NUR 2390 endocrine

Study Notes for Pharmacology - Endocrine System

Overview of Endocrine System

  • **Key Hormones and Glands: **

    • Grouped under various glands, including:

    • Pituitary Gland (Master Gland)

    • Thyroid

    • Parathyroid

    • Adrenal Glands

    • Hormones include: Growth Hormone (GH), Thyroid Stimulating Hormone (TSH), Adrenocorticotropic Hormone (ACTH), Prolactin, Oxytocin, Anti-Diuretic Hormone (ADH)

Pituitary Gland

  • Description:

    • Often referred to as the "Master Gland" because it controls other endocrine glands.

    • Location: Directed by the hypothalamus and divided into two lobes:

    • Anterior Lobe:

      • Secretes:

      • Growth Hormone (GH) – Stimulates growth in tissues and bones

      • Thyroid Stimulating Hormone (TSH) – Acts on the thyroid gland

      • Adrenocorticotropic Hormone (ACTH) – Stimulates adrenal gland

      • Gonadotropins (Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) – Affect testosterone and estrogen production in testes and ovaries

    • Posterior Lobe:

      • Secretes:

      • ADH – Acts on kidneys and blood vessels

Hormonal Regulation

  • Negative Feedback Loop:

    • Endocrine glands operate using a negative feedback loop:

    • If conditions in the body change from a set point, corrective mechanisms are activated until conditions return to that set point.

Growth Hormone (GH)

  • Production and Regulation:

    • Hypothalamus:

    • Secretes Growth Hormone-Releasing Hormone (GHRH) – Stimulates PITUITARY to release GH

    • Secretes Growth Hormone-Inhibitory Hormone (GHIH) – Inhibits GH release from PITUITARY

  • Action of GH:

    • Promotes growth of bones, muscle, and body tissues/organs (no specific target gland)

  • Deficiencies:

    • In Childhood:

    • Leads to short stature syndrome; GH replacement can improve short stature syndrome if administered before epiphyses close.

    • Prevents pituitary dwarfism (different from primordial dwarfism)

    • In Adulthood:

    • Short stature syndrome / pituitary dwarfism may become permanent; characterized by doll facies, obesity, high-pitched voice, muscle atrophy.

    • Patients with chronic illness (e.g., HIV) or muscle-wasting diseases may benefit from GH administration.

    • Illicit use seen in bodybuilding and strength training.

Growth Hormone Replacement Therapy

  • Somatropin:

    • Identical amino acid sequence to Human Growth Hormone (HGH)

    • Administration: Not orally (destroyed by GI enzymes), subcutaneous (SQ) or intramuscular (IM) (not IV)

    • Costly treatment

    • Long-term effects on insulin secretion leading to diabetes mellitus (DM).

    • Not to be used with corticosteroids.

    • Not effective for growth deficiency caused by Prader-Willi syndrome.

  • Side Effects of Somatropin:

    • Includes:

    • Paresthesias, arthralgia, myalgia, edema, headache

    • Glucose fluctuations, hypothyroidism, hematuria

    • Flu-like symptoms

  • Adverse Reactions:

    • Seizures, increased intracranial pressure, leukemia

  • Somatrem:

    • Similar to somatropin but with an extra amino acid.

Growth Hormone Excess

  • Causes:

    • Most commonly a pituitary tumor.

  • Consequences:

    • May lead to Gigantism or Acromegaly.

  • Treatment Options:

    • Removal or radiation of the tumor

    • Bromocriptine (Dopamine agonist) - reduces GH production

    • Pegvisomant (blocks GH action)

    • Octreotide (somatostatin agonist - suppresses GH release)

  • Note: Treatments are costly, and GI side effects are common.

Thyroid Gland

  • Function:

    • Regulates metabolic rate.

  • Hormonal Regulation:

    • Hypothalamus secretes Thyrotropin-Releasing Hormone (TRH) → stimulates PITUITARY to release TSH → stimulates thyroid to secrete T3 (triiodothyronine) and T4 (thyroxine).

  • Hypothyroidism:

    • Underactive thyroid results in low T3 and T4 levels.

    • Consequences: Increased TRH and TSH as negative feedback.

  • Hyperthyroidism:

    • Overactive thyroid leads to high T3 and T4 levels.

    • Consequences: Decreased TRH and TSH as negative feedback.

Iodine and Thyroid Function

  • Importance:

    • Iodine is essential for the production of T3 and T4

    • Consequences of Deficiency:

    • Leads to thyroid dysfunction and goiter.

Goiter

  • Primary Cause:

    • Iodine deficiency is the most common cause, leading to enlarged thyroid trying to capture more iodine for hormone production.

  • Other Causes:

    • Graves' Disease

    • Hashimoto's Thyroiditis

    • Nodules or thyroid cancer

Thyroid Dysfunction Causes

  • Primary: Issues with the thyroid itself (more frequent).

    • Indications: Thyroid dysfunction reflects inverse relationship with TSH:

    • Hypothyroid = LOW T3/T4 & HIGH TSH

    • Hyperthyroid = HIGH T3/T4 & LOW TSH.

  • Secondary: Tumor or issue with pituitary affecting TSH release.

Causes and Treatment of Hypothyroidism

  • Primary Causes:

    • Thyroid gland disorder - frequent; indicated by low T3/T4 and elevated TSH (could be due to Hashimoto’s, excessive therapy, surgery).

    • Treatment:

    • Synthetic T3/T4 replacement (Levothyroxine (T4) most common).

    • Liothyronine (T3) for rapid severity treatment.

  • Secondary Causes:

    • Pituitary issues - indicated by low TSH and low T3/T4 levels.

    • Treatment: Address pituitary issue (e.g., surgery).

Symptoms of Hypothyroidism

  • Common symptoms:

    • Lethargy, apathy, memory impairment, emotional changes, slow speech, cold intolerance, thick dry skin, weight gain.

  • Severe cases: MYXEDEMA coma.

  • In children: Leads to Cretinism (stunted growth).

Drug Therapy for Hypothyroidism

  • Uses: Treatment for hypothyroidism, myxedema, and cretinism.

  • Levothyroxine Sodium:

    • Pregnancy Category: A

    • Drug interactions: Increased effects of anticoagulants and decreased effects of antidiabetics.

    • Side effects include headache, nausea, vomiting, diarrhea, cramps.

    • Contraindicated in thyrotoxicosis, myocardial infarction, severe renal disease.

    • Caution advised in patients with cardiovascular disease.

    • Adverse reactions: Tachycardia, hypertension, palpitations, life-threatening thyroid crisis, angina, dysrhythmias.

Pharmacokinetics of Levothyroxine Sodium

  • Mechanism: Increases metabolic rate and oxygen consumption.

  • Pharmacodynamics:

    • Absorption: PO 50-75% (must be taken on an empty stomach).

    • IV onset: 6-8 hours; PO peak: 24-48 hours; duration: up to 1-3 weeks.

    • Distribution: 99% protein-bound, excreted in bile and feces.

Hyperthyroidism

  • Primary Causes:

    • Usually Graves' Disease (hyperfunction of the thyroid).

    • Symptoms: Rapid pulse, weight loss, excessive perspiration, heat intolerance, nervousness, irritability, exophthalmos.

  • Severe Cases: Thyroid Storm (life-threatening).

  • Treatment Options: Surgery, radioactive iodine, medications to inhibit secretion.

  • Secondary Causes: Pituitary issues secreting too much TSH.

Drug Therapy for Hyperthyroidism

  • Thiourea Derivatives:

    • Reduce thyroid hormone production (e.g., PTU, Methimazole).

    • Side effects mimic hypothyroid symptoms.

    • Prolonged use can cause goiter due to increased TSH secretion.

Antidiuretic Hormone (ADH)

  • Production: Produced in the posterior pituitary.

    • Function: Promotes water reabsorption from renal tubules, maintaining fluid balance in the body.

ADH Abnormalities

  • Deficiency: Leads to Diabetes Insipidus - increases urine production (diuresis), fluid loss, dehydration, hypotension, electrolyte disturbances.

  • Excess: Leads to Syndrome of Inappropriate Antidiuretic Hormone (SIADH) - causes water retention, fluid overload, CHF exacerbation, hyponatremia.

Treatment for Diabetes Insipidus

  • Replacement Therapy:

    • Vasopressin (Pitressin) - IM, SQ, or intranasal; serious side effect is hyponatremia; contraindicated in severe renal disease.

    • Desmopressin acetate (DDAVP) - used similarly, also indicated for nocturnal enuresis.

Parathyroid Glands

  • Function: Secrete Parathyroid Hormone (PTH), regulating calcium levels.

  • Mechanism of Action:

    • PTH secretion increases when serum calcium decreases.

    • Enhances osteoblast activity, calcium resorption from renal tubules and intestines (via Vitamin D).

Parathyroid Abnormalities

  • Deficiency (Hypoparathyroidism):

    • Caused by damage to glands or low magnesium; leads to hypocalcemia.

  • Excess (Hyperparathyroidism):

    • Usually due to malignancy; causes hypercalcemia.

Treatment for Hypoparathyroidism

  • Calcium Supplementation:

    • Calcitriol (Vitamin D analogue) enhances calcium absorption; Ergocalciferol enhances sodium and phosphorus absorption.

    • NATPARA - recombinant human PTH therapy available SQ.

Calcitriol Action and Pharmacokinetics

  • Use: Treats hypoparathyroidism and manages hypocalcemia in chronic renal failure.

  • Pharmacokinetics:

    • Absorption (PO) forms are effective, onset 2-6 hours, peak 10-12 hours, half-life around 3-8 hours, mainly excreted in feces.

Calcitonin

  • Thyroid Hormone: Besides T3 and T4, also produced by the thyroid to regulate calcium levels.

    • Released in response to increased serum calcium levels, stimulates osteoclast activity and calcium deposition.

Treatment for Hyperparathyroidism

  • Surgery: Partial/total parathyroidectomy is preferred.

  • Medications for hypercalcemia:

    • Salmon-derived calcitonin, intranasally (only if no fish allergy); adverse effects include hypocalcemia, tetany.

    • Cinacalcet - reduces PTH secretion, helps slow bone destruction.

    • Bisphosphonates assist with osteoporosis management.

Adrenal Glands Overview

  • Structure: Comprised of adrenal cortex and adrenal medulla.

  • Function: Produce glucocorticoids (e.g., cortisol) and mineralocorticoids (e.g., aldosterone).

Glucocorticoids (Cortisol)

  • Function: Affected by ACTH release; influences carbohydrate, protein metabolism, muscle activity.

  • Common Effects: Antiinflammatory, antiallergic, antistress impact, but long-term use increases side effects (e.g., fluid retention).

  • Common Drugs: Prednisone, methylprednisolone, dexamethasone.

Prednisone Overview

  • Uses: Decrease inflammation; immunosuppressant for various conditions.

  • Cautions:

    • Numerous drug interactions (e.g., with digoxin).

    • Side effects include hypertension, mood changes, weight gain, and serious complications like GI hemorrhage.

Corticosteroid Effects

  • Short-term vs Long-term Effects:

    • Long-term use leads to adrenal atrophy, necessitating careful tapering of doses.

Addison’s Disease

  • Description: Adrenal insufficiency leading to severe symptoms, requiring steroid therapy for life.

Cushing Syndrome

  • Description: Caused by overproduction of cortisol, usually due to pituitary or adrenal tumors; symptoms often parallel those of steroid therapy side effects.