Lehne: Pharmacology for Nursing Care, 5th Edition

Instructor’s Manual Chapter Outlines

Chapter 54: Drugs for Diabetes Mellitus

I. Diabetes Mellitus: Overview of the Disease and Its Treatment—Production of large volumes
of glucose-rich urine; a disorder of carbohydrate metabolism; symptoms from deficiency of
insulin or from resistance to insulin’s actions; symptom of sustained hyperglycemia
polyuria, polydipsia, ketonuria, and weight loss; over time leads to hypertension, heart
disease, blindness, renal failure, neuropathy, amputations, impotence, and stroke
A. Types of Diabetes Mellitus—Two major types (type 1 and type 2) plus gestational
diabetes
1. Type 1 (previously known as insulin-dependent diabetes mellitus)—Usually
begins in childhood with abrupt symptoms; pancreatic beta cells are destroyed
2. Type 2 (previously known as non-insulin–dependent diabetes mellitus)—Most
prevalent form of DM; obesity present; little risk of ketoacidosis; symptoms
result from insulin resistance and altered secretion
B. Short-Term Complications of Diabetes—Usually with type 1, see hyperglycemia or
hypoglycemia; ketoacidosis is potentially fatal for untreated hyperglycemia
C. Long-Term Complications of Diabetes—Most problems due to disruption of blood
flow from macro- or microvascular damage; rigorous control decrease in long-term
complications
1. Macrovascular disease—Cardiovascular complications leading cause of death;
atherosclerosis develops early in DM
2. Microvascular disease—Microangiopathy common kidney damage and
blindness
3. Retinopathy—DM major cause of blindness
4. Nephropathy—Proteinuria, reduced GFR, HTN
5. Neuropathy—Nerve degeneration begins early in DM but symptoms absent
for years
6. Amputations—DM responsible for more than 50% of lower limb amputations
7. Impotence—13% males and 8% in females
8. Gastroparesis—Affects 20%–30% of DM patients
D. Diabetes and Pregnancy—Difficult to control DM during pregnancy because of
placenta-producing hormones that antagonize insulin’s actions; production of cortisol
increases threefold; hyperglycemia in mother stimulates secretion of fetal insulin;
gestational diabetes is diabetes that appears during pregnancy and then subsides
rapidly after delivery
E. Diagnosis of Diabetes
1. Fasting plasma glucose (FPG) test—Administer 8–10 hours after last meal;
normal levels are less than 110 mg/dL; if greater than 126 mg/dL, DM
indicated
2. Casual plasma glucose test—Should be less than 200 mg/dL; if patient has
symptoms, DM is diagnosed

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3. Oral glucose tolerance test—When DM suspected but not definitely

diagnosed; give oral glucose load of 75 gm and measure plasma glucose levels
1 and 2 hours later (nondiabetics have glucose levels of less than 200 mg/dL
at 1 hour and below 140 mg/dL at 2 hours)
F. Overview of Treatment
1. Type 1—Goal is to maintain glucose levels within an acceptable range using
diet, blood glucose monitoring, exercise, and insulin replacement (diet
balanced with insulin replacement is cornerstone of treatment)
2. Type 2—Goal is to maintain glucose levels within an acceptable range with
core of treatment being diet and exercise alone; if this fails, add
pharmacotherapy; drug selection—stepwise approach: (1) lifestyle changes;
(2) one oral drug; (3) use two agents; (4) oral agent plus insulin; (5) insulin
alone; (6) insulin plus a thiazolidinedione
G. Monitoring Treatment—To determine whether glucose levels are in a safe range
1. Self-monitoring of blood glucose (SMBG)—The standard for self-monitoring
with target values for blood glucose of 80–120 mg/dL before meals and 100–
140 mg/dL after meals
2. Urine glucose monitoring—Old method; limited use because of poor
correlation between urine glucose and blood glucose levels
3. Glycosylated Hemoglobin—Hemoglobin A1C reflects average glucose levels
over extended time (target is for 7% or less)
4. Fructosamine—Index of 1–2 weeks; want 30 mmol/L or less for good control
II. Insulin
A. Physiology
1. Structure—See Figure 54-1 in the text
2. Biosynthesis—Synthesized in pancreas by beta cells in the islets of
Langerhans; evidence of c-peptide in blood indicates pancreas still producing
some insulin
3. Secretion—Stimulus is glucose; sympathetic nervous system provides
additional control of insulin release (activation of beta2 adrenergic receptors
promote secretion, and activation of alpha-adrenergic receptors inhibit insulin
release)
4. Metabolic actions—Actions are primarily anabolic to conserve energy and
build up stores of energy by cellular transport of glucose, amino acids,
nucleotides and potassium; secondarily, insulin promotes synthesis of
complex organic molecules
B. Metabolic Consequences of Insulin Deficiency—Body goes into catabolic mode, in
which glycogen is converted into glucose, proteins degraded into amino acids, and
fats converted to glycerol and free fatty acids; insulin deficiency promotes
hyperglycemia by three ways (increased glycogenolysis, increased gluconeogenesis,
and reduced glucose utilization); diabetic ketoacidosis occurs secondary to disruption
of glucose and fat metabolism
C. Therapeutic Uses—IV for diabetic ketoacidosis and to treat hyperkalemia
D. Preparations
1. Types of insulin—Five types (see Tables 54-5 and 54-6 in the text for
specifics)

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a. Regular (natural) insulin

b. Lispro insulin (Humalog)—New rapid-acting form of insulin
c. Neutral protamine Hagedorn (NPH) insulin—Conjugated regular
insulin with protamine to retard absorption
d. Lente insulin and Ultralente insulin—produced by complexing regular
insulin with zinc, which changes solubility
2. Sources of insulin
a. Beef or pork pancreas—Antibodies can develop to these; beef
pancreas insulin no longer produced in U.S.
b. Recombinant DNA technology—Produces those listed as human
3. Concentration—100 or 500 U/ml in U.S. now; usually use 100 U/ml
E. Administration and Storage
1. Usual routes of administration—SC; only regular insulin has the potential of
IV or IM in emergencies
2. Preparation for injection—Except for regular, all insulins are suspensions, and
vials should be rolled gently just before loading syringe
3. Sites of injection—SC of upper arms, thighs, and abdomen; rotate sites with 1
inch between sites
4. Mixing insulins—Can mix regular with all except lispro insulin; draw up
regular insulin first; now a mixture of 70% NPH with 30% regular or 50/50
comes prepared for convenience
5. Storage—Unopened vials stored in refrigerator; use up to expiration date
when refrigerated unopened; once opened, store at room temperature for up to
1 month; prefilled syringes stable for at least 1 week (store vertically with
needle pointing up)
6. Alternative methods of insulin delivery
a. Jet injectors—No needle; expensive; bruises can occur
b. Pen injectors
c. Portable insulin pumps—Computerized device to deliver basal
infusion of regular plus bolus before meals; very expensive
d. Implantable insulin pumps—Superior control, are still experimental
and not for general use yet
e. Intranasal insulin—Experimental, rapid onset and brief duration with
only 10% of dose absorbed
F. Insulin Therapy of Diabetes Mellitus
1. Tight glucose control—Benefits and drawbacks
a. Benefits—Tight control maintains glucose within a normal range,
reducing long-term complications
b. Drawbacks—Concern for hypoglycemia, patients gain more weight,
increased complexity of therapy, expense
2. Dosage—Match to insulin needs based on calories, stress, growth spurts, and
pregnancy with ranges from 0.1 U/kg to >2.5 U/kg/day (for NIDDM, the
doses may range from 0.2 to 0.6 U/kg/day)
3. Dosing schedules—Helps determine extent to which tight control is achieved
(see Table 54-7 in the text)
a. Conventional therapy—Dosing does not provide tight control

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b. Intensified convention therapy (ICT)—Significant feature is

adaptability using long-acting and regular insulin
c. Continuous subcutaneous insulin infusion (CSII)—Use of regular
insulin
4. Achieving tight glucose control—Adaptability of drugs; attention to all
elements of program; defined glycemia target; home glucose monitoring
3–5 times/day; high degree of motivation and extensive patient education,
including nature of diabetes, importance of tight control, components of
treatment, purchasing of materials and drugs, importance of arbitrary
changes between insulins, insulin storage, calculations of dosages,
techniques of administration, and methods of monitoring
G. Complications of Insulin Therapy
1. Hypoglycemia—Glucose of <50 mg/dL; know signs of hypoglycemia;
symptoms depend on how rapid the change in glucose level occurs
2. Other complications—Lipodystrophies and allergic reactions
H. Drug Interactions
1. Hypoglycemic agents—Intensify hypoglycemia; drugs include sulfonylureas,
troglitazone, alcohol, and beta-adrenergic blockers
2. Hyperglycemic agents—Thiazide diuretics, glucocorticoids, and
sympathomimetics counter effects of insulin (will need increased dosage of
insulin with these drugs)
3. Beta-adrenergic blocking agents—Delays awareness of insulin-induced
hypoglycemia by masking symptoms associated with SNS
III. Oral Hypoglycemics—Five families for treatment of NIDDM to be used after program of
diet and exercise have been tried
A. Sulfonylureas—Two generations of these drugs with second generation more potent,
but example is tolbutamide (Orinase), a first-generation drug, which stimulates
release of insulin from pancreatic islets; adverse effects include hypoglycemia; oral
agents should be avoided during pregnancy or by nursing women; controversy exists
regarding cardiovascular reactions; alcohol combined with tolbutamide produces
disulfiram-like reaction; drugs that intensify hypoglycemia include NSAIDS,
sulfonamide antibiotics, ethanol, ranitidine, and cimetidine; beta blockers may
suppress insulin release and mask symptoms of hypoglycemia
B. Tolbutamide (Orinase)—Stimulates the release of insulin from pancreatic islets
C. Meglitinides: Repaglinide (Prandin)—Lowers glucose levels by stimulating release of
insulin from the pancreas; only for type 2 DM; rapid absorption; generally well
tolerated but can get hypoglycemia
D. Biguanides: Metformin (Glucophage)—Approved in 1994 after similar products were
withdrawn from the market because of lactic acidosis (not true for metformin, but this
drug does cause frequent GI disturbances); metformin lowers blood glucose by
decreasing production of glucose by liver (gluconeogenesis) and not by promoting
insulin release; absorbed slowly from small intestine, excreted by kidneys; drug used
with diet and exercise, and may be combined with sulfonylureas; side effects include
decreased appetite, nausea, and diarrhea; toxicity includes lactic acidosis
E. Thiazolidinediones (“Glitazones”)—New class of drugs which increases target cells
to respond to insulin (insulin-resistant patients); readily absorbed; rare side effects but

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unknown safety for pregnancy; drug interactions (cholestyramine reduces

absorption)
1. Troglitazone—Reduces levels of oral contraceptives and terfenadine
2. Rosiglitazone (Avandia)—Another thiazolidinedione
3. Pioglitazone (Actos) —Thiazolidinedione that has a more favorable effect
on plasma lipids
F. Alpha-Glucosidase Inhibitors (Acarbose)—Delays absorption of dietary
carbohydrates, so decreases rise of blood glucose after meals by inhibiting the
enzyme that breaks down complex carbohydrates to monosaccharides; acarbose
frequently causes flatulence, cramps, abdominal distention, borborygmus, and
diarrhea and can cause decreased absorption of iron anemia; hypoglycemia does
not develop when acarbose is used alone
IV. Diabetic Ketoacidosis—Most severe manifestation of insulin deficiency
1. Pathogenesis—Derangement of glucose and fat metabolism
2. Treatment—Life-threatening emergency; restore insulin levels; correct acidosis;
replace lost water and sodium; normalize potassium and glucose levels
V. Glucagon for Insulin Overdose—Glucagon is polypeptide hormone produced by alpha cells;
increases plasma levels of glucose and relaxes smooth muscle of the GI tract; response
should occur within 20 minutes of administration; dose of 0.5 to 1.0 mg usually effective
VI. Key Points
VII. Summary of Major Nursing Implications
A. Insulin
B. Sulfonylureas

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