copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 57 drugs for diabetes...

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 57

Drugs for Diabetes Mellitus

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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


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


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


Complications of Diabetes

Short-term Hyperglycemia and hypoglycemia

Long-term Macrovascular damage

• Heart disease• Hypertension• Stroke• Hyperglycemia• Altered lipid metabolism


Complications of Diabetes

Long-term (cont’d) Microvascular damage

• Retinopathy• Nephropathy• Neuropathy• Gastroparesis• Amputation secondary to infection


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)


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


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


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


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


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


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


Monitoring Treatment

Self-monitoring of blood glucose (SMBG) Hemoglobin A1c


Insulin: Physiology

Biosynthesis Secretion Metabolic actions Metabolic consequences of insulin deficiency


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


Insulin

Concentration 100 units/mL (U-100) 500 units/mL (U-500)

Mixing insulins NPH with short-acting insulins Short-acting insulin drawn first


Administration

Subcutaneous injection Syringe and needle Pen injectors Jet injectors

Subcutaneous infusion Portable insulin pumps Implantable insulin pumps (experimental)

Intravenous infusion


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


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


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


Insulin Therapy of Diabetes

Dosage Dosing schedules

Conventional therapy Intensive conventional therapy Continuous subQ infusion

Achieving tight glucose control


Complications of Insulin Treatment

Hypoglycemia Lipohypertrophy Allergic reactions Hypokalemia Drug interactions

Hypoglycemic agents Hyperglycemic agents Beta-adrenergic blocking agents


Oral Hypoglycemics

Biguanides Metformin (Glucophage)

Sulfonylureas Thiazolidinediones (glitazones)

Rosiglitazone (Avandia) Pioglitazone (Actos)

Meglitinides (Glinides) Repaglinide (Prandin) Nateglinide (Starlix)


Oral Hypoglycemics

Alpha-glucosidase inhibitors Acarbose (Precose) Miglitol (Glyset)

Gliptins Combination products


Combination Products

Metformin/Glyburide Metformin/Glipizide Metformin/Saxagliptin Metformin/Pioglitazone Metformin/Repaglinide Metformin/Sitagliptin Pioglitazone/Glimepiride Rosiglitazone/Glimepiride Rosiglitazone/Metformin Sitagliptin/Simvastatin


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


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


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



Altered glucose metabolism Hyperglycemia Water loss Hemoconcentration

Altered fat metabolism Production of ketoacids



Treatment Insulin replacement Bicarbonate for acidosis Water and sodium replacement Potassium replacement Normalization of glucose levels


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


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


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


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

copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 57 drugs for diabetes...

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