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Questions and Answers
What symptom reported by the patient raises concern for a potential DVT?
What symptom reported by the patient raises concern for a potential DVT?
Which of the following medications is a muscle relaxant prescribed to the patient?
Which of the following medications is a muscle relaxant prescribed to the patient?
What lifestyle factor presents an increased risk for the development of a DVT in this patient?
What lifestyle factor presents an increased risk for the development of a DVT in this patient?
How should the physical therapist proceed after learning of the patient's increased headaches and calf tightness?
How should the physical therapist proceed after learning of the patient's increased headaches and calf tightness?
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What combination of factors contributes to the patient's elevated risk of developing a DVT?
What combination of factors contributes to the patient's elevated risk of developing a DVT?
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What is a primary function of insulin therapy in the management of diabetes mellitus?
What is a primary function of insulin therapy in the management of diabetes mellitus?
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What type of insulin is known to have the longest duration of action?
What type of insulin is known to have the longest duration of action?
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What is a common adverse drug reaction associated with sulfonylureas?
What is a common adverse drug reaction associated with sulfonylureas?
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Which type of insulin acts most rapidly after administration?
Which type of insulin acts most rapidly after administration?
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What is the primary action of biguanides, like Metformin?
What is the primary action of biguanides, like Metformin?
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What is a major concern when using insulin therapy in patients?
What is a major concern when using insulin therapy in patients?
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Which of the following insulin types is typically used for tighter blood glucose control?
Which of the following insulin types is typically used for tighter blood glucose control?
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GLP-1 agonists are used in the management of Type 2 diabetes because they do which of the following?
GLP-1 agonists are used in the management of Type 2 diabetes because they do which of the following?
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What is an important consideration in the administration of insulin?
What is an important consideration in the administration of insulin?
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What is the mechanism of action for alpha-glucosidase inhibitors?
What is the mechanism of action for alpha-glucosidase inhibitors?
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The most common side effects of GLP-1 agonists primarily include which of the following?
The most common side effects of GLP-1 agonists primarily include which of the following?
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Which class of oral antidiabetic drugs is known to decrease hepatic glucose production?
Which class of oral antidiabetic drugs is known to decrease hepatic glucose production?
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Which adverse effect is commonly associated with the use of DPP-4 inhibitors?
Which adverse effect is commonly associated with the use of DPP-4 inhibitors?
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What is a principle advantage of using metformin in diabetic management?
What is a principle advantage of using metformin in diabetic management?
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What is the immediate action to take when a patient exhibits symptoms of hypoglycemia during physical therapy?
What is the immediate action to take when a patient exhibits symptoms of hypoglycemia during physical therapy?
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Which medication is primarily used for hormone replacement therapy in hypothyroidism?
Which medication is primarily used for hormone replacement therapy in hypothyroidism?
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Which symptom indicates a possible overdose of hormone replacement therapy in a hypothyroid patient?
Which symptom indicates a possible overdose of hormone replacement therapy in a hypothyroid patient?
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What should you monitor in a patient taking medications for hyperparathyroidism?
What should you monitor in a patient taking medications for hyperparathyroidism?
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What is a significant adverse reaction of antithyroid agents used in hyperthyroidism treatment?
What is a significant adverse reaction of antithyroid agents used in hyperthyroidism treatment?
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What is the role of bisphosphonates in the management of hyperparathyroidism?
What is the role of bisphosphonates in the management of hyperparathyroidism?
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Which nutritional supplement is primarily used in the pharmacological management of hypoparathyroidism?
Which nutritional supplement is primarily used in the pharmacological management of hypoparathyroidism?
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What should be considered when treating a patient with hyperthyroidism and planning aquatic therapy?
What should be considered when treating a patient with hyperthyroidism and planning aquatic therapy?
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What is a common side effect of hormonal contraceptives that increase the risk of cardiovascular events?
What is a common side effect of hormonal contraceptives that increase the risk of cardiovascular events?
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Which of the following is NOT a symptom of vitamin D toxicity?
Which of the following is NOT a symptom of vitamin D toxicity?
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What is the primary purpose of estrogen replacement therapy in postmenopausal women?
What is the primary purpose of estrogen replacement therapy in postmenopausal women?
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What is the main effect of anabolic steroids when abused?
What is the main effect of anabolic steroids when abused?
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Which hormone therapy is used to feminize transgender females?
Which hormone therapy is used to feminize transgender females?
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What is a recommended rehabilitation consideration for a patient on calcium and vitamin D supplementation for hypoparathyroidism?
What is a recommended rehabilitation consideration for a patient on calcium and vitamin D supplementation for hypoparathyroidism?
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Study Notes
Endocrine Pharmacology
- Linda B. Horn, PT, DScPT, MHS, FNAP is a Fellow of the National Academies of Practice, Board Certified in Geriatric and Neurologic Physical Therapy, Advanced Vestibular Physical Therapist, and Certified Exercise Expert for Aging Adults.
- The course is DPTE 513 BS II, 2024.
Behavioral Objectives
- Describe the pharmacokinetics and pharmacodynamics of drugs used to treat endocrine disorders.
- Describe adverse drug reactions (ADRs) that can occur with drugs used to treat endocrine disorders.
- Explain the impact of these drugs on rehabilitation.
Endocrine Pharmacology (Replacement)
- Replacement: Increasing hormonal effect.
- Treat excessive endocrine function.
- Regulate/manipulate normal endocrine function.
Insulin Therapy for Diabetes Mellitus
- Large polypeptide; parenteral administration (too large to cross GI wall, usually subcutaneous injection, may be delivered IV in emergencies, insulin pumps).
- Animal sources (pork), biosynthetically produced human insulin.
- Increased glucose entry and storage in tissues (muscle & liver). Increased protein synthesis and lipid storage.
Types of Insulin
- Regular insulin: Synthetic or pork; absorption is slower than endogenous insulin released from the pancreatic beta cells. Examples: Human (Humulin R, Novolin R), Animal (Regular Iletin II).
- Rapid-acting insulin: Biosynthetic, slightly different from human insulin to allow rapid absorption. Examples: Human (Aspart [NovoLog], Glulisine [Apidra], Lispro [Humalog]).
- Intermediate-acting insulin: Absorbed slower and have a prolonged effect. Created by adding acetate buffers & zinc. Examples: Human (Humulin L, Novolin L) and Animal (Lente Insulin, Lente Insulin II, NPH Insulin, NPH Purified Insulin, NPH Ileutin II).
- Long-acting insulin: Absorbed slower and has a prolonged effect. Used when less stringent control of blood sugar is needed (e.g., person controlling condition with diet & weight control). May be used if a person has problems with overnight hypoglycemia. Examples: Glargine (Lantus), Extended insulin zinc (Humulin U), Ultralente.
- Combinations: Intermediate-acting + rapid-acting insulin to optimize blood sugar control. Ratio will depend on individual needs (e.g., 50:50, 70:30, 75:25). Example: Humalog 75/25 (75% insulin lispro protamine [intermediate-acting] and insulin lispro [rapid-acting]).
Insulin
- Table of insulin types, peak effect, and duration.
Intensive Insulin Therapy
- Maintain blood glucose in the normal physiologic range.
- Frequent monitoring of blood glucose and self-administration of insulin (3 or more doses during the day) to meet patient needs.
- Decreases long-term complications due to "tighter control."
Insulin Therapy ADR
- Immunologic reactions (allergic reaction, rash, wheezing, bronchoconstriction, etc.)—usually associated with animal forms of insulin.
- Hypoglycemia—reasons include dose greater than patient's needs, missed or delayed meals, exercise.
- Initial signs & symptoms: headache, fatigue, hunger, tachycardia, sweaty/clammy, pale, anxiety, and confusion.
- Later signs & symptoms: Loss of consciousness, seizures, death.
Considerations for Insulin Therapy
- Needs to be refrigerated.
- Sterile syringes.
- Accurately measure the dose and fill the syringe (pre-filled syringes as alternative).
- Proper administration site (rotate sites: abdomen, upper thighs, upper arms, back, buttocks).
- Glucose monitoring.
- Dose may be set at certain times of the day.
- Sliding scale based on current blood glucose levels.
Oral Antidiabetic Drugs
- Control blood glucose levels for Type 2 DM.
- Increase the release of insulin from pancreatic beta cells.
- Increase the sensitivity of peripheral tissues to insulin.
- Types: Sulfonylureas, Biguanides, Alpha-glucosidase inhibitors, Thiazolidinediones, Benzoic acid derivatives.
Sulfonylureas
- Action:↑ insulin release;↓ hepatic glucose production.
- Variable efficacy and effects decrease with time.
- Examples: Chlorpropamide (Diabinese), Glipizide (Glucotrol), Glyburide (DiaBeta, Micronase), Tolazamide (Tolinase), Tolbutamide (Orinase)
- ADR: Hypoglycemia (most common), GI disturbances, headaches.
Biguanides
- Action: ↓ hepatic glucose production; ↑ tissue sensitivity to insulin.
- Example: Metformin (Glucophage).
- ADR: GI disturbances, lactic acidosis (rare but can be fatal).
Comparison of Sulfonylurea & Metformin
- Study of veterans (≥18 y/o) receiving regular care from the VA.
- Sulfonylurea use associated with a 21% increase in cardiovascular events (stroke, MI) and deaths.
- Confirms use of metformin as the first-line drug for diabetes treatment.
- Strengthens the evidence about the cardiovascular benefits of metformin.
Alpha-Glucosidase Inhibitors
- Action: Inhibit glucose absorption from GI tract; Inhibit enzymes that break down sugars in the GI tract; blood stream slows the entry of glucose into the bloodstream.
- Examples: Acarbose (Precose), Miglitol (Glyset).
- ADR: GI disturbances.
Thiazolidinediones
- Action: ↓ hepatic glucose production; ↑ tissue sensitivity to insulin.
- Examples: Pioglitazone (Actos), Rosiglitazone (Avandia).
- ADR: Headaches, dizziness, fatigue/weakness, back pain, hepatic toxicity (rare).
Benzoic Acids
- Action: ↑ insulin release (similar to sulfonylureas).
- Examples: Repaglinide (Prandin), Nateglinide (Starlix).
- ADR: Hypoglycemia, bronchitis, upper respiratory tract infections, joint & back pain, GI disturbances, headaches.
Managing Hypoglycemia
- Glucagon—used to treat hypoglycemia associated with insulin or oral hypoglycemic agents. Mobilizes glucose release from the liver. Effective administration (IV, IM, subcutaneous, tablets).
- ADR: nausea, vomiting, allergic reaction (skin rash, difficulty breathing). Should reverse symptoms within 10 minutes.
Other Drugs Used to Manage Type 2 DM
- Glucagon-like Peptide 1 (GLP-1) agonists:
- GLP-1 is a hormone released from the GI tract after eating.
- Stimulates insulin release from pancreas.
- Decreases glucagon release; delays absorption of food; reduces appetite.
- Manage blood sugar (BS), lower A1C, weight loss.
- Should not be used with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia. Not recommended for pancreatitis.
- Examples: Exenatide (Byetta), Tirzepatide (Mounjaro), Semaglutide (Ozempic, Wegovy, Rybelsus).
- Side effects: GI symptoms (nausea, vomiting, diarrhea), hypoglycemia.
- Dipeptidyl peptidase-4 (DPP-4) inhibitors:
- Inhibits enzyme (DPP-4) that breaks down GLP-1.
- Prolongs the effects of GLP-1.
- Example: Sitagliptin (Januvia), Vildagliptin (Galvus).
- Immunosuppressants:
- Used in Type 1 DM.
- Limits beta cell destruction; decreases the need for exogenous insulin.
- May decrease the severity of the disease.
- Examples: Cyclosporine, Azathioprine, Cyclophosphamide, Methotrexate, Glucocorticoids.
- ADR: severe side effects at high doses and prolonged use.
Rehab Considerations for Patients Taking Drugs for DM
- Have glucose-containing foods readily available for hypoglycemia.
- Can patient (or another person) self-administer insulin correctly?
- Insulin absorption can be affected by physical agents (heat, cold), massage, and exercise.
- Patient education on diet, exercise, and signs & symptoms of low blood sugar. Ask about most recent blood sugar level.
Case #1
- 75-year-old patient receiving outpatient physical therapy for gait and balance impairments.
- Comes to therapy at 9 am, 2x/week.
- Reports shaky feeling, headache, pulse 100 bpm, sweating, and pale.
- History of DM & hypertension.
- Medications: Humalog 75/25, Furosemide, Atenolol.
- Considerations: Possible hypoglycemia, need to monitor vital signs, communicate with physician.
- Next step: Monitor VS; administer juice, soda, etc, to increase blood sugar; contact physician if patient doesn't respond. Ask about blood sugar levels, timing of insulin, and meals eaten.
Pharmacological Management of Hyperthyroidism (Thyrotoxicosis)
- Antithyroid agents: Inhibit synthesis of thyroid hormones (temporary measure). Examples: Propylthiouracil (Propyl-Thyracil), Methimazole (Tapazole).
- ADR: skin rash, itching, agranulocytosis (↓ WBC), aplastic anemia (↓ RBC). Excessive inhibition can cause hypothyroidism-like symptoms.
- Beta blockers: Used to treat symptoms of tachycardia, palpitations, etc.
- Iodide: Large doses cause a rapid decrease in thyroid function; effects diminish ≈ 2 weeks of use. May be used prior to thyroidectomy. ADR: severe hypersensitivity (allergic) response.
- Radioactive iodine: Selectively destroys thyroid tissue (follicle). Grave's disease requires ablation of the thyroid gland, necessitating thyroid replacement therapy.
Pharmacological Management of Hypothyroidism (Hypothyroxinemia)
- Hormone replacement therapy (debate whether to replace T4 only or both T3 & T4).
- Used after thyroidectomy, pharmacologic ablation, or for other hypothyroid conditions.
- Examples: Levothyroxine (T4), Liothyronine (T3), Liotix & Thyroid (T3 and T4)
- Primary ADR related to overdose mimics hyperthyroidism symptoms.
Rehab Considerations for Patients Taking Drugs for Thyroid Disorders
- Monitor patient for signs and symptoms related to dosing problems.
- Too little hormone replacement mimics hypothyroidism.
- Too much hormone replacement can mimic hyperthyroidism.
- Differentiate disease process from drug-related ADRs.
- Watch for treatment interactions (hypo- and hyper- thyroid).
- Monitor vital signs.
Management of Hyperparathyroidism
- Hyperparathyroidism: Often managed surgically.
- Alternative pharmacological management of hypercalcemia:
- Biphosphonates (e.g., alendronate, ibandronate, risedronate) reduce bone absorption by inhibiting osteoclasts. ADRs: nausea, diarrhea, esophagitis (reflux).
- Calcitonin: Synthetic hormone mimicking endogenous hormone to decrease blood calcium levels and promote bone mineralization. Administered by injection (IM, subcutaneous) or nasal spray.
Pharmacological Management of Hypoparathyroidism
- Calcium supplements: Used to ensure adequate calcium for physiologic processes and bone formation. Dose should meet individual needs. Avoid hypercalcemia. Examples: calcium carbonate, calcium citrate.
- Vitamin D: Fat-soluble vitamin used to increase blood calcium and phosphate levels, enhancing bone mineralization and intestinal absorption.
- Signs of vitamin D toxicity: headache, increased thirst, decreased appetite, metallic taste, fatigue, GI disturbances, hypercalcemia, hypertension, cardiac arrhythmias, renal failure, mood changes, seizures, death.
Rehab Considerations for Patients Taking Drugs for Parathyroid Disorders
- Monitor patients for signs and symptoms related to toxicity.
- Weight-bearing activities to stimulate bone formation.
- Avoid stress to bones (avoid spinal flexion and rotation exercises, torque).
- UV light promotes endogenous Vitamin D synthesis and bone formation.
- Monitor vital signs.
Male & Female Hormones
- Male: Androgens (testosterone). Clinical use: replacement therapy (s/p orchiectomy, decreased hormone levels, delayed puberty, breast cancer, anemia, match gender identity).
- Female: Estrogens (estradiol, etc.) and progestins (progesterone). Clinical use: replacement therapy, regulation of menstrual cycle and endometriosis, contraception, cancer, match gender identity.
Androgens
- Testosterone replacement: Small doses to counteract aging effects in men.
- Benefits: Body composition, strength, bone mineralization, glucose metabolism, mood, and libido.
- Risks: Increased prostate growth and possible increased risk of prostate cancer.
Androgen Abuse
- Anabolic steroids: Used to increase muscle size and strength.
- Often used together ("stacking").
- Adverse effects: Liver damage, cardiovascular disease, affected bone metabolism, accelerated closure of epiphyseal plates in children, avascular necrosis of femoral heads, aggression and mood swings, testicular atrophy, and impaired sperm production.
Hormonal Contraceptives
- Different formulations: estrogen & progesterone combinations, progesterone only.
- Administration: Oral, injections, transdermal patches, vaginal ring.
- Risks: Cardiovascular (MI, stroke, clots), cancer (uterine, breast). Factors that increase risks include smoking, personal or family history, advanced age, and prolonged use.
Estrogen Replacement Therapy
- Relieve menopausal symptoms, prevent/treat osteoporosis, improve cardiovascular health, possible protection from cognitive decline.
- Risks include cancer, stroke, and DVT.
- Selective Estrogen Receptor Modulators (SERMs): Activate estrogen receptors on bone, block them on breast and uterus. Improve bone mineralization and cardiovascular function. Examples: Tamoxifen (Nolvadex), Raloxifene (Evista).
Hormone Therapy for Persons with Gender Dysphoria
- Transgender Males: Exogenous testosterone to induce virilization and suppress feminizing characteristics.
- Transgender Females: Anti-androgens (e.g., spironolactone) to suppress masculinizing characteristics and exogenous estrogen to feminize. Another option: Gonadotropin-releasing hormone (Gn-RH) analogues.
Rehab Considerations for Patients Taking Male & Female Hormones
- Monitor patient for signs and symptoms related to dosing.
- Monitor for signs of androgen abuse.
- Monitor vital signs.
Case #2
- 25-year-old patient receiving outpatient physical therapy for a whiplash injury.
- History of smoking, drinking socially.
- Medications: Flexeril, oral contraceptive (estrogen & progesterone), acetaminophen.
- Patient reports increased headaches, dull ache and tightness in the right calf.
- Concerns: Possible DVT (risk factors: oral contraceptive, smoking).
- Next steps: Notify physician.
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