Module 6: Endocrine Medications

Tasks

Study tip: For each chapter, read "Special Concerns for Rehabilitation Patients" and "Case Study" prior to chapter content. Answer the
case study questions while you read the chapter, then compare your answers to Appendix C.
Ch. 29 (p. 453-457: Clinical uses and adverse effects of glucocorticoids)
Ch. 31 (Thyroid and Parathyroid Drugs: Agents Affecting Bone Mineralization)
Ch. 32 (Pancreatic Hormones and the Treatment of Diabetes Mellitus)

Medication Cabinet
Bone Mineralization Medications Diabetes Medications Thyroid Medications
alendronate (Fosamax) lispro (Humalog) levothyroxine (Synthroid)
calcitonin metformin (Glucophage) methimazole (Tapazole)
calcitriol (Calcijex) regular insulin (Humulin R) propranolol (Inderal)
Dexamethasone (Decadron) rosiglitazone (Avandia)
acarbose (Precose)
glipizide (Glucotrol)
isophane insulin (Humulin N)
glargine (Lantus)

Look backwards and forwards to select all of the modules that include a glucocorticoid in the cabinet (use your suffixes):
Endocrine Medications dexamethasone (Decadron)
Cardiopulmonary Medications beclomethasone (Qvar); fluticasone (Cultivate)
Pain Medications prednisone (Deltasone)
Cancer Chemotherapy prednisone (Deltasone)
Immunopharmacology prednisone (Deltasone); dexamethasone (Decadron); methylprednisolone (Medrol)
Assignment
Video case discussion applies to multiple modules and is due Nov. 20.

Assessment
Endocrine medications module is included in Examination 2 on Dec. 8. Practice questions are available.

Learning Objectives
1. Identify multi-system clinical indications and adverse effects of glucocorticoids. Table 29-2, Page 455.
1. Allergic disorders (anaphylactic reactions, drug-induced allergic reactions, severe hay fever, serum sickness)
2. Collagen disorders (acute rheumatic carditis, dermatomyositis, systemic lupus erythematosus)
3. Dermatologic disorders (alopecia areata, dermatitis, keloids, lichens, mycosis fungoides, pemphigus, psoriasis)
4. Gastrointestinal disorders (Crohn disease, ulcerative colitis)
5. Hematologic disorders (autoimmune hemolytic anemia, congenital hypoplastic anemia, erythroblastopenia,
thrombocytopenia)
6. Nonrheumatic inflammations (bursitis, tenosynovitis)
7. Neoplastic disease (leukemias, lymphomas, nasal polyps, cystic tumors)- prednisone
8. Neurologic diseases (tuberculous meningitis, multiple sclerosis, myasthenia gravis, carpal tunnel syndrome, back and
neck pain)
9. Neurotraumas (brain surgery, closed head injury, certain brain tumors, spinal cord injury)
10. Ophthalmic disorders (chorioretinitis, conjunctivitis, herpes zoster ophthalmicus, iridocyclitis, keratitis, optic neuritis)
11. Organ transplants (transplantation of liver, kidney, heart, and so forth)- prednisone, dexamethasone, methylprednisolone
12. Renal diseases (nephrotic syndrome, membranous glomerulonephritis)
13. Respiratory disorders (bronchial asthma, berylliosis, aspiration pneumonitis, symptomatic sarcoidosis, pulmonary
tuberculosis)- beclomethasone, fluticasone
14. Rheumatic disorders (ankylosing spondylitis, psoriatic arthritis, RA, gouty arthritis, OA)
-Principal desired effects of glucocorticoids
-Decrease inflammation
-Immunosuppression
-Antilymphocytic effects
-Decrease edema; inhibit free radical-induced neuronal damage
steroid synthesis
-Pharmacologists are manipulating the chemical side groups of these steroids to develop more effective and less toxic synthetic compounds.
-An example is the synthetic glucocorticoid dexamethasone, which is 25 times more potent than cortisol in reducing
inflammation but has a smaller tendency to cause sodium retention than the naturally occurring glucocorticoid
-Effects of glucose, protein, and lipid metabolism
-increase blood glucose and liver glycogen
-metabolic paradox accomplished by affecting
metabolism of glucose, fat, and protein
-cortisol facilitates the breakdown of muscle into
amino acids and lipids into free fatty acids
-cortisol also inhibits the uptake of glucose into
muscle and fat cells
-muscle breakdown is a primary problem with
patients taking glucocorticoids long term
-Clinical use of glucocorticoids
-Used in 2 primary situations:
-to evaluate and treat endocrine disorders
-to help resolve the symptoms of various
nonendocrine problems
-systemic preparations can be administered either
orally or parenterally to treat systemic disorders, such
as collagen diseases and adrenocortical insufficiency
-in more localized problems, can be applied directly
to a specific area using other preparations (topical,
ophthalmic)
-sometimes injected into a specific tissue or anatomic
space to treat a localized problem

15. Glucocorticoid Use in Endocrine Disorders

1. Administered systemically to help restore normal function in conditions of adrenal cortical hypofunction
1. Primary adrenal insufficiency (Addison disease)- due to deficient production (destruction of adrenal cortex)-
need glucocorticoid replacement
2. Secondary adrenal insufficiency- lack of adequate ACTH release from anterior pituitary- glucocorticoid replacement
2. Adrenalectomy or destruction of pituitary to resolve adrenal cortical hypersecretion (Cushing syndrome)
3. Use for diagnostic purposes to evaluate hormonal disorders
1. Exogenous glucocorticoids (dexamethasone) are potent inhibitors of ACTH secretion from anterior
pituitary. By suppressing the secretion of ACTH, glucocorticoids can help determine whether an
endocrine imbalance is influenced by ACTH secretion.
16. Adverse Effects
1. Adrenocortical suppression
1. Occurs because of the negative feedback effect of the administered glucocorticoids on the
hypothalamic-anterior pituitary system and the adrenal glands
2. Patient’s normal production of glucocorticoids is shut down by the exogenous hormones
3. Patients who have experienced complete suppression will not be able to immediately resume
production of glucocorticoids (medication must be withdrawn slowly by tapering the dose)
2. Drug-induced Cushing Syndrome- exhibit symptoms associated with adrenocortical hypersecretion (Cushing syndrome)
1. Symptoms of roundness and puffiness in the face, fat deposition and obesity in the trunk region,
muscle wasting in the extremities, hypertension, osteoporosis, increased body hair (hirsutism), and
glucose intolerance
3. Breakdown of Supporting Tissues
1. Glucocorticoids exert a general catabolic effect not only on muscle but also on bone, ligaments,
tendons, and skin- all subject to wasting from prolonged glucocorticoid use
2. Inhibit the genes responsible for production of collagen and other tissue components and by
increasing the expression of substances that promote breakdown of bone, muscle, etc.
3. Interfere with muscle protein synthesis by altering the muscle’s ability to retain and use amino
acidsàatrophy of skeletal muscle by increased rates of protein breakdown and decreased rates of
protein synthesis
1. In severe cases, glucocorticoids can induce a steroid myopathy that is characterized by
proximal muscle weakness, which can affect ambulation and functional abilities
4. Loss of bone strength- stimulate osteoclast-induced bone resorption while inhibiting osteoblast-
induced bone formation (suppress the production of substances that stimulate bone formation (IGF-
1), while increasing the expression of substances that promote bone loss (colony-stimulating factor-
I, nuclear factor k-B ligand)àloss of bone mineral content that can lead to osteoporosis and
osteonecrosis à fractures in the hips and vertebral bodies
4. Peptic ulcers may develop because of the breakdown of supporting proteins in the stomach wall or direct
mucosal irritation by the drugs
5. Increased susceptibility to infection often occurs because of the immunosuppressive effect
6. May retard growth in children, primarily through an inhibitory effect on the growth plates in developing bone
7. May cause glaucoma by impairing the normal drainage of aqueous fluid from the eye, and cataract
formation is associated with prolonged use
8. Mood changes and psychoses
9. Glucocorticoids with some mineralocorticoid-like activity can cause hypertension (Na and water retention)
10. Alter glucose metabolism, and people with DM will have an increased risk of hyperglycemia, insulin
resistance, and decreased control of BG levels
2. Describe clinical signs/symptoms and pharmacological management of thyroid disorders.
1. Hyperthyroidism (Thyrotoxicosis)
1. Types: Primary Hyperthyroidism: diffuse toxic goiter (Graves disease), thyroid adenoma/carcinoma
Secondary Hyperthyroidism: hyperthyroidism induced by excessive hypothalamic or pituitary stimulation
2. S/S: nervousness; weight loss; diarrhea; tachycardia; insomnia; increased appetite; heat intolerance;
oligomenorrhea; muscle wasting; goiter (enlargement of thyroid gland); exophthalmos (abnormal protrusion
of eyeball)
3. Pharmacological management: treat with drugs that attenuate the synthesis and effects of thyroid hormone
1. Antithyroid Agents: methimazole (Tapazole)
1. Directly inhibit thyroid hormone synthesis; control excessive thyroid hormone prior to
surgical removal of the thyroid
2. Work by inhibiting thyroid peroxidase (enzyme that oxidizes iodide to enable it to bond
to tyrosine residues) and by preventing the coupling of tyrosine residues within the
thyroglobulin molecule
2. Beta-Adrenergic Blockers: propranolol (Inderal)
1. Help suppress symptoms such as tachycardia, palpitations, fever, restlessness
2. Especially helpful in severe, acute exacerbations of thyrotoxicosis (thyroid storm)
3. Administered preoperatively to control symptoms until a more permanent means of
treating thyrotoxicosis (thyroidectomy) can be implemented
3. Radioactive Iodine

2. Hypothyroidism (Hypothyroxinemia)
1. Types: Primary Hypothyroidism: genetic deficiency of enzymes that synthesize thyroid hormones
Secondary Hypothyroidism: hypothyroidism induced by hypothalamic or pituitary deficiencies;
cretinism (childhood hypothyroidism); myxedema (adult hypothyroidism)
Other: hypothyroidism induced by peripheral insensitivity to thyroid hormones, inadequate hormone
transport, other causes
2. S/S: lethargy/slow cerebration; weight gain (adult hypothyroidism); constipation; bradycardia; sleepiness;
anorexia; cold intolerance; menorrhagia; weakness; dry, course skin; facial edema; (endemic goiter) due to
lack of dietary iodine
3. Pharmacological management: treated with thyroid hormone administration (replacement therapy)
1. Synthetic analogs such as preparations containing T4 (levothyroxine), T3 (liothyronine), or both
1. Combined regimen may result in greater improvements in mood, psychometric skills, and
perceived QOL in these individuals; important in children/infants with hypothyroidism who
need adequate amounts for normal activity and mental development; following
thyroidectomy or pharmacological ablation of the thyroid gland with radioactive iodine;
prevent and treat cancer of the thyroid gland and to prevent enlargement of the thyroid
gland (goiter) caused by other drugs such as lithium
3. Identify laboratory tests and imaging techniques that should be included in a chart review for a patient taking drugs
that affect bone mineralization.
1. Blood calcium levels: 8.5-10.4 mg/100mL (normal)
1. If plasma calcium levels fall to below 6 mg/100mL, tetanic muscle convulsions quickly ensue
2. Excess plasma calcium (> 12 mg/100mL) depresses nervous function, leading to sluggishness, lethargy,
and possibly coma
2. Bone Mass Density (DEXA Scan, CT scan, quantitative ultrasound, radiographic absorptiometry, x-ray reveals osteopenia)
1. Osteoporosis T score (-2.5 or lower); osteopenia T score (-1.0 to -2.5); normal (-1.0 or higher)
3. Excessive doses of Ca supplements may alter CV function, resulting in cardiac arrhythmias
1. PTs may help detect these arrhythmias while monitoring pulses or ECG recordings
4. FRAX tool- helps identify fracture risk
5. 25-hydroxyvitamin D plasma levels
6. Urinary calcium excretion test (urinary hydroxyproline, urinary deoxypyridinoline, N-telopeptide)
7. Biochemical markers of bone turnover (formation and resorption): Serum phosphate (3.5-4.5 mg/dL), creatinine (0.5-1.5
women; 0.6-1.2 men) alkaline phosphatase (44-147 IU- high value means bone disease), PTH, osteocalcin
8. methimazole (antithyroid agent)
-aplastic anemia (normal WBC differential value for neutrophils= 40-60%; decreased % (neutropenia)
2. levels of thyroid hormones in the blood and TSH
4. Explain mechanisms of action for specific drugs used to treat osteoporosis.
1. Calcitonin- effective and easy way to treat variety of conditions characterized by increased bone resorption
1. Mimics effects of endogenous calcitonin; increases bone formation in conditions such as Paget’s disease
and osteoporosis; also used to lower plasma calcium levels in hypercalcemic emergencies
2. Helps prevent bone loss in OA, postmenopausal osteoporosis, and glucocorticoid induced osteoporosis
1. Can reduce the risk of vertebral fractures but does not seem to be as effective as bisphosphonates
in reducing the risk
3. May have an analgesic effect on bone pain that complements the drug’s ability to promote bone healing,
especially in acute vertebral fractures
2. Calcitriol (Calcijex)- Vitamin D analog
1. Generally, enhance bone formation by increasing the absorption and retention of calcium and phosphate in
the body; useful in treating disorders caused by vitamin D deficiency, including hypocalcemia,
hypophosphatemia, rickets, and osteomalacia
2. Vitamin D is a precursor for several compounds that tend to promote bone mineralization, primarily by
increasing intestinal absorption of calcium and phosphate
1. Vitamin D analog is therefore used to increase blood calcium and phosphate levels and to enhance
bone mineralization in conditions such as osteodystrophy, rickets, or other situations where people
lack adequate amounts of vitamin D
1. Calcitriol can be combined with calcium supplements to help treat postmenopausal
osteoporosis and to treat bone loss caused by anti-inflammatory steroids (glucocorticoids)
3. Alendronate (Fosamax)- bisphosphonate
1. Appear to block excessive bone resorption and formation; used to normalize bone turnover in conditions
such as osteoporosis and Paget disease; prevent hypercalcemia resulting from excessive bone resorption in
certain forms of cancer
2. Compounds seem to absorb directly into calcium crystals in the bone and reduce bone resorption by
inhibiting osteoclast activity
3. Also inhibit abnormal bone formation in conditions such as heterotopic ossification and maintain bone
mineralization and prevent bone pain and fractures in cancers that metastasize to bone
4. Also help prevent and treat bone loss during prolonged administration of anti-inflammatory steroids
(glucocorticoids)
5. Primary treatment for osteoporosis, including osteoporosis due to estrogen loss in postmenopausal women
1. Can increase BMD and reduce risk of vertebral and nonvertebral fractures
 5. Explain the mechanisms of action for insulin and glucagon.
1. Insulin- primary effect is to lower blood glucose levels by facilitating entry of glucose into peripheral tissues
1. Effect of insulin on protein and fat
1. Insulin encourages protein synthesis in muscle cells by stimulating amino acid uptake, increasing
DNA/RNA activity related to protein synthesis, and inhibiting protein breakdown
2. Insulin stimulates the synthesis of fatty acids and triglycerides, increases the uptake of triglycerides
from the blood into adipose and muscle tissues, and inhibits the enzyme that breaks down stored
lipids (hormone sensitive lipase)
2. Effects of insulin on the liver: primary effect is to promote the sequestration of the glucose molecule and to
increase the storage of glucose in the form of hepatic glycogen
1. Since glucose is relatively permeable to hepatic cells, insulin stimulates the activity of the
glucokinase enzyme which phosphorylates glucose and subsequently traps the glucose molecule
in the hepatic cell
2. Insulin also increases the activity of enzymes that promote glycogen synthesis and inhibits the
enzymes that promote glycogen breakdown
3. Cellular mechanism- exerts its effects first by binding to a receptor (glycoprotein that is highly specific for
insulin) located on the surface membrane of target cells
1. Binding insulin to the alpha subunit of the insulin receptor causes the beta subunit to undergo
autophosphorylation—receptor adds phosphate groups to itself
2. When activated, the insulin receptor begins to add phosphate molecules to other large intracellular
proteins known as insulin receptor substrates (IRSs)
1. IRSs initiate changes in metabolic pathways that result in increased glucose uptake,
increased protein synthesis, and other changes in cell metabolism
2. Certain IRSs initiate the movement (translocation) of glucose transporters from
intracellular storage sites to the cell membrane of skeletal muscle cells and other
peripheral tissues
1. GLUT4 subtype, which is the glucose transporter in muscle and fat cells
3. By binding to the insulin receptor on the cell membrane, insulin ultimately causes GLUT4
proteins to travel to the cell membrane, where they can then promote the facilitated
diffusion of glucose into the cell
2. Glucagon- primary effect is to increase blood glucose to maintain normal BG levels and to prevent hypoglycemia
1. Glucagon produces a rapid increase in glycogen breakdown (glycogenolysis) in the liver, thus liberating
glucose into the blood stream from hepatic glycogen stores
2. It then stimulates a more prolonged increase in hepatic glucose production (gluconeogenesis), which
sustains BG levels even after hepatic glycogen has been depleted
3. Exerts its effect on liver cells by cAMP second messenger system
1. Glucagon binds to a specific receptor located on the hepatic cell membrane, which stimulates the
activity of the adenyl cyclase enzyme that transforms ATP into cAMP.
2. cAMP then acts as an intracellular second messenger that activates specific enzymes to increase
glycogen breakdown and stimulate gluconeogenesis

6. Interpret laboratory test values used for diagnosis and monitoring of diabetes
(ADA criteria).
7. Classify insulin preparations: rapid, short, intermediate, and long.

8. Plan or modify a patient's exercise schedule with consideration of time of insulin administration.
1. Know the site of insulin injection: try to avoid injecting a limb that you will be exercising immediately afterward (give
injection in abdomen or wait 1-2 hours). Check glucose: if below 80 then they probably need a snack
2. Know the time since the patients last meal: the best time for exercise is usually 30 min to 1 hour after meal
3. Know the glucose level prior to exercise: 80-100 OR 250-300, consult your physician
4. Monitor the glucose level periodically during exercise (depends on duration and intensity of the exercise)
5. Close clinical monitoring is necessary before, during, and after exercise
6. Avoid static weight lifting exercises (retinopathy precautions)
7. Rapid acting: Peak effect: 0.5-1.5 hrs; duration: 2-5 hrs (lispro- Humalog)
8. Short acting: Peak effect: 2-4 hrs; duration: 5-7 hrs (regular insulins- Humulin R)
9. Intermediate acting: peak effect: 6-12 hrs; duration: 18-28 hrs (isophane insulins- Humulin N)
10. Long acting: peak effect: 5-24 hrs; duration: 18-24 hrs (glargine- Lantus)

9. Describe clinical monitoring and management for adverse effects of antidiabetic drugs.
1. Primary adverse effect: hypoglycemia
1. Exogenous insulin may produce a dramatic fall in BG levels because insulin lowers BG
2. Hypoglycemia may occur during insulin therapy if the dose is higher than the patient needs
3. Missing a meal or receiving a delayed meal may also precipitate hypoglycemia
4. Strenuous physical activity may promote hypoglycemia during insulin therapy
1. Exercise produces an insulin-like effect, meaning it accelerates the movement of glucose out of the
bloodstream and into the peripheral tissues (skeletal muscle) where it is needed.
2. Combined effect of exercise and insulin may produce an exaggerated decrease in blood glucose,
thus leading to hypoglycemia
3. To avoid exercise-induced hypoglycemia, insulin dose should be decreased proportionally
depending on the type, intensity, and duration of the activity
1. Careful measurement of BG before and after exercise can help predict how much the
insulin should be adjusted
5. Initial symptoms: headache, fatigue, hunger, tachycardia, sweating, anxiety, confusion (BG 50-70 mg/dL)
1. In early stages, it can usually be reversed if the patient ingests foods containing glucose (soft drink,
fruit juice, glucose tablets, etc.) Administration of the equivalent of 15-20 g of D-glucose is
recommended to restore BG
6. Severe hypoglycemia may lead to loss of consciousness, convulsions, and death (BG 20-50 mg/dL)
2. Insulin allergy- any signs of allergic reaction such as pulmonary symptoms (tightness in throat and chest, wheezing,
cough, dyspnea) or skin reactions (rash, pruritus, urticaria) should be reported immediately
3. Heartburn, GI disturbances (N/V, diarrhea, flatulence, abdominal pain), lactic acidosis (confusion, lethargy, stupor,
shallow rapid breathing, tachycardia, especially during exercise), headache, dizziness, fatigue/weakness, back pain,
hepatic toxicity, edema, weight gain, fractures of the arm, hands, and feet in women (clinicians should be alerted for
any unexplained pain that might indicate fracture); hematologic abnormalities (leukopenia, agranulocytosis)
10. Classify oral antidiabetic medications by mechanism of action: sulfonylureas/meglitinides, biguanides,
thiazolidinediones, and alpha-glucosidase inhibitors.
1. Drugs that stimulate insulin secretion and supply: Sulfonylureas: glipizide (Glucotrol):
1. Increase insulin secretion from pancreatic beta cells; increased insulin release helps reduce BG by
increasing glucose storage in muscle and by inhibiting hepatic glucose production
2. Insulin Sensitizers: Biguanides: metformin (Glucophage)
1. act directly on the liver to decrease hepatic glucose production; also increase sensitivity of peripheral tissues
(muscle) to insulin
3. Insulin Sensitizers: Thiazolidinediones: rosiglitazone (Avandia):
1. act directly on the liver to decrease hepatic glucose production; also increase sensitivity of peripheral tissues
(muscle) to insulin
4. Other antidiabetics: Alpha-glucosidase inhibitors: acarbose (Precose):
1. Inhibit enzymes that break down sugars in the GI tractàhelps delay glucose absorption from the intestines,
thereby slowing the entry of glucose into the bloodstream and allowing time for the beta cells to respond to
hyperglycemia after a meal