Endocrine Pharmacology Notes PDF

Endocrine Pharmacology Linda B. Horn, PT, DScPT, MHS, FNAP Fellow, National Academies of Practice Board Certified Clinical Specialist in Geriatric and Neurologic Physical Therapy Advanced Vestibular Physical Therapist Certification...

Endocrine Pharmacology Linda B. Horn, PT, DScPT, MHS, FNAP Fellow, National Academies of Practice Board Certified Clinical Specialist in Geriatric and Neurologic Physical Therapy Advanced Vestibular Physical Therapist Certification Certified Exercise Expert for Aging Adults DPTE 513 BS II 2024  Behavioral Objectives Describe the pharmacokinetics & pharmacodynamics of drugs used to treat endocrine disorders Describe the adverse drug reactions (ADR) that may occur with drugs used to treat endocrine disorders Explain the impact of these drugs on rehabilitation Endocrine Pharmacology Replacement Increase 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 Types – Animal sources (pork) – Biosynthetically produced human insulin Effects – Increased glucose entry & storage in tissues such as muscle & liver – Increases protein synthesis  Types of Insulin Regular insulin – Synthetic or pork – Absorption slower than endogenous insulin released from the pancreatic beta cells – Examples Human – Humulin R, Novolin R Animal – Regular Iletin II  Types of Insulin Rapid-acting insulin – Biosynthetic insulin that is slightly different than human insulin to allow rapid absorption – Examples Human – Aspart (NovoLog) – Glulisine (Apidra) – Lispro (Humalog)  Types of Insulin Intermediate-acting insulin – Absorbed slower and have a prolonged effect – Created by adding other agents to insulin Add acetate buffers & zinc – Lente insulins » Human: Humulin L, Novolin L » Animal: Lente Insulin, Lente Insulin II Add protamine and zinc – NPH insulins » Human: Humulin H, Novolin H » Animal: NPH Insulin, NPH Purified Insulin, NPH Ileutin II  Types of Insulin Long-acting insulin – Absorbed slower and has a prolonged effect Used when less stringent control of blood sugar is needed such as person controlling condition with diet & weight control May be used if person has problems with hypoglycemia overnight – Biosynthetic – Examples Glargine (Lantus) Extended insulin zinc (Humulin U) Ultralente  Types of Insulin Combinations – To provide optimal control of blood sugar Intermediate-acting + rapid-acting – Ratio will vary depending on needs of person » 50:50, 70:30, 75:25, etc – Example » 75% insulin lispro protamine (intermediate- acting) and insulin lispro (rapid-acting) = Humalog 75/25  Insulin TYPE OF INSULIN PEAK EFFECT DURATION Rapid-acting 0.5-1.5 hrs < 5 hrs Regular 1.4-4.0 hrs 5-8 hrs Intermediate –acting 6-12 hrs 18-24 hrs Long-acting 14-24 hrs 18-36 hrs * Times will vary from person to person  Intensive Insulin Therapy Goal: maintain blood glucose in the normal physiologic range Frequent monitoring of blood glucose level and self-administration of insulin (3 or more doses during day) to meet patient’s needs Decreases long-term complications due to “tighter control”  Insulin Therapy ADR Immunologic reaction – Allergic reaction (rash, wheezing, bronchoconstriction, etc) – Usually associated with animal forms of insulin Hypoglycemia – Reasons Dose greater than patient’s needs Missed or delayed meal Exercise – accelerates the movement of glucose out of bloodstream into skeletal muscle  Hypoglycemia Initial signs & symptoms of hypoglycemia – Headache – Fatigue – Hunger – Tachycardia – Sweaty/Clammy – Pale – Anxiety – Confusion  Hypoglycemia Later signs & symptoms of hypoglycemia – Loss of consciousness – Seizures – Death  Considerations for Insulin Therapy Insulin needs to be refrigerated Need sterile syringes Accurately measure dose & fill syringe – Other option: pre-filled syringes Use proper administration site Administer correctly – Rotate sites (abdomen, upper thighs, upper arms, back, buttocks) Glucose monitoring Dose – May be set dose at certain times of the day – Sliding scale based on current blood glucose level  Oral Antidiabetic Drugs Control blood glucose levels in Type 2 DM Action – Increase release of insulin from pancreatic beta cells – Increase sensitivity of peripheral tissues to insulin Types – Sulfonylureas – Biguanides – Alpha-glucosidase inhibitors – Thiazolidinediones – Benzoic acid derivatives  Sulfonylureas Action – ↑ insulin release – ↓ hepatic glucose production Liver reduces amount of glucose produced as it senses more insulin coming from the pancreas Variable efficacy & effects decrease with time Examples – Chlorpropamide (Diabinese) – Glipizide (Glucotrol) – Glyburide (DiaBeta, Micronase) – Tolazamide (Tolinase) – Tolbutamide (Orinase) ADR – Hypoglycemia (most common) – GI disturbances – Headache  Biguanides Action – ↓ hepatic glucose production – ↑ tissue sensitivity to insulin Examples – Metformin (Glucophage) ADR – GI disturbances – Lactic acidosis (rare, but can be fatal)  Comparison of Sulfonylurea & Metformin Study population – veterans > 18 y/o who received regular medical care from the VA Sulfonylurea use associated with 21% increase in cardiovascular events (stroke, MI) & deaths Confirms use of metformin as first-line drug for treatment of diabetes Strengthens the evidence about the cardiovascular benefits of metformin Roumie, 2012 Alpha-Glucosidase Inhibitors Action – Inhibit glucose absorption from the GI tract Inhibit enzymes that break down sugars in the GI tract which slows the entry of glucose into the bloodstream Examples – Acarbose (Precose) – Miglitol (Glyset) ADR – GI disturbances  Thiazolidinediones Action (similar to biguanides) – ↓ hepatic glucose production – ↑ tissue sensitivity to insulin Examples – Pioglitazone (Actos) – Rosiglitazone (Avandia) ADR – Headache – Dizziness – Fatigue/weakness – Back pain – Hepatic toxicity (rare)  Benzoic Acids Action (similar to sulfonylureas) – ↑ insulin release Examples – Repaglinide (Prandin) – Nateglinide (Starlix) ADR – Hypoglycemia – Bronchitis – Upper respiratory tract infections – Joint & back pain – GI disturbances – Headache  Managing Hypogycemia Glucagon – Used to treat hypoglycemia associated with insulin or oral hypoglycemic agents – Mobilizes release of glucose from liver Sufficient glycogen needed in the liver to be effective – Administration IV, IM, subcutaneous, tablets – Should reverse symptoms within 10 min – ADR: nausea, vomiting, allergic reaction (skin rash, difficulty breathing) Other Drugs Used to Manage Type 2 DM Glucagon-like Peptide 1 (GLP-1) agonists – GLP-1 is a hormone that is normally released from the GI tract after eating a meal Stimulates insulin release from pancreas Decreases glucagon release, delays absorption of food, & reduces appetite – GLP-1 agonists Manage BS Lower A1C Weight loss – Should not use GLP-1 agonists with a personal or family history of medullary thyroid cancer ormultiple endocrine neoplasia – Not recommended with h/o pancreatitis  GLP-1 Agonists Exenatide (Byetta) – Injected before morning and evening meals to prevent BS spikes Tirzepatide (Mounjaro) – Once weekly injection Semaglutide – Injection (Ozempic, Wegovy) Once weekly injection Only Wegovy approved for weight loss – Rybelsus Lower BS Tablet  Side Effects of GLP-1 Agonists GI symptoms – most common – Nausea – Vomiting – Diarrhea Hypoglycemia  Other Drugs Used to Manage DM Dipeptidyl peptidase-4 (DPP-4) inhibitors – Inhibits the enzyme (DPP-4) that breaks down GLP-1 to prolong the effects of GLP-1 – Example: Sitagliptin (Januvia), Vildagliptin (Galvus)  Other Drugs Used to Manage DM Immunosuppressants – Used in Type 1 DM – Limits beta cell destruction & decreases need for exogenous insulin – Some evidence that some of these agents may decrease the severity of the disease – Example: Cyclosporine, Azathioprine, Cyclophosphamide, Methotrexate, Glucocorticoids – ADR: severe side effects when used at high doses for long periods of time  Rehab Considerations for Patients Taking Drugs for DM Have foods containing glucose readily available in case of hypoglycemia (juice, non-diet sodas, glucose tablets, etc) Can patient or other person self-administer insulin appropriately? Insulin absorption affected by – Physical agents (heat, cold) – Massage – Exercise Patient education – Diet – Exercise – Signs & symptoms of low blood sugar Ask patient about most recent blood sugar level  CASE #1 A 75 y/o patient is receiving outpatient physical therapy for gait & balance impairments. They come to PT at 9 am 2x/wk. They c/o feeling shaky and have a headache. Their pulse is 100 bpm. They are sweating and pale. PMH includes a h/o DM & hypertension. Meds: Humalog 75/25, Furosemide, Atenolol. – What are considerations when working with this patient? – What is your next step? – Other considerations  CASE #1 A 75 y/o patient is receiving outpatient physical therapy for gait & balance impairments. They come to PT at 9 am 2x/wk. They c/o feeling shaky and have a headache. Their pulse is 100 bpm. They are sweating and pale. PMH includes a h/o DM & hypertension. Meds: Humalog 75/25, Furosemide, Atenolol. – What are considerations when working with this patient? Monitor VS Patient is probably experiencing hypoglycemia – What is your next step? Administer juice, soda, etc to increase blood sugar Contact physician if patient doesn’t respond – Other considerations Ask patient about blood sugar levels, timing of insulin, meal 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 will cause symptoms resembling hypothyroidism Beta blockers – Used to treat symptoms of tachycardia, palpitations, etc  Pharmacological Management of Hyperthyroidism (Thyrotoxicosis) Iodide – Large doses to 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 – Radioactive isotope selectively destroys thyroid tissue (follicle) – Grave’s Disease – Ablates thyroid gland & need to have thyroid replacement therapy  Pharmacological Management of Hypothyroidism (Hypothyroxinemia) Hormone replacement therapy – Debate about whether to replace T4 only or both T3 & T4 – Used after thyroidectomy, pharmacologic ablation, treatment of goiter, other hypothyroidism – Examples Levothyroxine (Levothroid, Synthroid, others): T4 Liothyronine (Cytomel): T3 Liotix (Thyrolar) & Thyroid (Armour Thyroid, others): T 3 and T4 – Primary ADR related to overdose with symptoms similar to hyperthyroidism  Rehab Considerations for Patients Taking Drugs Thyroid Disorders Monitor patient for signs & symptoms related to dosing problems – Too little hormone replacement: mimics hypothyroidism – Too much hormone replacement: mimics hyperthyroidism Differentiate between disease process & ADR due to drug therapy Watch for treatment interactions – Patient with hyperthyroidism may not be a good candidate for aquatic therapy in warm water due to heat intolerance – Patient with hypothyroidism may have difficulty doing performing aerobic exercise due to lethargy & sleepiness Monitor vital signs  Management of Hyperparathyroidism Hyperparathyroidism usually managed with surgical resection Alternative pharmacological management of hypercalcemia – Biphosphonates (AKA diphosphonates) Reduce bone absorption by inhibiting osteoclast activity Used to treat osteoporosis as well as other diseases with excessive bone turnover Examples: alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel) ADR: nausea, diarrhea, esophagitis (reflux into the esophagus causing irritation) – Patient instructed to remain upright x30 min after taking these drugs  Management of Hyperparathyroidism Alternative pharmacological management of hypercalcemia – Calcitonin Synthetic hormone mimics endogenous hormone to ↓ blood calcium levels and promote bone mineralization Administered by injection (IM or subcutaneous) or nasal spray Example: Cibacalin, Calcimar, Miacalcin (nasal spray) ADR: injection site redness & swelling, GI (stomach pain, nausea, vomiting, diarrhea), loss of appetite, flushing/redness in head, hands, & feet  Pharmacological Management of Hypoparathyroidism Calcium Supplements – Used to ensure adequate calcium is present for physiologic processes & encourage bone formation – Dose: to meet individual needs – Want to avoid hypercalcemia – Examples: calcium carbonate (Os-Cal 500, Tums, etc), calcium citrate (Citracal), others  Pharmacological Management of Hypoparathyroidism Signs of Hypercalcemia – Constipation – Drowsiness – Fatigue – Headache – Confusion – Irritability – Cardiac arrhythmias – Hypertension – Nausea & vomiting – Skin rash – Pain in bones & muscle  Pharmacological Management of Hypoparathyroidism Vitamin D – Fat-soluble vitamin – Used to ↑ blood calcium & phosphate levels to enhance bone mineralization ↓ renal excretion of calcium & phosphate ↑ intestinal absorption of calcium & phosphate  Pharmacological Management of Hypoparathyroidism Signs of Vitamin D toxicity – Headache – Increased thirst – Decreased appetite – Metallic taste – Fatigue – GI disturbances (nausea, vomiting, constipation, diarrhea) – Hypercalcemia – Hypertension – Cardiac arrhythmias – Renal failure – Mood changes – Seizures – Death due to cardiac & renal complications  Rehab Considerations for Patients Taking Drugs for Parathyroid Disorders Monitor patient for signs & symptoms related to toxicity Weight bearing activities to stimulate bone formation Avoid stress to bones that may be weak – Osteoporosis – avoid spinal flexion & rotation exercises; avoid torque across weakened areas UV light promotes endogenous Vitamin D synthesis & bone formation  Male & Female Hormones Male Female Androgens (Testosterone) Estrogens (Estradiol, etc) Clinical use Replacement Replacement therapy Progestins (Progesterone, etc) s/p orchiectomy (removal of Clinical use testes) Replacement therapy Decreased hormone levels Regulation of menstrual cycle & Delayed puberty endometriosis Breast cancer Cancer Anemia Contraception Match gender identity Match gender identity  Androgens Testosterone replacement – Small doses to counteract effects of aging in men Benefits – Body composition – Strength – Bone mineralization – Glucose metabolism – Mood – Libido Risks – Increase prostate growth – Possible increase of prostate cancer risk  Androgen Abuse Anabolic steroids – Used to ↑ muscle size & strength – Use several anabolic steroids together Known as “stacking” – ADR associated with high doses of anabolic steroids Liver damage Cardiovascular disease Affect bone metabolism – Accelerate closure of epiphyseal plates leading to impaired skeletal growth in children – Avascular necrosis of femoral heads Aggression & severe mood swings Testicular atrophy & impaired sperm production No problems if anabolic steroids taken at physiologic doses  Hormonal Contraceptives Different Oral contraceptive formulations risks – Estrogen & – Cardiovascular (MI, Progesterone stroke, clots) combinations – Cancer (uterine, – Progesterone only breast) Administration Factors that ↑ risk – Oral – Smoking – Injections – Personal or family – Transdermal patches history – Vaginal ring – Advanced age – Prolonged use  Estrogen Replacement Therapy Relieve menopausal symptoms Prevent & treat menopausal osteoporosis Improved cardiovascular health – Has been challenged by the results of several studies Protection from cognitive decline – No conclusive evidence; some studies show increased cognitive decline in older post-menopausal women Risks – Cancer – Stroke – DVT  Estrogen Replacement Therapy Needs to be evaluated on an individual basis – Benefit vs risk Selective Estrogen Receptor Modulators (SERMs) – Activates estrogen receptors on bone and block estrogen receptors on breast & uterus – Improve bone mineralization & 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 to suppress masculinizing characteristics (Spironolactone [Aldactone]) – Exogenous estrogen to feminize patients – Another option: gonadotropin-releasing hormone (Gn-RH) analogs  Rehab Considerations for Patients Taking Male & Female Hormones Monitor patient for signs & symptoms related to dosing Monitor for signs of androgen abuse Monitor vital signs  CASE #2 A 25 y/o patient is receiving outpatient physical therapy for a whiplash injury suffered during a motor vehicle accident. They smoke ½ PPD (pack per day) & drink socially (3-4x/mo). Meds: Flexeril (muscle relaxant), oral contraceptive with Estrogen & Progesterone, Acetaminophen as needed. – Today, the patient reports an increase in headaches. Additional questions reveal c/o a dull ache & tightness in the right calf. What are your concerns & why? – How do you proceed?  CASE #2 A 25 y/o patient is receiving outpatient physical therapy for a whiplash injury suffered during a motor vehicle accident. They have been receiving PT x 2 wks and had reported improvement in pain & ROM. They smoke ½ PPD (pack per day) & drinks socially (3-4x/mo). Meds: Flexeril (muscle relaxant), oral contraceptive with Estrogen & Progesterone, Acetaminophen as needed. – Today, the patient reports an increase in headaches. Additional questions reveal c/o a dull ache & tightness in the right calf. What are your concerns & why? Concern: Patient may have a DVT Why? – Risk factors: oral contraceptive & smoking – How do you proceed? Notify physician  References Ciccone, C. D. (2022). Pharmacology in Rehabilitation (5th ed.). Philadelphia: F. A. Davis. Roumie, C. L, et al. (2012). Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus. Ann Intern Med, 157, 601-610.