Chapter 43
Antidiabetic Drugs
Revised 11/10
Diabetes
A complicated, chronic disorder
characterized by insufficient insulin
production or by cellular resistance
to insulin
Two Types of Diabetes
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Type 1—insulindependent diabetes
mellitus (IDDM)
Insulin produced in
insufficient amounts
Requires insulin
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Type 2—non-insulindependent diabetes
mellitus (NIDDM)
Decreased production
of insulin or decreased
cell sensitivity to insulin
May be treated with
oral drug and/or insulin
Four Pillars of Management of
Diabetes
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Meal planning referred to as medical
nutrition therapy
Activity and exercise
Medication
Self monitoring of blood glucose
(SMBG)
Insulin
A hormone produced by the pancreas
that acts to maintain blood glucose
levels within normal limits
Insulin is a high alert medication
Insulin
Essential for the use of glucose in
cellular metabolism and for proper
protein and fat metabolism
Insulin
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A hormone produced by the beta cells of the
pancreas
Controls the use of glucose, protein, and fat
in the body
Lowers blood sugar by inhibiting glucose
production by the liver
FA Davis, FON, onset, peaks, duration. See
handout from pharm 1 (corrections made)
Insulin
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Available as purified extracts from beef
and pork pancreas (used infrequently)
Synthetic insulins, such a human insulin
and insulin analogs;derived from strains
of Escherichia coli (recombinant DNA),
fewer allergies with this than extracts of
beef and pork
Activates a process that helps glucose
molecules enter the cells
Stimulates the liver glycogen synthesis
Insulin (Con’t)

Used to treat diabetes mellitus and
control more severe and complicated
forms of type 2 diabetes
Insulin Injections:
Must be injected into the subcutaneous
in the legs, arms, stomachs or buttocks.
Cannot be taken orally- it’s a protein
and the stomach acid would break it
down before it could be used.
Newer forms include Insulin Pump
ADMINISTERING INSULIN BY
INJECTION
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Administered with an insulin syringe ( syringe
calibrated in units)
Various insulin syringes hold volumes of 0.3, 0.5,
and 1 mL
The standard dosage strength of insulin is 100 U/mL
Low dose insulin syringes are used to deliver insulin
in 30-50 U or less
A standard insulin syringe can administer up to 100
U of insulin
Insulin Syringe Size is ½ inch
Insulin Preparations
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See handout from Introduction to
Pharmacology
Text, page 411
New insulin Levemir (similar to Lantus,
cannot mix with other insulins)
Considered a basal insulin like NPH and
Lantus (covers the body’s basal metabolic
needs in the absence of food)
Onset, Peak, and Duration of
Action
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Define onset, peak and duration
Refer to Handout from Introduction to
Pharmacology
Text, page 411, must memorize onset, peak
and duration of each type of insulin (review
of introduction to pharmacology)
Hypoglycemia reactions can occur anytime
but most common during peak (treat with OJ,
hard candy, glucose tabs, glucagon, Glucose
10% & 50% IV). Make sure patient has
swallowing and gag reflexes for po method)
Insulin Contraindications

Contraindicated if patient has
hypersensitivity to any ingredient in the
product (older preparations made with
beef and pork) and if the patient is
hypoglycemic
Precautions

Used cautiously with renal and hepatic
impairment and during pregnancy and
lactation
Interactions
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See Display 43-1 Drugs that Decrease
and Increase the Hypoglycemic Effect
of Insulin, page 412
Include as nursing considerations
Also review on page 412 signs and
symptoms of hypoglycemia and
hyperglycemia
Drugs that Decrease the
Hypoglycemic Effect of Insulin
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AIDS antivirals
Albuterol
Contraceptives
Corticosteroids
Estrogens
Diuretics
Epinephrine
Thyroid hormones
Drugs that Increase the
Hypoglycemic Effect of Insulin
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Alcohol
Ace inhibitors
Oral antidiabetic drugs
Calcium
Clonidine
Lithium
MAOIs
Salicylate
Sulfonimides
Tetracycline
MIXING INSULINS
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Insulins tend to bind and become
equilibrated
Inject within 5 minutes of mixing
Regular which is additive free, is
combined with intermediate-acting
insulin such as Humulin
Mixing Insulins
Promoting Optimal Response
to Insulin Therapy
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Will be individualized
Expect adjustments when under stress
and with any illness, particularly
illnesses resulting in nausea and
vomiting
Examples of Insulin
Administration using a Sliding
Scale
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Handout from Morton Hospital (use as
an example)
Double sided (reverse has how to treat
hypoglycemia)
Follow agency protocol
Preparing Insulin for
Administration
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Current insulin bottle at room
temperature, except Lantus which is
refrigerated
Check expiration (dated at time of
opening and used for a one month
period)
Do not shake, rotate gently, invert
gently for those insulins in suspension
Rotating Injection Sites
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Rotating sites prevents lipodystrophy (atrophy
of subcutaneous fat)
Lipodystrophy interferes with absorption of
insulin
Appears as a slight dimpling or pitting of SC fat
Ask patient about particular site rotation
schedule
Newer philosophy involves using all sites in one
area before moving to another body part
See text, page 551
Body Diagram of Appropriate
Sites
Methods of Administering
Insulin
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Parenteral-subcutaneous or intravenous
Insulin Pump
Inhalation- research continues, Exubria
(Pfizer) taken off market, Dec. 2008
due to risks with lungs/complications
Insulin Pumps
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Newer technology. Attempts to mimic the
body’s normal pancreatic function.
Only regular insulin is used.
Needle inserted subcutaneously and left in
place for 1-3 days
Battery operated.
Amount of insulin injected can be adjusted
according to blood glucose levels (monitored
4-8 times a day)
Inhaled Insulin- Recently
taken off market- only FYI
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Food and Drug Administration approved the first noninjectable
insulin in a dry inhalation powder in early 2006 (Exubera)
Exubera was a rapid acting insulin and must be taken within
10 minutes of a meal. Peaks 90-120 minutes similar to rapid
acting analogs (Humalog, Novolog, Apidra). Duration was 6
hours.
Contraindicated in people who smoke or recently stopped
within 6 months, or poorly controlled lung disease, and during
pregnancy.
Dosing- not supplied in international units, rather 1 mg or 3
mg blisters. (1 mg blister equivalent to 3 units; 3 mg blister
equivalent to 8 units (physics/ cloud burst)
Directions: load, apply pressure, inhale, hold breath for 5
seconds at the end of inhalation.
Monitoring and Managing
Adverse Reactions

Must know signs and symptoms of
hypoglycemia and hyperglycemia
Signs of Hyperglycemia
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3 Ps- polyuria, polydipsia, polyphagia
Blurred vision
Fatigue, lethargy, drowsiness
Headache
Abdominal pain
Dry, flushed, warm skin
Ketonuria
Acetone breath (fruity odor due to ketones)
Rapid, weak pulse
Coma
Signs of Hypoglycemia
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Headache
Hunger
Fight or flight
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Neuroglycopenia
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Shaky
Cold sweat (cool, clammy skin, diaphoresis)
“Cold and clammy, need some candy”
Palpitations
Tachycardia
Irritability, nervousness, anxiety
Confusion
Blurred vision
General weakness
Drowsiness
Seizures, coma
CAUTION

Autonomic neuropathy: No symptoms
Educating the Patient and
Family
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Review principles of teaching the adult patient
Noncompliance may be a problem with some patients
(may be related to lack of understanding of disease
process or medications or management)
Establish a thorough teaching plan for patients newly
diagnosed, for patients with changes in treatment
plan
Include teaching on diet, glucose monitoring,
medications, adverse reactions, hygiene, exercise,
sick day protocols, medic alert bracelets
Nursing Diagnoses
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Anxiety and Fear
Impaired Adjustment, Coping, and
Altered Health Maintenance
Acute confusion related to
hypoglycemic reaction
Glucose, risk for instable blood glucose
Oral Drugs
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Sulfonylureas
Biguanides
Alpha-glucosidase inhibitors
Meglitinides
Thiazolidinediones
Hormone Mimetic Agents –many different actions
to help lower blood sugar levels, see page 424;
Januvia, Byetta, Symlin
See Summary of Drugs- pages 556-557
Sometimes oral antidiabetic drugs are used in
combinations
Sulfonylureas
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Examples—tolbutamide (Orinase), glipizide (Glucotrol), glyburide
(Diabeta, Micronase), glimepiride (Amaryl)
Act to lower blood glucose by stimulating the beta cell to release
insulin
Adverse Reactions—hypoglycemia, anorexia, nausea, vomiting,
epigastric discomfort, weight gain, heartburn, weakness and
numbness of extremities
Nursing considerations:Glucotrol given 30 minutes before a meal,
glyburide is given with breakfast. Avoid alcohol (has a disulfiram-like
reaction(Antabuse)-flushing, throbbing in head and neck, respiratory
difficulty, vomiting, sweating, chest pain and hypotension,
arrhythmias, and unconsciousness
Secondary failure may occur (may lose effectiveness,; may prescribe
another sulfonylureas or add another oral antidiabetic drug such as
metformin
Biguanides
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Example—metformin (Glucophage)
Action—reduces hepatic glucose production and
increases insulin sensitivity to muscle and fat cells. May
cause weight loss, favorable SE includes lowering of
triglycerides and LDL cholesterol
Adverse Reactions—gastrointestinal (GI) upset
(abdominal bloating, nausea, cramping, diarrhea, etc),
metallic taste, hypoglycemia (rare)
Rare SE: lactic acidosis with kidney failure
Nursing implications; give with meals. Glucophage XR
given once daily with evening meal. Glucophage must
be stopped 48 hours before and after radiology studies
that use iodine. Monitor renal function.
Alpha-Glucosidase Inhibitors
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Examples—acarbose, miglitol
Action—lower blood sugar by delaying
carbohydrate digestion and absorption
Adverse Reactions—bloating and
flatulence, abdominal pain, diarrhea
Nursing considerations: given with first
bite of the meal because food increases
absorption. Monitor liver function
Meglitinides
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Examples—nateglinide (Starlix), repaglinide (Prandin)
Action—stimulate insulin release from the pancreas in
response to a glucose load. Has short duration of
action, thus reduces the potential for hypogylcemic
reactions.
Adverse Reactions – upper respiratory infection (URI),
headache, rhinitis, bronchitis, headache, back pain,
hypoglycemia
Nursing considerations: give 15-30 minutes before
meal. Disadvantage- need to take up to 4 doses a day
Thiazolidinediones
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Examples—rosiglitazone (Avandia-December 2008, FDA
announced safety issues and increase of cardiac related
deaths, off market), pioglitazone (Actos)
Action—decrease insulin resistance and increase insulin
sensitivity by modifying several processes. . Increases
sensitivity of muscle and fat tissue to insulin
Adverse Reactions—aggravated diabetes mellitus, URI,
sinusitis, headache, pharyngitis, myalgia, diarrhea, back
pain
Nursing considerations: delay of a meal for as little as 30
minutes can cause hypoglycemia. Monitor liver function.
Reduces the blood level of some oral contraceptives
Combination Agents
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Metaglip- glipizide and metformin
Glucovance-glyburide and metformin
Actoplus Met- pioglitazone and
metformin
Avandamet- rosiglitazone and
metformin
Duetact- Pioglitazone and glimepiride
Avandaryl- rosiglitzone and glimepride
Pharmacologic Algorithm for
Treating Type 2 Diabetes
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See text, page 558
Emergency Medications to
ELEVATE Glucose
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Glucagon IM (glucagon is a hormone
produced by the alpha cells of the pancreasstimulates the conversion of glycogen to
glucose in the liver. . return to consciousness
within 5-20 minutes, if no response, suggests
a lack of available hepatic glycogen and will
need to administer IV dextrose)
IV D50
Key Concepts for Insulin
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Know which insulins can or cannot be mixed (Lantus cannot be mixed)
Concentration of U100 most commonly used
Check expiration date, name, concentration each time
Rotate cloudy suspensions
Check orders/verify with 2nd nurse per agency protocol
No air bubbles
Rotate sites
Familiarize self with needle size, pens, dials, pumps
Hypoglycemic reactions can occur anytime, but most common during insulin
peak time
Proper storage-room temperature if used within one month, refrigerate up to
3 months
Prefilled syringes are stable for one week
Insulin needs change if stressed or ill
Travel with supplies and snacks
Know signs and symptoms of hyper and hypoglycemia
Case Study
Timothy Jones is admitted to your unit
with a diagnosis of new onset type 1
diabetes mellitus. His blood sugars have
stabilized and he is beginning to ask
questions. How would you answer the
following questions?
What is diabetes?
Why can’t I be on pills instead of insulin?
Why do I have to test my blood sugars?
What should I do if it is too high or too low?
Does insulin have any side effects? What
should I watch for?
Develop a Care Plan for Mr. Jones, a 22
year old newly diagnosed with Type 1
diabetes
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MD orders include:
Test blood sugars ac and hs
Regular insulin sc coverage
ac and hs
Sliding scale:
< 200 no coverage
201-250---2 u
251-300---4 u
301-350---6 u
351-400---8 u
> 400 Call MD
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Humulin N 20 units sc 7:30
am
1800 ADA diet
Videos or Workbook Activities
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Insulin Injections
Novo Pen 3
Workbook, chapter 43
Review of Introduction
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NCLEX and Pharmacology
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Generic names for medications, may use
brand name if only one brand name
available
May give clues such as drug classification
May ask question(s) by drug classification
Core Concepts in
Pharmacology
Second Edition
Norman Holland
and
Michael Patrick Adams
Chapter 29
Drugs for Endrocrine
Disorders
The Endocrine System
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Consists of glands that secrete hormones
Hormones are released as changes in the
body occur
Hormones are transported by the blood
through the body
One hormone may control the secretion of
another hormone
Hormone action is controlled by a negative
feedback mechanism
Utilization of Hormones
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Replacement therapy for patients who
are unable to secrete sufficient
quantities of endogenous hormones
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Thyroid hormone - following a
thyroidectomy
Insulin - when the pancreas is not
functioning
Given in the same low-level amounts as if
secreted by the gland
Utilization of Hormones
(cont’d)
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Cancer chemotherapy
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Testosterone for breast cancer
Estrogen for testicular cancer
Given in doses much larger than normally secreted
by the gland
Used to produce an exaggerated response
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Hydrocortisone - suppress inflammation
Estrogen or progesterone - prevent ovulation and
pregnancy
The Hypothalamus and the
Pituitary Gland

Hypothalamus secretes releasing factors
(hormones) that travel by way of the blood to
the anterior pituitary
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Releasing factors tell pituitary which hormone to
release
Pituitary gland releases the appropriate hormone
into the blood, which travels to its target organ to
cause its effect
Thyrotropin-releasing hormone (hypothalamus)
Thyroid-stimulating hormone (pituitary gland)
Thyroid hormone (thyroid gland-target organ)
Pancreas
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Essential to both the digestive and endocrine
systems
Exocrine function - secretes several enzymes
into the duodenum via the pancreatic duct
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Assist in chemical digestion
Endocrine function - islets of Langerhans
secrete glucagon and insulin directly into the
blood
Insulin Secretion
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Regulated by a number of chemicals,
hormonal and nervous factors
Glucose in the blood stimulates islets of
Langerhans in the pancreas to secrete insulin
Insulin affects carbohydrate, lipid, and
protein metabolism
Without insulin glucose can’t enter the cells to
be used for fuel
Glucagon
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Secreted by the islets of Langerhans in
the pancreas
Secreted when levels of glucose in the
blood are low
Maintains adequate levels of glucose in
the blood between meals
Moves glucose from liver to the blood
Type 1 Diabetes Mellitus
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Aka juvenile-onset diabetes
Lack of insulin secretion by the pancreas
Genetic component
Signs and symptoms
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Hyperglycemia
Polyuria
Polyphagia
Polydipsia
Glucosuria
Weight loss
Fatigue
Type 2 Diabetes Mellitus
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Aka adult-onset diabetes
Pancreas secretes insulin in small
amounts but insulin receptors in target
cells insensitive or resistant to insulin
Common in overweight clients and
those having low HDL-cholesterol and
high triglyceride levels
Untreated Both Type 1 and
Type 2 Can Produce Serious
Long-Term Damage
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To blood vessels in heart, brain,
kidneys, eyes, legs, and feet
To peripheral nerves in hands and feet
Type 1 Diabetes - Treatment

Type 1 diabetes is treated with a
combination of diet, exercise, and
insulin
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Meals regularly, every 4–5 hours, to
regulate blood glucose levels
Regular, moderate exercise to help cells
respond to insulin
Insulin therapy to keep blood glucose
levels within normal limits
Type 2 Diabetes - Treatment
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Controlled through lifestyle changes and
oral hypoglycemic agents
Proper diet and exercise can sometimes
increase sensitivity of insulin receptors
Type 2 Diabetes - Treatment
(cont’d)
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Oral hypoglycemic drugs
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When diet and exercise have failed to decrease
the blood glucose
Five classes of oral hypoglycemics
Classifications based on chemical structure and
mechanism of action
Therapy initiated with a single agent
Oral hypoglycemics are effective when taken on a
regular basis
Drug Profile - Oral
Hypoglycemic
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Glipizide (Glucotrol), second generation
sulfonylurea
Actions and uses
Adverse effects and interactions
Mechanism in action
Insulin Therapy

Five types of insulin available, differing
in onset of action and duration of action
Table 29.2
Insulin Preparations
Table 29.2 (continued)
Insulin Preparations
Insulin Therapy (cont’d)
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Most insulin today obtained through
recombinant technology
Routes of administration:
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Most common route is subcutaneous
Only regular insulin can be given IV
Insulin pumps are being used
Research to discover new routes - nasal spray
Doses of insulin highly individualized
Self-monitoring of blood glucose is important
Drug Profile - Insulin
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Regular insulin (Humulin R, Novolin R)
Actions and uses
Adverse effects and interactions
Mechanism in action
Hypoglycemia Can Result
From:
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Insulin overdose
Improper timing of insulin dose
Skipping a meal
Signs and Symptoms of
Hypoglycemia
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Tachycardia
Confusion
Sweating
Drowsiness
Without quick treatment you will see
convulsions, coma, and death
Hyperglycemia Can Result
From:
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Underdose of insulin or hypoglycemic agent
Signs and symptoms of hyperglycemia
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Fasting blood glucose greater than 126 mg/dl
Polyuria
Polyphagia
Polydipsia
Glucosuria
Weight loss/gain
Fatigue
Thyroid

Follicular cells secrete thyroid hormones
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Thyroxine (tetraiodothyronine or T4)
Triiodothyronine (T3)
Iodine is necessary for the production of
these hormones
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Found in iodized salt
Parafollicular cells secrete calcitonin

Involved with calcium homeostasis
Thyroid Function
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Multiple levels of hormonal control
TRH stimulates the pituitary gland to
produce and secrete TSH
TSH stimulates the thyroid gland to
produce and secrete thyroid hormones
into the blood
Thyroid Function (cont’d)
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When thyroid hormones reach a certain
level in the blood, the secretions of TRH
and TSH are slowed down
This slowing down is known as a
negative feedback loop
If thyroid hormone levels in the blood
drop then more TRH and TSH will be
secreted
Thyroid Hormone Affects
Every Cell in the Body
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Regulates basal metabolic rate
Critical to growth of the nervous system
Hypothyroidism
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Causes of insufficient secretion of TSH
or thyroid hormone
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Consequences of autoimmune disease
Surgical removal of thyroid gland
Aggressive treatment with antithyroid
drugs
Types of Hypothyroidism
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Cretinism - children
Signs and symptoms of cretinism
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Dwarfism
Severe mental retardation
Myxedema - adults
Myxedema - adults
Types of Hypothyroidism
(cont’d)
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Signs and symptoms of myxedema
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Slowed body metabolism
Slurred speech
Bradycardia, weight gain
Low body temperature
Intolerance to cold
Treatment for Both Types Is
Natural or Synthetic Thyroid
Hormone
Hyperthyroidism - Too Much
Thyroid Hormone Secreted
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Graves’ disease - severe form of
hyperthyroidism
Signs and symptoms
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Increased body metabolism
Tachycardia, weight loss
High body temperature
Anxiety
Hyperthyroidism - Treatment
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Thyroidectomy if due to tumor
Given antithyroid agents to kill or
inactivate some of the thyroid cells,
sometimes before thyroidectomy to
decrease bleeding during surgery
Ionizing radiation to kill or inactivate
thyroid cells
Adrenal Gland
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Cortex
Medulla
Adrenal Cortex

Secrete several classes of steroid
hormones
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Glucocorticoids
Mineralocorticoids
Androgens
The three hormones are referred to as
corticosteroids or adrenocortical
hormones
Mineralocorticoid
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Aldosterone
Increases the renal absorption of
sodium in exchange for potassium
Glucocorticoid
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CRF secreted from the hypothalamus
Causes release of ACTH from the
pituitary gland
Glucocorticoids are released from the
adrenal cortex
As the glucocorticoid level rises,
hormones are shut off
Glucocorticoids Affect
Metabolism of Nearly Every Cell
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During long-term stress, mobilize the
formation of glucose
Increase the breakdown and utilization
of proteins and lipids
Potent anti-inflammatory effect
Promote homeostasis of the
cardiovascular, nervous, and
musculoskeletal systems
Adrenocortical Insufficiency
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Decrease production of corticosteroid
Causes
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Hyposecretion by adrenal cortex
Inadequate secretion of ACTH from pituitary
Signs and symptoms
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Hypoglycemia
Fatigue
Hypotension
GI disturbances
Primary adrenocortical
insufficiency - Addison’s
Disease
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Quite rare
Deficiency of both glucocorticoids and
mineralocorticoids
Treated with glucocorticoid replacement
therapy
Secondary Adrenocortical
Insufficiency
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Relatively common
Long-term therapy with glucocorticoids
that is abruptly discontinued
Treated with glucocorticoid replacement
therapy
Insulin
Table 29.2
Insulin Preparations
Table 29.2 (continued)
Insulin Preparations
Oral Hypoglycemics
Table 29.3
Oral Hypoglycemics
Table 29.3 (continued)
Oral Hypoglycemics
Table 29.3 (continued)
Oral Hypoglycemics
Thyroid and Antithyroid
Agents


The correct dose is highly individualized
Requires periodic adjustments
Table 29.4
Thyroid and Antithyroid Medications
Hypothyroidism Slows the
Body’s Metabolism

Administration of thyroid hormone
reverses that effect
Drug Profile - Thyroid Agent
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Levothyroxine (Synthroid)
Actions and uses
Adverse effects and interactions
Mechanism in action
Hyperthyroidism Speeds the
Body’s Metabolism

Administer drugs that kill or inactivate
thyroid cells
Drug Profile - Antithyroid
Agent
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Propylthiouracil (Propacil)
Actions and uses
Adverse effects and interactions
Mechanism in action
Glucocorticoids Are Used to
Treat:

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Inflammatory and immune responses
Disorders that may be treated with corticosteroids
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Allergies, seasonal rhinitis, asthma
Contact dermatitis and rashes
Hodgkin’s disease, leukemias, lymphomas
Shock
Rheumatoid arthritis, ankylosing spondylitis, bursitis
Ulcerative colitis, Crohn’s disease
Hepatic, neurological, renal disorders with edema
Following transplant surgery
Significant Adverse Effects
Can Occur During Long-Term
Therapy

Known as Cushing’s Syndrome
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Adrenal atrophy
Osteoporosis
Increased risk of infections
Delayed wound healing
Peptic ulcer
Accumulation of fat around shoulders and neck
Mood and personality changes
Drug Profile - Glucocorticoid
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Hydrocortisone (Cortef)
Actions and uses
Adverse effects and interactions
Mechanism in action
Growth Hormone - Aka
Somatotropin
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Secreted by pituitary gland
Stimulates growth of cell
Deficiency in children
Dwarfism with no mental impairment
Growth Hormone Medications
for Dwarfism in Children

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Somatrem (Protopin)
Somatropin (Humantrope)
Not approved to stimulate growth in
short children
Antidiuretic Hormone
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Produced by the hypothalamus
Secreted from the posterior pituitary
gland
Increases water absorption by kidneys
Raises blood pressure if secreted in
large amounts
Diabetes insipidus - deficiency of ADH
Treatment of Diabetes
Insipidus

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Vasopressin (Pitressin)
Desmopressin (DDAVP, Stimate)
Lopressin (Diapid)
Desmopressin used for enuresis - nasal
spray