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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 57
Drugs for Diabetes Mellitus
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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
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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
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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
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Complications of Diabetes Short-term
Hyperglycemia and hypoglycemia Long-term
Macrovascular damage• Heart disease• Hypertension• Stroke• Hyperglycemia• Altered lipid metabolism
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Complications of Diabetes Long-term (cont’d)
Microvascular damage• Retinopathy• Nephropathy• Neuropathy• Gastroparesis• Amputation secondary to infection
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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)
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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
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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
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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 antidiabetic drugs
Many people who meet criteria for “prediabetes” never develop diabetes, even if they do not take precautions against diabetes
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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
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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
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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
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Monitoring Treatment Self-monitoring of blood glucose (SMBG) Hemoglobin A1c
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Insulin: Physiology Biosynthesis Secretion Metabolic actions Metabolic consequences of insulin deficiency
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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
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Insulin Concentration
100 units/mL (U-100) 500 units/mL (U-500)
Mixing insulins NPH with short-acting insulins Short-acting insulin drawn first
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Administration Subcutaneous injection
Syringe and needle Pen injectors Jet injectors
Subcutaneous infusion Portable insulin pumps Implantable insulin pumps (experimental)
Intravenous infusion
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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
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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
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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
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Insulin Therapy of Diabetes Dosage Dosing schedules
Conventional therapy Intensive conventional therapy Continuous subQ infusion
Achieving tight glucose control
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Complications of Insulin Treatment Hypoglycemia Lipohypertrophy Allergic reactions Hypokalemia Drug interactions
Hypoglycemic agents Hyperglycemic agents Beta-adrenergic blocking agents
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Oral Hypoglycemics Biguanides
Metformin (Glucophage) Sulfonylureas Thiazolidinediones (glitazones)
Rosiglitazone (Avandia) Pioglitazone (Actos)
Meglitinides (Glinides) Repaglinide (Prandin) Nateglinide (Starlix)
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Oral Hypoglycemics Alpha-glucosidase inhibitors
Acarbose (Precose) Miglitol (Glyset)
Gliptins Combination products
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Combination Products Metformin/Glyburide Metformin/Glipizide Metformin/Saxagliptin Metformin/Pioglitazone Metformin/Repaglinide Metformin/Sitagliptin Pioglitazone/Glimepiride Rosiglitazone/Glimepiride Rosiglitazone/Metformin Sitagliptin/Simvastatin
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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
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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
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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
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Diabetic Ketoacidosis Altered glucose metabolism
Hyperglycemia Water loss Hemoconcentration
Altered fat metabolism Production of ketoacids
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Diabetic Ketoacidosis Treatment
Insulin replacement Bicarbonate for acidosis Water and sodium replacement Potassium replacement Normalization of glucose levels
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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
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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
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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
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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