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Pharm Exam 3 > Hypothalamic and Pituitary Hormones > Flashcards

Hypothalamic and Pituitary Hormones Flashcards

1
Q

_____________: integrates information received from various parts of the brain, humoral factors and physiochemical parameters from the circulation

A

Hypothalamus

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2
Q

What part of the pituitary is composed of axons of hypothalamic neurons and, thus, is an extension of the hypothalamus?

A

Posterior pituitary

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3
Q

What part of the pituitary is known as the master gland and why?

A

Anterior pituitary because it regulates the activities of all major organs of the body.

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4
Q

What part of the pituitary receives hypothalamic hormonal inputs through the hypothalamic hypophyseal portal vein system, which collects venous blood from the hypothalamus and drains it to the pituitary?

A

Anterior pituitary

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5
Q

What are the pharmacological applications for pituitary hormones?

A

1) Replacement therapy for hormone deficiency
2) Antagonists for diseases of hormone production
3) Diagnostic tool for identifying endocrine disorders

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6
Q

What type of capillaries are seen in the pituitary portal vein circulation?

A

Fenestrated capillaries which results in easy access of releasing hormones from the hypothalamus to the anterior pituitary

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7
Q

What are the different hormones released from the hypothalamus?

A
  • Growth Hormone Releasing Hormone (GHRH)
  • Gonadotropin-Releasing Hormone (GnRH)
  • Thyrotropin-Releasing Hormone (TRH)
  • Corticotropin-Releasing Hormone (CRH)
  • Dopamine (DA)
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8
Q

What is another name for Corticotropin-Releasing hormone?

A

Corticorelin

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9
Q

What are the different hormones released from the Anterior pituitary?

A
  • Growth Hormone (GH)
  • Luteinizing Hormone (LH)
  • Follicle Stimulating Hormone (FSH)
  • Prolactin
  • Thyroid-Stimulating Hormone
  • Adrenocorticotropin (ACTH)
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10
Q

What are the different hormones released from the posterior pituitary?

A
  • Oxytocin

- Vasopressin (Antidiuretic hormone, ADH)

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11
Q

Which pituitary hormone is used to distinguish Cushing’s syndrome from ectopic ACTH secretion?

A

Corticorelin/CRH

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12
Q

An increase in TRH leads to an increase in TSH which leads to an increase in what?

A

Thyroxine (in thyroid)

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13
Q

An increase in CRH leads to an increase in ACTH which leads to an increase in what?

A

Glucocorticoids and mineralocorticoids (adrenal cortex)

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14
Q

An increase in GnRH leads to an increase in FSH and LH. When these hormones increase what occurs and where?

A

Increase in sex steroids in gonads due to LH

Increase in inhibit in gonads due to FSH

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15
Q

An increase in GNRH leads to an increase in GH, which leads to an increase in what?

A

Insulin-like growth factor-1 (IGF-1) which is in the liver, muscles, bone, and kidney

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16
Q

What are the pituitary inhibiting hormones and what do they do?

A
  • Somatostatin: Decrease in GH and TSH

- Dopamine: Decrease in prolactin and in high doses, decrease in GH as well.

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17
Q

What hormones are secreted by the hypothalamus and act directly on the periphery? What do they do?

A
  • Arginine Vasopressin: regulation of renal water conservation
  • Oxytocin: Milk-let down and partuition (child birthing)
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18
Q

Growth promotion in humans is mediated by regulating the production of which factors?

A

IGF-1 and IGF-2 (insulin-growth factor)

These factors are insulin-like and can cause hypoglycemia

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19
Q

What hormone is involved in lipid and carbohydrate metabolism, and promotes lean body mass and bone density?

A

Growth Hormone

Anabolic effects in muscle and catabolic effects in lipid cels

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20
Q

What does a deficiency of GH in childhood result in?

A

Failure to reach adult height and increased body fat and decreased muscle mass.

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21
Q

What does a deficiency of GH in adulthood result in?

A

Decreased lead body mass, obesity, asthenia (weakness), and reduced cardiac output

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22
Q

What are the pharmacokinetics of GH?

A

Plasma half-life: 20-25 minutes, undergoes hepatic clearance

Administration: Subcutaneous injections 6-7 times per week; peak plasma concentration is 2-4 hours

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23
Q

GH promotes ____________ growth indirectly until the closure of the epiphyses at the end of puberty.

A

LONGITUDINAL

GH promotes LONGITUDINAL growth indirectly until the closure of the epiphyses at the end of puberty.

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24
Q

GH effects are mediated through which cytokine receptor superfamily?

A

JAK/STAT

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25
Q

GH (increases/decreases) insulin sensitivity.

A

Decreases

GH DECREASES insulin sensitivity -> Mild hyperinsulinemia

-Increases blood glucose and free fatty acids

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26
Q

What is the recombinant form of growth hormone used to treat growth hormone deficiency (can be genetic or the result of trauma to the pituitary or hypothalamus)?

A

Somatropin (rGH)

27
Q

Patients with short bowel syndrome who are dependent on total parenteral nutrition (TPN) should be given what? why?

A

GH in combination with glutamine

This has trophic effects on the intestinal mucosa, increasing growth and function.

28
Q

T/F - GH is used for anti-aging remedy.

A

False - There are unsubstantial claims as an “anti-aging” remedy - it has actually been shown to decrease life-span in animal models.

29
Q

What are some reasons that GH is used to treat non-GH deficiencies?

A
  • Prader-Willi syndrome
  • Turner’s syndrome
  • Renal insufficiency pre-transplant
  • Idiopathic short stature (ISS)
30
Q

What is Prader-Willi syndrome and how will treating a patient with GH help?

A

It is an autosomal dominant genetic disease that is associated with growth failure, obesity, and carbohydrate intolerance

Treatment increase lean body mass, linear growth, and energy expenditure.

31
Q

What is Turner’s syndrome (45 X) and how will treating a patient with GH help?

A

This is a genetic disease where there is a congenitally missing X chromosome. Patients have a short stature, webbed neck and underdeveloped gonads.

High-dose treatment effective in increasing height 4-6 inches. It is combined treatment with sex steroids.

32
Q

What is definition of Idiopathic short stature?

A

> 2.25 standard deviations below the norm.

Many years of treatment result in an average increase of adult height from 1.57-2.67 inches

Cost is $5-40K annually - Cost risk benefit

33
Q

T/F - GH is well tolerated in children and side effects are rare.

A

True

34
Q

What are some of the adverse effects for children when taking GH?

A
  • Pseudotumor cerebri, slipped capital femoral epiphysis, progression of scoliosis, peripheral edema, muscle pain, hyperglycemia
  • Prader-Willi or patients with sleep apnea: increased risk of asphyxiation in severely obese patients
  • Treatment with GH requires periodic evaluation of anterior pituitary hormones to monitor deficiency in hydrocortisone, levothyroxine, or gonadal hormones and diabetes
  • Contraindications: Diabetic retinopathy, epiphyseal closure, trauma, obesity, neoplastic disease (tumors).
35
Q

What is used for treatment in children with growth failure that have severe IGF-1 deficiency and that are unresponsive to GH?

A
  • Mecasmerin (Increlex)

- Mecasermin rinfibrate (IPLEX)

36
Q

Wy are Mecasmerin and Mecasermin used instead of just GH?

A

GH has a short half life (20-25 mins). These drugs are combinations of rhIGF-1 and rhIGF-3, which significantly increases the circulating half life of rhIGF-1.

37
Q

What are the adverse effects of Mecasmerin and Mecasermin?

A

Hypoglycemia, intracranial hypertension and elevation of liver enzymes.

Patients are told to consume carbohydrate-containing meals 20 minutes prior to drug administration

38
Q

What is Somatostatin and where is it released?

A

Somatostatin is a 14-amino acid peptide that is the most widely distributed hypothalamic hormone. It is also produced in pancreatic D cells

39
Q

What is the action of somatostatin?

A

It inhibits the release of growth hormone, insulin, glucagon, and gastrin.

40
Q

What is somatostatin’s half life and is it used greatly in the treatment of patients with GH excess?

A

Half life: 1-3 minutes (Very short)

Somatostatin has limited clinical usefulness due to its short duration.

It is metabolized and excreted via renal system (kidneys).

41
Q

Somatostatin inhibits which two factors?

A

Inhibits GH and TH

This causes there to be a decrease in GH and TH.

42
Q

What is Octeotide (Sandostatin)?

A

Somatostatin analog with a much longer half life of 80 minutes.

40 Xs more potent than somatostatin in inhibiting GH

2 Xs more potent than somatostatin in inhibiting Insulin

Can be given as long acting medicine (IM injections)

43
Q

What are the clinical indications for Octeotide (Sandostatin)?

A

Acromegaly, Thyrotropin pituitary adenoma and carcinomas, Gastrinoma, acute bleeding control from esophageal varicose, glucagonoma

44
Q

What are the adverse effects of Octeotide (Sandostatin)?

A
  • Significant gastrointestinal disturbances
  • Biliary sludge/gallstones (frequency 20-30% (>6 mos treatment))
  • Sinus bradycardia (25% frequency)
  • Conduction disturbances (10%)
45
Q

What four drugs are used to treat acromegaly?

A

1) Octreotide (Sandostatin)
2) Lanreotide (Somatuline)
3) Pegvisomant (Somavert)
4) Bromocriptine (Parlodel)

All have soma- except my Bro

46
Q

What is Lanreotide (Somatuline)?

A
  • Long acting drug used to treat acromegaly

- Equally as efficacious to octreotide in reducing GH levels and normalizing IGF-1 concentrations

47
Q

What is Pegvisomant (Somavert)? Use, MOA, Adverse Effects

A
  • GH receptor antagonist
  • Allows for GH receptor dimerization, but blocks the conformational changes needed for signal transduction.
  • Used for acromegaly - reduction and subsequent normalization of IGF-1
  • Adverse effects: Pain at injection sight, swelling of limbs, chest pain, hypoglycemia, and nausea
48
Q

What is Bromocriptine (Parlodel)?

A
  • Dopamine D2 receptor agonist (More effective at inhibiting prolactin secretion)
  • In high doses will inhibit GH
  • Used in treatment of small GH-secreting tumors (Acromegaly)
49
Q

Where is gonadotropin-releasing hormone produced?

A

Arcuate nucleus of the hypothalamus

50
Q

Pulsatile secretion of GnRH is necessary for the production of which two hormones?

A

FSH & LH

51
Q

_______________ is the acetate salt of synthetic human GnRH.

A

Gonadorelin

52
Q

What are some synthetic forms of GnRH that are more potent and longer lasting?

A
  • Leuprolide (Lupron)
  • Nafarelin (Synarel)
  • Goserelin (Zoladex)
  • Histerlin (Supprelin)
  • Triptorelin (Trelstar)

*Leuprolide and the -relins

53
Q

When theres a pulsatile IV of GnRH analogs, how frequent is it given?

A

Every 1-4 hours

54
Q

Can GnRH synthetic drugs be used over a long period of time?

A

No, long term use is avoided because of toxicity.

55
Q

How is delayed puberty tested to see if its due to constitutional delay or hypogonadotropic hypogonadism?

A

LH response is tested following subcutaneous GnRH bolus.

  • Peak LH > 15.6 mlU/mL = Normal (indicating puberty will occur soon)
  • Peak LH response impaired suggests hypogonadotropic hypogonadism (probably indicative of pituitary/hypothalamic dysfunction but it does not rule out constitutional delay).
56
Q

T/F - GnRH analogs can be used for both stimulation as well as inhibition of different things.

A

TRUE

57
Q

How are GnRH analogs used in stimulation?

A
  • Infertility due to hypothalamic hypogonadotropic hypogonadism (both sexes), used to stimulate pituitary function
  • Programmable pump technology allows pulsatile GnRH treatment (frequency: every 90 minutes) - patient has to take into account inconvenience/cost issues
58
Q

What are some different things that GnRH analogs are used for inhibition?

A
  • Prostate cancer
  • Endometriosis
  • Uterine Leiomyomata (fibroids)
  • Precocious puberty
59
Q

GnRH analog agonists along with androgen receptor antagonists are used to help in the treatment of _________________________.

A

Prostate cancer

These drugs reduce circulating testosterone levels. During the “flare period” patients can experience pain in patients with bone metastases, tumor growth, and can worsen urinary obstruction.

60
Q

Why are GnRH analog agonists used in endometriosis?

A

Diminishes pain by elimination of cyclic changes to estrogen and progesterone.

Treatment is max 6 months due to a decrease in bone density as a result of ovarian suppression.

61
Q

Why is treatment of endometriosis with GnRH analog agonists limited to 6 months only?

A

Decrease in bone density due to ovarian suppression

62
Q

What drugs are used to reduce fibroid size in uterine leiomyomata (fibroids)?

A

Leuprolide
Goserlin
Nafarelin

63
Q

How long are the drugs used to reduce fibroid size in uterine leiomyomata (fibroids)?

A

Used for 3-6 months plus supplemental iron to reduce anemia

64
Q

What type of drugs are used to treat precocious puberty and when do children start taking it?

A

GnRH analog agonists used to slow puberty. Given to children who start to show secondary sex characteristics early (females- 7&8 and males 9).

1 month IM injection of Leuprolide, or yearly implant of Histrelin acetate

Treatment until 11 in females and 12 in males.

Pharm Exam 3 (4 decks)

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