Essentials of Pharmacology: Endocrine System Drugs Notes

Overview of the Endocrine System

  • Definition of the Endocrine System: A body control system that exerts its effects slowly and over a longer period of time.

  • Hormones: These are chemical messengers that have specialized functions in regulating the activities of specific cells or organs. They travel through the bloodstream to reach their designated targets.

  • Endocrine System Drugs: This category includes natural hormones secreted by the ductless glands as well as synthetic substitutes designed to mimic or block their actions.

Pituitary Hormones

  • Characteristics and Location of the Pituitary Gland:     * It is located at the base of the brain.     * It is known for regulating the function of other endocrine glands.

  • Secreted Hormones:     * Somatotropin: Also known as human growth hormone (HGH).     * Adrenocorticotropic hormone (ACTH).     * Thyroid-stimulating hormone (TSH).     * Gonadotropic hormones: These include Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Luteotropic Hormone (LTH).

Adrenal Corticosteroids

  • Definition: Hormones secreted by the adrenal glands that act on the immune system to suppress responses to infection or trauma. They are utilized to relieve inflammation, reduce swelling, and suppress symptoms in acute conditions.

  • Categories of Use:     * Replacement Therapy: For example, in the treatment of Addison’s disease.     * Anti-inflammatory and Immunosuppressant Agents: Used to manage immune-mediated conditions.

  • Specific Conditions Treated:     * Allergic reactions.     * Acute flare-ups of rheumatic or collagen disorders.     * Acute flare-ups of severe skin conditions.     * Acute respiratory disorders.     * Long-term prevention of symptoms in severe persistent asthma.     * Malignancies.     * Cerebral edema.     * Organ transplant.     * Life-threatening shock.     * Acute flare-ups of ulcerative colitis.

  • General Therapy Principle: Corticosteroid therapy is not curative; it is used as supportive therapy in conjunction with other medications.

  • Potential Side Effects:     * Adrenocortical insufficiency and adrenocortical atrophy.     * Delayed wound healing and increased susceptibility to infection.     * Muscle pain or weakness.     * Osteoporosis with fractures, particularly noted in older adult females.     * Stunting of growth in children.    

  •  * Cushing’s Syndrome: Manifestations include obesity of the trunk, ‐moon face,‐ acne, hirsutism, amenorrhea, and hyperglycemia.     * Gastric or esophageal irritation, ulceration, or hemorrhage.     * CNS Effects: Headache, vertigo, insomnia, euphoria, psychosis, or anxiety.     * Petechiae, easy bruising, skin thinning, and tearing.     * Increased blood sugar or fluctuating blood sugar levels.

  • Cautions and Contraindications:     * Long-term use.     * Viral, bacterial, or fungal infections.     * Hypothyroidism or cirrhosis.     * Hypertension or heart failure.     * Psychosis or emotional instability.     * Diabetes.     * Glaucoma and cataracts.     * History of gastric or esophageal irritation.     * Children, pregnancy, and lactation.     * History of thromboembolic disorders or seizures.

  • Drug Interactions:     * Barbiturates, phenytoin (Dilantin), and rifampin.     * Estrogen and oral contraceptives.     * Nonsteroidal anti-inflammatory agents (NSAIDs) or salicylates.     * Diuretics.     * Live-virus vaccines and toxoids.     * Bupropion.     * Haloperidol.

Thyroid Disorders

  • Thyroid Gland Function: An endocrine gland responsible for regulating the rate of metabolism.

  • Hormonal Regulation:     * When thyroid levels are low, the pituitary gland releases TSH (Thyroid-stimulating hormone).     * TSH promotes the biosynthesis and secretion of two bioactive hormones:         * Thyroxine (T4).         * Triiodothyronine (T3): Recognized as the active form of thyroid hormone.

  • Hypothyroidism:     * Defined as diminished or absent thyroid function.     * Conditions requiring replacement therapy include Cretinism (congenital) and Myxedema (adult hypothyroidism).

  • Thyroid Agents (Replacement Therapy):     * Toxic Effects (Signs of Hyperthyroidism):         * Palpitations, chest pain, tachycardia, cardiac arrhythmias, and increased blood pressure.         * Nervousness, difficulty concentrating, tremor, muscle weakness, headache, and insomnia.         * Weight loss, diarrhea, and abdominal cramps.         * Intolerance to heat, fever, excessive sweating, and easy fatigability.         * Menstrual irregularities and exophthalmos.     * Cautions and Contraindications:         * Cardiovascular disease (angina pectoris, myocardial infarction, hypertension).         * Older adults.         * Adrenal insufficiency.         * Diabetes.     * Interactions:         * Food (must be taken on an empty stomach).         * Potentiation of oral anticoagulants (if added after warfarin therapy is stabilized).         * Insulin and oral hypoglycemics.         * Potentiation of adrenergic effects.         * Estrogens and oral contraceptives.         * Amiodarone; Aluminum/calcium/iron/magnesium salts; chromium; sucralfate.         * Soy products.

  • Hyperthyroidism:     * Causes include Graves’ disease and thyroiditis.     * Most Common Treatment: Orally administered radioactive iodine ablation (destruction) therapy.     * Outcome: Destruction or removal of the gland usually results in patients requiring lifelong hypothyroid treatment.

  • Antithyroid Agents:     * Used to relieve symptoms in preparation for surgery or radioactive iodine therapy, or for those who cannot undergo those procedures.     * Treatment of Choice: Methimazole.     * Side Effects:         * Rash, urticaria, and pruritus.         * Abnormal sense of taste.         * Blood dyscrasias, specifically agranulocytosis.     * Cautions and Contraindications:         * Prolonged therapy.         * Patients older than 4040 years.         * Pregnancy and lactation.         * Hepatic disorders (Black Box Warning associated with PTU/Propylthiouracil).     * Interactions:         * Other drugs causing agranulocytosis.         * Excessive iodine intake or drugs containing iodine.

Antidiabetic Agents and Diabetes Mellitus

  • Diabetes Mellitus (DM): A group of hormonal diseases resulting in elevated levels of blood glucose.

  • Classifications of DM:     * Type 1: Results from the destruction of pancreatic beta cells. Usually occurs in younger patients (less than 3535 years), has a rapid onset (ketoacidosis), and typically involves non-obese body composition. Management requires insulin injections.     * Type 2: Results from insulin resistance combined with relative insulin deficiency. Usually occurs in older, obese patients with a gradual onset. Management focuses on oral/injectable noninsulin medications, with insulin used only if needed.

Insulin Therapy

  • General Use:     * Required for Type 1 DM.     * Rarely used as first-line therapy for Type 2 DM.     * Commonly administered parenterally.

  • Product Types:     * Biosynthetic human insulins.     * Analog insulins.     * Standard concentration is U−100U-100.

  • Delivery Methods:     * Prefilled insulin pens (help avoid medication errors).     * Implantable programmable insulin pumps (continuous administration via catheter).     * Inhaled insulin (Brand name: Afrezza).

  • Actions and Administration:     * Ultra-rapid acting: Very short duration.     * Regular insulin: Rapid acting with a short duration.     * Corrective Dose Insulin: These rapid- or short-acting insulins are sometimes combined with isophane insulin.     * Mixing Rule: When drawing two insulins into the same syringe, the rapid- or short-acting insulin must be drawn first.

Blood Glucose Extremes: Hyperglycemia and Hypoglycemia

  • Hyperglycemia:     * Causes: Undiagnosed diabetes, insufficient insulin, infections, trauma, stress, endocrine disorders, pregnancy, or certain medications.     * Symptoms: Dehydration, excessive thirst, polyuria, fruity breath, lethargy, flu symptoms, vision problems, and ketoacidosis.     * Acute Treatment: IV fluids to correct electrolytes and addition of regular insulin to IV fluids.     * Interactions (Potentiation of hyperglycemia): Corticosteroids, epinephrine, atypical antipsychotics, protease inhibitors, thiazide diuretics, oral contraceptives, estrogen, and beta-blockers.     * Interactions (Potentiation of hypoglycemic effect of insulin): Alcohol, Monoamine oxidase inhibitors (MAOIs), salicylates, and anabolic steroids.

  • Hypoglycemia:     * Causes: Insulin overdose, delayed/insufficient food, excessive exercise, or changing insulin types (e.g., analog to human).     * Symptoms: Perspiration, pallor, hunger, irritability, confusion, tremor, blurred/double vision, tachycardia, shallow breathing, and loss of consciousness. In older adults, symptoms may mimic a Cerebrovascular Accident (CVA).     * Treatment (Conscious): Administration of 4 oz4\,oz of orange juice, candy, honey, or syrup (sublingual for faster absorption), followed by a protein snack (e.g., peanut butter, cheese, or milk).     * Treatment (Comatose): Administer 10−30 mL10-30\,mL of 50%50\% dextrose solution IV, or 0.5−1 unit0.5-1\,unit (1 mg1\,mg) glucagon (SC, IM, or IV), followed by a carbohydrate snack upon awakening.

Noninsulin Antidiabetic Agents for Type 2 Diabetes

  • Biguanides:     * Mechanism: Decrease hepatic glucose production and enhance insulin uptake in muscle tissue.     * Agent: Metformin (Preferred first-line monotherapy).     * Side Effects: GI effects, lactic acidosis, Vitamin B12B_{12} deficiency.     * Contraindications: Liver/kidney impairment, heart failure, radiocontrast dye administration.

  • Sulfonylureas (Oral Hypoglycemic Drugs):     * Mechanism: Increase insulin production from the pancreas and improve peripheral insulin activity.     * Side Effects: GI distress, dermatological effects, hypoglycemia (notably in older adults), weight gain, and water retention.     * Interactions: Potentiated by Beta-blockers, MAOIs, alcohol (disulfiram-like reaction), and NSAIDs. Antagonized by thyroid hormones, diuretics, and corticosteroids.

  • Alpha-Glucosidase Inhibitors:     * Mechanism: Delay digestion of complex carbohydrates and subsequent glucose absorption.     * Side Effects: High rate of GI effects, elevated liver enzymes.

  • GLP-1 Agonists (Incretin Mimetics):     * Mechanism: Mimic the naturally occurring GLP-1 hormone.     * Examples: Exenatide (Byetta).     * Weight Loss Specific: Tirzepatide (Zepbound), Liraglutide (Saxenda), and Semaglutide (Wegovy).     * Cautions: Not recommended for severe renal disease or history of pancreatitis.

  • DPP-4 Inhibitors:     * Usage: Monotherapy or combination; often preferred in older adults. Given orally once daily.     * Cautions: Pancreatitis history; requires dosage adjustment for renal disease (except linagliptin).

  • Meglitinides:     * Mechanism: Stimulate pancreatic beta cells to produce insulin.     * Agents: Nateglinide (Starlix) and repaglinide (Prandin).     * Administration: Must be taken before meals to maximize absorption.

  • Thiazolidinediones:     * Mechanism: Decrease insulin resistance.     * Agents: Pioglitazone (Actos) and rosiglitazone (Avandia).     Safety: Include Black Box Warnings. Prescribers must be registered with the Avandia-Rosiglitazone Medicine Access Program.     * Side Effects: Weight gain, edema, atypical bone fractures, and anemia.

  • SGLT2 Inhibitors:     * Mechanism: Decrease reabsorption of glucose in the kidneys.     * Side Effects: Vaginal yeast infections, urinary tract infections, and increased urge to urinate.

Questions & Discussion

  • Activity 23-1: Where is the pituitary gland located?     * Answer: At the base of the brain.

  • Activity 23-2: Which of the following is NOT a condition that can be treated by adrenal corticosteroids? (Malignancies, Ulcerative colitis, Hypertension, Respiratory disorders)     * Answer: Hypertension.

  • Activity 23-3: Which of the following is the treatment of choice for hyperthyroidism with antithyroid agents?     * Answer: Methimazole.

  • Activity 23-4: Which of the following are signs or symptoms of hyperglycemia? (Dehydration, Fruity breath, Shallow breathing, Sudden moodiness)     * Answer: Dehydration and Fruity breath.

  • Activity 23-5: Which of the following work by increasing insulin production from the pancreas and by improving peripheral insulin activity?     * Answer: Sulfonylureas.

  • Activity 23-6: Which of the following is the primary mechanism of action of SGLT2 inhibitors?     * Answer: Decreasing glucose reabsorption in the kidneys.