1. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Chapter 59 Drugs Related to Hypothalamic and Pituitary Function

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hypothalamus and Pituitary  Related anatomically and functionally  Regulate all bodily processes  15 hormones and regulatory factors 2

3. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Overview of Hypothalamic and Pituitary Endocrinology  Hormones of the anterior pituitary  Growth hormone (GH)  Corticotropin  Thyrotropin  Follicle-stimulating hormone (FSH)  Luteinizing hormone (LH)  Prolactin  Hormones of the posterior pituitary  Oxytocin  Antidiuretic hormone 3

4. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Growth Hormone  Biologic effects  Promotes growth  Promotes protein synthesis  Carbohydrate metabolism  Physiology  Regulation of release  Biologic effects  Promotion of protein synthesis  Effect on carbohydrate metabolism 4

5. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Growth Hormone  Pathophysiology  Deficiency Pediatric: Short stature, slowed growth, mental function not impaired, replacement therapy Adult: Reduced muscle mass  Excess Pediatric: Gigantism (7 to 9 feet tall)  Treatment: Removal of pituitary gland Adult: Acromegaly if epiphyses already closed  Treatment: Surgery, radiation, or drugs (octreotide [Sandostatin, Sandostatin LAR Depot], lanreotide [Somatuline Depot], and pegvisomant [Somavert]) 5

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Growth Hormone  Therapeutic uses  Pediatric growth hormone deficiency  Pediatric non–growth-hormone-deficient short stature  Pediatric short stature associated with Prader-Willi syndrome (PWS)  Adult growth hormone deficiency 6

7. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Growth Hormone  Adverse effects and interactions  Hyperglycemia  Neutralizing antibodies  Carpal tunnel syndrome  Fatality in patients with Prader-Willi syndrome  Interaction with glucocorticoids 7

8. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Insulin-Like Growth Factor-1  Mecasermin [Increlex]  Synthetic of natural insulin-like growth factor-1 (IGF-1)  Used in GH deficiency that is not responsive to GH treatment  Adverse effects Hypoglycemia, hypertrophy of tonsils, intracranial hypertension, vomiting, arthralgia, otitis media, elevation of serum aminotransferases and lipids, overgrowth of fat, facial bones, and kidneys 8

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Prolactin  Produced by anterior pituitary  Stimulates milk production after parturition  Effects of hypersecretion (excessive secretion)  Females: Amenorrhea, galactorrhea, infertility, possible delay of puberty in girls  Males: Reduced libido and potency, galactorrhea, possible delay of puberty in boys 9

10. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Prolactin  Treatment for hypersecretion  Suppression of prolactin release Cabergoline [Dostinex] Bromocriptine [Parlodel] 10

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Other Anterior Pituitary Hormones  Thyrotropin  Thyroid-stimulating hormone (TSH)  Corticotropin  Adrenocorticotropic hormone (ACTH)  Gonadotropins  Follicle-stimulating hormone (FSH)  Luteinizing hormone (LH) 11

12. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Antidiuretic Hormone  ADH (also known as vasopressin)  Promotes renal conservation of water  Works on the collecting ducts of the kidney to increase their permeability to water  Produced in the hypothalamus 12

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Antidiuretic Hormone  Therapeutic uses  Diabetes insipidus  Cardiac arrest  Postoperative abdominal distention  Preparation for abdominal radiography  Desmopressin for nocturnal enuresis (bedwetting)  Hemophilia A  Von Willebrand’s disease 13

14. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. ADH Use with Diabetes Insipidus  Diabetes insipidus  Deficiency of ADH Polydipsia (excessive thirst) Excretion of large volumes of dilute urine  Treatment: ADH replacement Desmopressin (agent of choice) Vasopressin  Adverse effects Water intoxication Excessive vasoconstriction 14

15. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Antidiuretic Hormone Antagonist  Conivaptan [Vaprisol]  Used in short-term IV therapy for hyponatremia in hospitalized patients with euvolemia and/or hypervolemia  Monitor serum sodium closely because of risk of hypernatremia  Tolvaptan  Oral vasopressin antagonist  Used to reduce hyponatremia in euvolemic or hypervolemic patients 15

16. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Oxytocin  Produced by hypothalamus  Stored in posterior pituitary  Two physiologic roles  Promotion of uterine contractions during labor  Stimulation of milk ejection during breast-feeding 16

17. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Acromegaly  Growth hormone excess  Pituitary adenoma  Clinical manifestations  Treatment  Surgery  Radiation  Somatostatin 17

18. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Somatropin [Humatrope]  Somatostatin analogs (octreotide and lanreotide) are the most effective drugs for suppressing GH release  Identical to human GH  Intramuscular (IM) or subcutaneous (subQ) administration 18

19. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Drugs Related to Hypothalamic Function  Seven regulatory factors in the hypothalamus  Only three have clinical applications Gonadotropin-releasing hormone (GnRH) and its synthetic analogs: Used to treat prostate cancer and endometriosis and to induce ovulation Corticotropin-releasing hormone (CRH): Used to diagnose adrenal disorders Somatostatin: Used to treat acromegaly  GnRH agonists  Leuprolide  Goserelin  Nafarelin  Gonadorelin 19