypoglycemic agents • Hyperglycemic agents • Beta-adrenergic blocking agents

  24. Oral Hypoglycemics • Biguanides • Metformin (Glucophage) • Sulfonylureas • Thiazolidinediones(glitazones) • Rosiglitazone (Avandia) • Pioglitazone (Actos) • Meglitinides (Glinides) • Repaglinide (Prandin) • Nateglinide (Starlix)

  25. Oral Hypoglycemics • Alpha-glucosidase inhibitors • Acarbose (Precose) • Miglitol (Glyset) • Gliptins • Combination products

  26. Combination Products • Metformin/Glyburide • Metformin/Glipizide • Metformin/Saxagliptin • Metformin/Pioglitazone • Metformin/Repaglinide • Metformin/Sitagliptin • Pioglitazone/Glimepiride • Rosiglitazone/Glimepiride • Rosiglitazone/Metformin • Sitagliptin/Simvastatin

  27. Injected Drugs (Other than Insulin) • Exenatide • Adjunctive therapy to improve glycemic control in patients with type 2 diabetes • Adverse effects • Hypoglycemia • Gastrointestinal effects • Liraglutide • Pramlintide

  28. Acute Complications of Poor Glycemic Control • Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmotic nonketotic syndrome (HHNS): Both conditions are hyperglycemic crises • Hyperglycemia is more severe in HHNS • No ketoacidosis in HHNS

  29. Diabetic Ketoacidosis • Severe manifestation of insulin deficiency • Symptoms evolve quickly in a period of hours or days • Most common complication in pediatric patients and leading cause of death • Characteristics • Hyperglycemia • Ketoacids • Hemoconcentration • Acidosis • Coma

  30. Diabetic Ketoacidosis • Altered glucose metabolism • Hyperglycemia • Water loss • Hemoconcentration • Altered fat metabolism • Production of ketoacids

  31. Diabetic Ketoacidosis • Treatment • Insulin replacement • Bicarbonate for acidosis • Water and sodium replacement • Potassium replacement • Normalization of glucose levels

  32. HHNS • Large amount of glucose excreted in urine • Dehydration and loss of blood volume • Increases the blood concentrations of electrolytes and nonelectrolytes (particularly glucose); also increases hematocrit • Blood “thickens” and becomes sluggish

  33. HHNS • Little or no change in ketoacid levels • Little or no change in blood pH • No sweet or acetone-like smell to urine or breath • HHNS occurs most frequently with type 2 diabetes mellitus with acute infection, acute illness, or some other stress

  34. HHNS • Can evolve slowly • Metabolic changes begin a month or two before signs and symptoms become apparent • If untreated, HHNS can lead to coma, seizures, and death • Management • Correct hyperglycemia and dehydration with IV insulin, fluids, and electrolytes

  35. Glucagon for Insulin Overdose • Preferred treatment is IV glucose • Immediately raises blood glucose level • Glucagon can be used if IV glucose is not available • Delayed elevation of blood glucose • Will not work in starvation • Promotes glycogen breakdown and the malnourished have little glycogen left