Chapter 43
Antidiabetic DrugsRevised 11/10
Diabetes
A complicated, chronic disorder characterized by insufficient
insulin production or by cellular resistance to insulin
Two Types of Diabetes Type 1—insulin-
dependent diabetes mellitus (IDDM)
Insulin produced in insufficient amounts
Requires insulin
Type 2—non-insulin-dependent 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
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 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 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
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 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 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
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 AIDS antivirals Albuterol Contraceptives Corticosteroids Estrogens Diuretics Epinephrine Thyroid hormones
Drugs that Increase the Hypoglycemic Effect of Insulin Alcohol Ace inhibitors Oral antidiabetic drugs Calcium Clonidine Lithium MAOIs Salicylate Sulfonimides Tetracycline
MIXING INSULINS
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
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 Handout from Morton Hospital (use
as an example) Double sided (reverse has how to
treat hypoglycemia) Follow agency protocol
Preparing Insulin for Administration 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 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
Parenteral-subcutaneous or intravenous
Insulin Pump Inhalation- research continues,
Exubria (Pfizer) taken off market, Dec. 2008 due to risks with lungs/complications
Insulin Pumps 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
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 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 Headache Hunger Fight or flight
Shaky Cold sweat (cool, clammy skin, diaphoresis) “Cold and clammy, need some candy” Palpitations Tachycardia
Neuroglycopenia Irritability, nervousness, anxiety Confusion Blurred vision General weakness Drowsiness Seizures, coma
CAUTION Autonomic neuropathy: No symptoms
Educating the Patient and Family 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
Anxiety and Fear Impaired Adjustment, Coping, and
Altered Health Maintenance Acute confusion related to
hypoglycemic reaction Glucose, risk for instable blood
glucose
Oral Drugs 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 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 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 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 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 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 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
See text, page 558
Emergency Medications to ELEVATE Glucose Glucagon IM (glucagon is a hormone
produced by the alpha cells of the pancreas-stimulates 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 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
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
Humulin N 20 units sc 7:30 am
1800 ADA diet
Videos or Workbook Activities
Insulin Injections Novo Pen 3 Workbook, chapter 43
Review of Introduction
NCLEX and Pharmacology 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 PharmacologySecond Edition
Chapter 29
Drugs for Endrocrine Disorders
Norman Hollandand
Michael Patrick Adams
The Endocrine System 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 Replacement therapy for patients
who are unable to secrete sufficient quantities of endogenous hormones 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) Cancer chemotherapy
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 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 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 Essential to both the digestive and
endocrine systems Exocrine function - secretes several
enzymes into the duodenum via the pancreatic duct Assist in chemical digestion
Endocrine function - islets of Langerhans secrete glucagon and insulin directly into the blood
Insulin Secretion 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
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 Aka juvenile-onset diabetes Lack of insulin secretion by the pancreas Genetic component Signs and symptoms
Hyperglycemia Polyuria Polyphagia Polydipsia Glucosuria Weight loss Fatigue
Type 2 Diabetes Mellitus
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
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 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
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) Oral hypoglycemic drugs
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
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) Most insulin today obtained through
recombinant technology Routes of administration:
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
Regular insulin (Humulin R, Novolin R)
Actions and uses Adverse effects and interactions Mechanism in action
Hypoglycemia Can Result From:
Insulin overdose Improper timing of insulin dose Skipping a meal
Signs and Symptoms of Hypoglycemia
Tachycardia Confusion Sweating Drowsiness Without quick treatment you will
see convulsions, coma, and death
Hyperglycemia Can Result From: Underdose of insulin or hypoglycemic
agent Signs and symptoms of hyperglycemia
Fasting blood glucose greater than 126 mg/dl Polyuria Polyphagia Polydipsia Glucosuria Weight loss/gain Fatigue
Thyroid
Follicular cells secrete thyroid hormones Thyroxine (tetraiodothyronine or T4) Triiodothyronine (T3) Iodine is necessary for the production of
these hormones Found in iodized salt
Parafollicular cells secrete calcitonin Involved with calcium homeostasis
Thyroid Function
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) 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
Regulates basal metabolic rate Critical to growth of the nervous
system
Hypothyroidism
Causes of insufficient secretion of TSH or thyroid hormone Consequences of autoimmune
disease Surgical removal of thyroid gland Aggressive treatment with antithyroid
drugs
Types of Hypothyroidism
Cretinism - children Signs and symptoms of cretinism
Dwarfism Severe mental retardation Myxedema - adults
Myxedema - adults
Types of Hypothyroidism (cont’d) Signs and symptoms of myxedema
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
Graves’ disease - severe form of hyperthyroidism
Signs and symptoms Increased body metabolism Tachycardia, weight loss High body temperature Anxiety
Hyperthyroidism - Treatment
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
Cortex Medulla
Adrenal Cortex Secrete several classes of steroid
hormones Glucocorticoids Mineralocorticoids Androgens
The three hormones are referred to as corticosteroids or adrenocortical hormones
Mineralocorticoid
Aldosterone Increases the renal absorption of
sodium in exchange for potassium
Glucocorticoid
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
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 Decrease production of corticosteroid Causes
Hyposecretion by adrenal cortex Inadequate secretion of ACTH from pituitary
Signs and symptoms Hypoglycemia Fatigue Hypotension GI disturbances
Primary adrenocortical insufficiency - Addison’s Disease
Quite rare Deficiency of both glucocorticoids
and mineralocorticoids Treated with glucocorticoid
replacement therapy
Secondary Adrenocortical Insufficiency
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
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
Propylthiouracil (Propacil) Actions and uses Adverse effects and interactions Mechanism in action
Glucocorticoids Are Used to Treat: Inflammatory and immune responses Disorders that may be treated with
corticosteroids 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 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
Hydrocortisone (Cortef) Actions and uses Adverse effects and interactions Mechanism in action
Growth Hormone - Aka Somatotropin
Secreted by pituitary gland Stimulates growth of cell Deficiency in children Dwarfism with no mental
impairment
Growth Hormone Medications for Dwarfism in Children
Somatrem (Protopin) Somatropin (Humantrope) Not approved to stimulate growth
in short children
Antidiuretic Hormone
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
Vasopressin (Pitressin) Desmopressin (DDAVP, Stimate) Lopressin (Diapid) Desmopressin used for enuresis -
nasal spray