Pituitary gland drugs

• Hypothalamus & Pituitary Hormones


  Hormones secreted by the hypothalamus and the pituitary that are peptides or glycoproteins that act by binding to specific receptors

  
• Hormones of the anterior pituitary


  • Regulated by neuropeptides called "releasing" or "inhibiting" factors or hormones produced in the hypothalamus
  • Reach the pituitary by the hypophyseal portal system

  
• Each hypothalamic regulatory hormone controls the release of a specific hormone from the anterior pituitary

  
• Pituitary hormone preparations are currently used for specific hormonal deficiencies, although most of the agents have limited therapeutic applications

  
• Hormones of the anterior pituitary are administered intramuscularly (IM), subcutaneously, or intranasally because their peptidyl nature makes them susceptible to destruction by proteolytic enzymes of the digestive tract

  
• Adrenocorticotropic hormone (ACTH)


  Corticotropin-releasing hormone (CRH) is responsible for the synthesis and release of ACTH by the pituitary

  
• ACTH is released from the pituitary in pulses with an overriding diurnal rhythm, with the highest concentration occurring in early morning and the lowest in late evening
• Stress stimulates ACTH secretion, whereas cortisol acting via negative feedback suppresses its release
• ACTH action


  1. Binds to receptors on the surface of the adrenal cortex

  2. Stimulates the conversion of cholesterol to pregnenolone

  3. Stimulates the synthesis and release of adrenocorticosteroids and the adrenal androgens

  
• Therapeutic uses of ACTH


  • Mainly used as a diagnostic tool for differentiating between primary adrenal insufficiency (Addison disease) and secondary adrenal insufficiency (caused by inadequate secretion of ACTH by the pituitary)
  • Also used in the treatment of infantile spasms and multiple sclerosis
• Short-term use of ACTH for diagnostic purposes is usually well tolerated, but with longer use, toxicities are similar to glucocorticoids and include hypertension, peripheral edema, hypokalemia, emotional disturbances, and increased risk of infection
• Growth hormone (somatotropin)


  • Released by the anterior pituitary in response to growth hormone (GH)-releasing hormone
  • Secretion of GH is inhibited by the hormone somatostatin
  • GH is released in a pulsatile manner, with the highest levels occurring during sleep
  • With increasing age, GH secretion decreases, accompanied by a decrease in lean muscle mass

  
• Synthetic human GH (somatropin) is produced using recombinant DNA technology
• Mechanism of action of GH


  Many physiologic effects of GH are exerted directly at its targets, others are mediated through the somatomedins—insulin-like growth factors 1 and 2 (IGF-1 and IGF-2)
• GH administered to adults increases lean body mass, bone density, and skin thickness, and decreases adipose tissue, leading to off-label use by older individuals and athletes seeking to enhance performance
• Somatropin is administered by subcutaneous or IM injection, and although the half-life of GH is short, it induces release of IGF-1 from the liver, which is responsible for subsequent GH-like actions
• Somatropin should not be used in pediatric patients with closed epiphyses, patients with diabetic retinopathy, or obese patients with Prader-Willi syndrome
• Somatostatin (growth hormone–inhibiting hormone)


  • In the pituitary, somatostatin binds to receptors that suppress GH and thyroid-stimulating hormone (TSH) release
  • Originally isolated from the hypothalamus, somatostatin is a small polypeptide found in neurons throughout the body as well as in the intestine, stomach, and pancreas
  • Somatostatin not only inhibits release of GH but also insulin, glucagon, and gastrin

  
• Somatostatin analogs


  • Octreotide and lanreotide
• Gonadotropin-releasing hormone (GnRH)


  • Pulsatile secretion of GnRH from the hypothalamus is essential for release of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary
  • Continuous administration of GnRH analogs, such as leuprolide, is effective in suppressing production of FSH and LH

  
• Gonadotropins (FSH and LH)


  • Produced in the anterior pituitary
  • Regulation of gonadal steroid hormones depends on these agents
  • Used in the treatment of infertility

  
• Menotropins (hMG)


  • Obtained from urine of postmenopausal women and contain both FSH and LH
• Urofollitropin


  • FSH obtained from postmenopausal women
• Menstrual cycle


  Occurs in females starting around 8 years of age
• Menopause


  Occurs when menstrual cycles stop
• Symptoms of menopause include depression and sweating
• Sex hormones


  Regulated by GnRH
• GnRH analogue treatment


  1. Suppresses sex hormones

  2. Used in breast and prostate cancer
• GnRH antagonist treatment


  1. Inhibits LH secretion

  2. Prevents premature ovulation

  3. Allows multiple follicles to mature

  
• Gonadotropins


  • FSH
  • LH
• Menotropins


  Human menopausal gonadotropins containing both FSH and LH, obtained from urine of postmenopausal women
• Urofollitropin


  FSH obtained from postmenopausal women, devoid of LH
• Follitropin alfa and follitropin beta

  Recombinant human FSH products
• Human chorionic gonadotropin (hCG)


  Placental hormone excreted in urine of pregnant women, effects similar to LH

  
• All gonadotropin hormones are injected via IM or subcutaneous route
• Gonadotropin treatment for infertility


  1. Injection of hMG or FSH over 5-12 days causes ovarian follicular growth and maturation

  2. Subsequent injection of hCG triggers ovulation

  
• Adverse effects of gonadotropin treatment


  • Ovarian enlargement
  • Possible ovarian hyperstimulation syndrome, which may be life threatening
  • Multiple births can occur
• Oral contraceptives cannot be used in infertility treatment as the ovaries are small
• Gonadotropin treatment is used to induce ovulation in infertility
• Increased prolactin levels


  Cause infertility and decreased sexual drive