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Pharm > Hypothalamic and Pituitary Hormones > Flashcards

Hypothalamic and Pituitary Hormones Flashcards

1
Q

What is a negative regulator of GH?

A

Somatostatin

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2
Q

What is a negative regulator of prolactin?

A

Dopamine

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3
Q

The effects of GH are mediated through

A

IGF-1

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4
Q

Physiological Actions of GH in childhood

A

Promotes linear growth

Growth of long bones, cartilage, muscle, organ systems

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5
Q

Physiological Actions of GH in adulthood

A

Increases protein synthesis and bone density
Promotes lipolysis, inhibits lipogenesis
Promotes gluconeogenesis and glucose release
Opposes insulin-induced glucose uptake in adipose tissue, reduces insulin sensitivity

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6
Q

Features of GH deficiency in children

A

short stature
Adiposity
hypoglycemia

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7
Q

Features of GH deficiency in adults

A 
increased generalized adiposity
Decreases skeletal muscle mass
decreased bone density
Cardiac muscle atrophy
Atherogenic blood lipid profile
Fatigue, weakness, depression, malaise
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8
Q

synthetic GHRH

A

Sermorelin

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9
Q

Sermorelin (synthetic GHRH) indication

A

used if defective GHRH release but normally functioning anterior pituitary somatotrophs

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10
Q

Recombinant human GH

A

Somatropin

Somatrem

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11
Q

Recombinant IGF-1

A

Mecasermin

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12
Q

Mecasermin (recombinant IGF-1) indication

A

Used in children where IGF-1 deficiency is due to mutations of GH receptor: Laron dwarfism or Ab against GH

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13
Q

Somatropin formulation

A

191-amino acid peptide, identical to native hGH

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14
Q

Somatrem

A

192-amino acid peptide consistign of 191aa of GH plus extra methionine residue at N-terminus (for stability, less allergic response)

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15
Q

Recombinant hGH (somatropin, somatrem) MOA

A

replaces GH

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16
Q

Recombinant hGH (somatropin, somatrem) Indications

A 
Documented growth failure in pediatric pts with:
GH deficiency
Chronic renal failure
Prader-Willi syndrome
Turner syndrome

SGA w/ failure to catch up by 2
Idiopathic short stature, non GH-deficient (>2.25 S.D. below mean height)

GH deficiency in adults
Wasting in AIDS pts
Short bowel syndrome

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17
Q

Recombinant hGH (somatropin, somatrem) efficacy in children

A

Increases linear growth
Weight gain
Increases muscle mass, organ size, RBCs

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18
Q

Recombinant hGH (somatropin, somatrem) efficacy in adults

A 
Increases bone mineral density
Decreased central adiposity
Increases muscle mass
Improves lipid profile
Improves cardiac function
Improves sense of well being
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19
Q

Recombinant hGH (somatropin, somatrem) side effects

A 
Leukemia
Rapid growth of melanocytic lesions
Hypothyroidism (GH counteracts TSH)
Insulin resistance
Arthralgia
Increase in cytochrome p450 activity
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20
Q

Recombinant hGH (somatropin, somatrem) contraindications

A 
Ped pts with closed epiphyses
Intracranial lesion
Active malignancy
Proliferative diabetic retinopathy
Cautin in diabetes
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21
Q

What is the effect of glucocorticoids on somatropin

A

Inhibit growth-promoting effect

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22
Q

What is the most common cause of growth hormone excess

A

Benign anterior pituitary tumor

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23
Q

Growth hormone excess in children

A

Gigantism

Occurs before the closure of epiphyses because excess IGF1 causes excessive longitudinal bone growth

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24
Q

Growth hormone excess in adults

A

Acromegaly

Occurs after epiphyses close, IGF-1 promotes growth of deep organs and cartilaginous tissue

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25
Q

Characteristics of acromegaly

A

thickening of bone (face, hands)
Large facial structure
Macroglossia
Hepatomegaly

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26
Q

Standard treatment for larger pituitary adenoma

A

Transsphenoidal surgery to remove the tumor

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27
Q

Medical options for smaller adenomas

A

Somatostatin analogues
GH receptor antagonist
Dopamine receptor agonist

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28
Q

Somatostatin analogues

A

Octreotide

Lanreotide (Europe)

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29
Q

GH receptor antagonist

A

Pegvisomant

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30
Q

Dopamine receptor agonist

A

Bromocriptine

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31
Q

Octreotide

A

Synthetic long-lasting peptide analogue of somatostatin

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32
Q

Octreotide MOA

A

Inhibits GH secretion

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33
Q

Octreotide indication

A

Control pituitary adenoma growth in acromegalic patients
Carcinoid crisis (flushing, diarrhea)
Secretory diarrhea from VIPoma
To control acute GI bleeding

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34
Q

Octreotide Side Effects

A

Nausea, vomiting, abdominal cramps, GI discomfort
Cardiac effects
Hypoglycemia
Gallstones

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35
Q

Octreotide Therapeutic Considerations

A

Decreases cyclosporin levels

Increases the availability of bromocriptine

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36
Q

GH Receptor Antagonist

A

Pegvisomant

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37
Q

Pegvisomant structure

A

Recombinat protein of 191 aa with mutliple polyethylene glycol (PEG) residues -prolongs half life

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38
Q

Pegvisomant MOA

A

Normally GH binds 2 receptors, dimerizes > signal transduction. Pegvisomant does not bind to the 2nd receptor, blocks signal transfuction = competitive antagonist of GH
Decreases serum IGF-1

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39
Q

Pegvisomant Indications

A

Acromegaly that is refractory to other treatment

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40
Q

Pegvisomant side effects

A

Increased pituitary adenoma size

Elevated serum aminotransferase levels

41
Q

Pegvisomant Therapeutic Considerations

A

Should have yearly MRI to exclude enlarging adenoma

Liver function tests periodically

42
Q

What do the gonadotroph cells in the pituitary secrete in response to pulsatile GnRH?

A

LH and FSH

43
Q

What is the function of FSH in women?

A

Ovarian follicle development

FSH stimulates conversion of androgens to estrogens in the granulosa cells

44
Q

What is the function of LH in women?

A

Stimulates androgen production in the ovary (theca cells)

45
Q

What is the function of FSH in men?

A

Regulates spermatogenesis

Produces androgen binding protein

46
Q

What is the function of LH in men?

A

Stimulates production of testosterone by the Leydig cells

47
Q

Gonadotropins

A

Human menopausal gonadotropins, menotropins
Human chorionic gonadotropin
Urofollitropin
Follitropin

48
Q

Gonadotropin Releasing Hormone analogue (short half-life)

A

Gonadorelin

stimulatory-pulsatile form

49
Q

Gonadotropin Releasing Hormone analogue (long half-life)

A

Goserelin, Histrelin, Leuprolide, Nafarelin, Triptorelin

inhibitory-continuous form

50
Q

GnRH receptor antagonists

A

Ganirelix, Cetrorelix, Abarelix

51
Q

Menotropins

A

Obtained from the urine of menopausal women

Contain FSH and LH

52
Q

hCG

A

placental hormone and LH agonist

53
Q

Urofollitropin

A

Purified FSH isolated from urine of postmenopausal women

54
Q

Follitropin

A

Recombinant form of human FSH

55
Q

Gonadotropin MOA

A

Replaces FSH and LH

56
Q

Gonadotropin indications

A

Ovulation induction in women with anovulation (hypogonadotropic hypogonadism, PCOS, obesity)
Controlled ovarian hyperstimulation in IVF
Infertility in male hypogonadotropic hypogonadism

57
Q

Gonadotropin Side Effects

A 
Ovarian hyperstimulation syndrome
Increase in multiple pregnancies
Increased risk of gynecomastia
Ovarian cancer
Ovarian cysts and hypertrophy
58
Q

Gonadotropin Contraindications

A

Any endocrine disorder other than anovulation
Primary gonadal failure
Pituitary tumor or sex-hormone dependent tumors
Ovarian cyst/enlargement
Pregnancy

59
Q

Gonadorelin (synthetic GnRH, short acting) MOA

A

“Pulsatile GnRH secretion”

Stimulates gonadotroph cells to produce and release LH and FSH

60
Q

Gonadorelin Indication

A

Mostly for diagnosis of hypogonadism
Stimulate ovulation
Infertility in men with hypothalamic hypogonadotropic hypogonadism

61
Q

Gonadorelin Side Effects

A

Anaphylaxis
Lightheadedness, flushing
Hypersensitivity dermatitis

62
Q

GnRH Agonist, Long acting

A

Goserelin, Histrelin, Leuprolide, Nadarelin, Triptorelin

63
Q

GnRH Agonist, Long acting MOA

A

Sustained, nonpulsatile administration of GnRH inhibits the release of FSH and LH, desensitizes GnRH receptors
1st transient increase in gonadal hormone levels (flare), then long lasting suppression of gonadotropins and gonadal hormones

64
Q

GnRH Agonist, Long acting, indication

A

Keep LH low in ovarian hyperstimulation for multiple mature oocytes for assisted repro tech (IVF)–> leuprolide, nafarelin

Endometriosis and uterine fibroids (leuprolide, nafarelin, goserelin)

Adjunct in prostate cancer (leupro, goserelin, histrelin, triptorelin)

Central precocious puberty (leupro, nafarelin)

Advancer breast and ovarian cancer, amenorrhea and infertility in women with PCOS

65
Q

GnRH Agonist, Long acting, side effects

A

hot flashes, sweats, headache (lack of estrogen, menopause)
osteoporosis
urogenital atrophy

66
Q

GnRH Agonist, Long acting, contraindications

A

Pregnancy

Breast feeding

67
Q

GnRH receptor antagonists

A

Ganirelix, Cetrorelix, Abarelix

68
Q

GnRH receptor antagonists MOA

A

Competitive antagonists of GnRH receptors
Inhibits secretion of FSH, LH
No flare effect

69
Q

Ganirelix and Cetrorelix indications

A

Keeps LH low in controlled ovarian hyperstimulation for assisted repro tech (IVF)

70
Q

Abarelix

A

Metastatic prostate cancer

71
Q

GnRH receptor antagonists side effects

A

Ovarian hyperstimulation syndrome
QT interval prolongation (abarelix)
Ectopic pregnancy, thrombotic disorder, spontaneous abortion (ganirelix)
Anaphylaxis (cetrorelix)

72
Q

Abarelix side effect

A

QT interval prolongation

73
Q

Ganirelix side effects (3)

A

Ectopic pregnancy, thrombotic disorder, spontaneous abortion

74
Q

Cetrorelix side effect

A

Anaphylaxis

75
Q

GnRH receptor antagonists Contraindications

A

Pregnancy, lactation, ovarian cysts or enlargement (not due to PCOS)
Primary ovarian failure
Thyroid of adrenal dysfunction
Vaginal bleeding of unknown etiology

76
Q

Which cells of the anterior pituitary produce and secrete prolactin?

A

Lactotrophs

77
Q

Prolactin release is inhibited by ____

A

dopamine secreted by hypothalamus

78
Q

Prolactin release is increased by

A

Thyrotropin-releasing hormone (TRH)

79
Q

Is there any negative feedback regulation on prolaction?

A

no- does not stimulate hormone secretion in target organ (mammary gland)

80
Q

What stimulates prolactin production during pregnancy?

A

Increasing estrogen levels

81
Q

What effect does estrogen have on prolactin during pregnancy?

A

Increases production but antagonizes its action, preventing lactations until after parturition

82
Q

What action is the powerful stimulus for prolactin release?

A

Suckling

83
Q

Physiological actions of prolaction

A

Regulates mammary gland development, milk protein biosynthesis and secretion

Increased prolactin inhibits GnRH release (suppresses ovulation during lactation)

84
Q

Causes of hyperprolactinemia

A

Rarely due to hypothalamic destruction

More commonly due to prolactin secreting adenomas

85
Q

Hyperprolactinemia produces

A

Amenorrhea, galactorrhea, and infertility in women
Loss of libido and infertility in men
If large tumor > visual changes due to compression of the optic nerves

86
Q

Dopamine Receptor Agonists

A

Bromocriptine, Cabergoline, Pergolide

Quinagolide (Europe)

87
Q

Treatment of prolactin deficiency

A

No preparation of prolactin is available to treat these patients

88
Q

Dopamine Receptor Agonists MOA

A

High affinity for dopamine D2 receptors

Inhibit pituitary prolactin release

89
Q

Dopamine Receptor Agonists Indications

A

Amenorrhea, galactorrhea, infertility from hyperprolactinemia, premenstrual syndrome (Bromocriptine, Cabergoline)

Acromegaly (high doses, helpful only if tumor secretes prolactin and GH, use in combo with Octreotide (Bromocriptine)

Parkinson’s Disease (Bromocriptine, Pergolide, Cabergoline)

90
Q

Dopamine Receptor Agonists Side Effects

A

Orthostatic hypotension
Cerebral vascular accident, seizure, acute MI (Bromo)
Arrhythmia, MI, heart failure (pergo)
Pulmonary fibrosis and pleural effusion (cabergo)

91
Q

Bromocriptine side effects

A

Cerebral vascular accident, seizure, acute MI

92
Q

Pergolide side effects

A

Arrhythmia, MI, heart failure

93
Q

Cabergoline side effects

A

Pulmonary fibrosis and pleural effusion

94
Q

Dopamine Receptor Agonists Contraindications

A

Hypersensitivity to ergot derivatives
Uncontrolled hypertension
Toxemia of pregnancy

95
Q

Which of the 3 dopamine receptor agonists causes less nausea?

A

Cabergoline

96
Q

How can you reduce nausea with the dopamine receptor agonists? What is the potential side effect?

A

Intravaginal administration

May cause local irritation

97
Q

What are the effects of dopamine receptor agonists and alcohol?

A

Alcohol intolerance may occur

98
Q

What is the concern with giving dopamine receptor agonists and a antihypertensive?

A

Coadministration can potentiate hypotension

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