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Pharmacology Test #5 > Pharmacology of Anterior Pituitary Hormones > Flashcards

Pharmacology of Anterior Pituitary Hormones Flashcards

1
Q

Three groups that the hormones of the anterior-pituitary can be classified into

A
  1. Somatotropic hormones (growth hormone, prolactin)
  2. Glycoprotein hormones (LH, FSH, TSH)
  3. Pro-opiomelanocortin peptides (ACTH)
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2
Q

Five different hormone-producing cell types that have been identified in the anterior pituitary

A
  1. Somatotroph
  2. Lactotroph (Mammotroph)
  3. Thyrotroph
  4. Gonadotroph
  5. Corticotroph-lipotroph
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3
Q

thyroid hypofunction

A

very sensitive to cold; lack of sweating; reduced rate of metabolism; poor accumulation of radioiodine by thyroid

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4
Q

adrenal deficiency (may result in death)

A

sensitivity to physical stress; increased rate of infection; frequent episodes of collapse

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5
Q

In children, hypopituitarism (hypopituitary dwarfism) is usually the result of

A

failure of pituitary to develop normally during embryonic life

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6
Q

Is the hypopituitary dwarf mentally retarded?

A

No

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7
Q

What can help differentiate hypopituitary dwarfism from other types of dwarfism?

A

the responsiveness of thyroid and adrenal glands to stimulation by trophic hormones

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8
Q

Important feature of acromegaly

A

excessive growth hormone secretion (by pituitary tumor)

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9
Q

Characteristic of Cushing’s syndrome

A

oversecretion of ACTH

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10
Q

Increased secretion of prolactin in women leads to

A

amenorrhea, galactorrhea, and infertility

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11
Q

Increased secretion of prolactin in men leads to

A

impotence

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12
Q

Hypersecretion of gonadotrophins can result in what in children?

A

can result in precocious sexual development in children

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13
Q

Disorders and dysfunctions of target organs such as gonads, thyroid gland, adrenal gland can lead to

A

the release of pituitary from the negative feedback control and results in excessive secretion of various pituitary hormones

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14
Q

Most abundant active agent synthesized in the anterior pituitary

A

Growth hormone

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15
Q

Stimulation of growth hormone secretion

A

glucose decrease, FFA decrease, aa increase (arginine); fasting; prolonged caloric deprivation; stage IV sleep; exercise; stress; insulin-induced hypoglycemia etc.

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16
Q

Inhibition of growth hormone secretion

A

somatostatin; glucose increase; FFA increase; somatomedins; growth hormone; beta-agonists; cortisol; obesity; pregnancy; old age

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17
Q

Growth hormones causes

A

proportional increase in size (growth) of almost all organs in the body; it leads to increase in weight - cell proliferation rather than hypertrophy

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18
Q

In hypopituitary dwarfs, administration of human growth hormones results in

A

proportionate growth as in normal individuals

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19
Q

Gonadal steroids promote

A

epiphysial fusion

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20
Q

Abnormal growth of hypopituitary dwarfs with continuous GH administration

A

long limbs and short trunk

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21
Q

Preparations of growth hormone

A

Somatropin; Somatrem; Nutropin Depot;

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22
Q

Somatropin

A

Humatrope; Serotism; Genotropin, Nutropin, Saizen

recombinant GH injected SC in evening; weakly antigenic; reaches peak levels 2-4 hrs after injection

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23
Q

Somatrem

A

Protropin:

recombinant methionyl-growth hormone injected SC in evening; more antigenic than somatropin

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24
Q

Nutropin Depot

A

encapsulated form of somatropin for intramuscular injection once or twice per month

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25
Q

Absorption, fate and excretion of growth hormone

A

absorbed well following adminstration; maximal concentrations achieved within 2-6 hours; removed largely by liver and kidney; half-life of clearance is 15 to 30 minutes

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26
Q

Describe the GH receptor

A

monomer with a single membrane spanning domain that lacks intrinsic tyrosine kinase activity; dimerizes upon binding growth hormone

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27
Q

Dimerization of GH results in

A

the recruitment and activation of the JAK proteins which catalyze the phosphorylation and activation of PI-3 kinase, STAT, and MAPK signaling pathways

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28
Q

GH induces the production of

A

insulin-like growth factors (IGFs) known as somatomedins in the liver

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29
Q

Primary source of circulating IGFs

A

liver

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30
Q

Primary mediator of the actions of growth hormone

A

IGF-1

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31
Q

Type 1 IGF receptor binds

A

both IGF-1 and IGF-2 with high affinity

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32
Q

Type II IGF receptor binds

A

IGF-2 specifically

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33
Q

Type II IGF receptor signals

A

the encoding of cytoplasmic proteins that act as receptor for proteins targeted to lysosomes

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34
Q

In plasma and other body fluids, IGFs are tightly bound to

A

large protein carriers, the IGF-binding proteins (IGFBPs)

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35
Q

Characteristics of severe growth hormone deficiency

A
  1. short stature and mild adiposity
  2. adiposity and hypoglycemia
  3. predicted adult height substantially below mean parental height
  4. adnormally slow growth velocity
  5. abnormally low plasma concentrations of IGF-1
  6. poor responses to provocative tests for secretion of GH
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36
Q

To diagnose GH deficiency:

A
  1. Exclude all other causes of poor growth
  2. Growth rate below 4 cm/year
  3. Perform provocative test
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37
Q

What is a provocative GH test?

A

Administer stimuli such as insulin-induced hypoglycemia, levodopa, apomorphine, agonists of serotonin and measure plasma growth hormone within 45-90 minutes - GH level of less than standard conc. indicates deficiency

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38
Q

GH replacement therapy is approved in

A

children with idiopathic short stature (non-hormone deficient short stature) with a height that is 2.25 deviations or more below national norm for children of same age

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39
Q

GH is approved for children with what condition

A

chronic renal failure

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40
Q

What does GH do in children with Prader-Willi syndrome (characterized by growth failure, low muscle tone and obesity)?

A

growth hormone therapy decreased body fat and increased lean body mass

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41
Q

Adults with growth hormone deficiency have

A

generalized obesity, reduced muscle mass, and reduced cardiac output

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42
Q

Other weird uses of growth hormone

A

AIDS-associated wasting and patients with short bowel syndrome dependent on TPN

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43
Q

Rapid growth with GH may cause

A

scoliosis in a few patients

44
Q

Rare side effect of GH in children

A

intracranial hypertension, visual changes, headache and nausea

45
Q

Side effects of GH in adults

A

peripheral edema, athralgias, carpal tunnel syndrome, myalgias, mild to moderate nausea and headache

46
Q

What happens with GH treatment of critically ill patients

A

increases mortality

47
Q

Mecasermin (Increlex)

A

recombinant human IGF-1

48
Q

Mecasermine rinfabate (Iplex)

A

recombinant human IGF-1/IGFBP-3

49
Q

Laron-type dwarfism

A

inheritable growth hormone resistant disease:

receptors for GH are few or absent; plasma level of biologically active GH high; low plasma IGF-1

50
Q

IGF-1 deficient patients (Laron-type dwarfs) responds well to

A

Mecasermin therapy

51
Q

Majority of acromegaly cases are caused by

A

growth-hormone secreted from pituitary tumors referred to as somatotrophinomas

52
Q

In patients with non-fused ephiphysis, growth hormone excess causes

A

enhanced longtitudinal growth and gigantism

53
Q

In adults, growth hormone excess causes

A

acromegaly with symptoms such as arthropathy, carpal tunnel syndrome, generalized visceromegaly, hypertension, headache, lethargy, excess perspiration and sleep apnea

54
Q

Treatment of Acromegaly:

A
  1. Growth hormone secreting pituitary tumors are treated with surgery or irradiation
  2. If growth hormone hypersecretion persists, use somatostatin analogs, dopamine receptor agonists, growth hormone antagonists
55
Q

Somatostatin analogs

A
  1. Octreotide (Sandostatin)
  2. Lanreotide (Somatuline)
  3. Vapreotide
  4. Pasireotide (Signifor)
56
Q

Agonists of dopamine are potent inhibitors of

A

lactotroph function

57
Q

Dopamine agonists

A

ergot derivative such as 2-bromo-ergocrypine (bromocriptine; Parlodel), carbegoline (Dostinex)

58
Q

How can a dopamine agonist inhibit growth hormone secretion by pituitary tumor cells

A

if the growth hormone secreting tumor cells originate from lactotrophs (prolactin secreting pituitary cells)

59
Q

Pegvisomant (Somavert)

A

growth hormone antagonist developed by recombinant DNA technology for the treatment of acromegaly

60
Q

Prolactin is synthesized and stored in

A

pituitary cells called lactotrophs;

also synthesized by human placental tissue

61
Q

Stimulation of prolactin release

A

pregnancy; estrogen; nursing; sleep; stress; low glucose; dopamine antagonists; opioids; serotonin; H2 antagonists

62
Q

Inhibition of prolactin release

A

dopamine; somatostatin; GnRH-associated peptide; prolactin; GABA; high glucose

63
Q

Describe the prolactin receptor

A

monomer that lacks intrinsic tyrosine kinase activity; binding of prolactin causes receptor dimerization resulting in the recruitment and activation of JAK kinases that phosphorylate JAK proteins and eventually the activation of transcription factor STAT proteins

64
Q

Which hormones bind prolactin receptors

A

prolactin, growth hormone and placental lactogen

65
Q

Half life of natural prolactin

A

15 - 20 minutes

66
Q

Preparations for treating prolactin-deficient patients

A

there is currently no appropriate preparation available

67
Q

Hyperprolactinemia may occur

A
  1. as a result of various drugs (antagonists of dopamine)
  2. due to disorders of hypothalamus or pituitary gland that interfere with the action of prolactin release inhibiting hormone
  3. prolactin secreting pituitary tumors
68
Q

Treatment of hyperprolactinemia

A
  1. irradiation and surgical removal of tumor

2. prolactin-secreting tumors are treated with dopamine agonists

69
Q

Dopamine agonists used to treat prolactin secreting tumors

A

quinagolide (Norprolac);
ergot derivative such as bromocriptine (Parlodel);
cabergoline (Dostinex, Cabaser)

70
Q

How do dopamine agonists used to treat prolactin secreting tumors work?

A

They activate the dopaminergic (D2) receptors that are cupled to the inhibition of prolactin release in the normal anterior pituitary gland. This dopamine-inhibitor pathway is retained by prolactin-secreting pituitary tumor cells.

71
Q

Pharmacokinetics of dopamine agonists

A

administered orally and circulate bound to albumin; metabolized and excreted primarily in feces (bile)

72
Q

Toxicity and contraindications of dopamine agonists

A
  1. Some patients experience nausea, headache, fatigue with dopamine agonist treatment
  2. Nausea occurs less often with carbegoline than with bromocriptine treatment
73
Q

Gonadotropic hormones

A

Follicle-stimulating hormone (FSH), Luteinizing hormone (LH)

74
Q

Describe the structure of glycoprotein hormones of the anterior pituitary

A

heterodimers containing alpha and beta subunits; alpha units are identical

75
Q

LH and FSH levels during the menstrual cycle

A

Plasma LH and FSH levels are highest near the time of ovulation; plasma LH and FSH levels are also high after menopause

76
Q

Secretion of chorionic gonadotropin (CG)

A

CG is produced during pregnancy by fetal placenta (syncytiotrophoblaslts); enters the maternal blood and supports luteal function

77
Q

Gonadotropic hormones (pituitary and placenta derived) are effective only when given by

A

injection (intramuscular and subQ)

78
Q

Chorionic gonadotropin for injection

A

Pregnyl; Profasi; A.P.L.

79
Q

How is chorionic gonadotropin hormone used clinically?

A

used to treat infertility in women (administer pregnyl after a series of treatments with menotropins)

80
Q

Menotropins for injection

A

Menopur, Pergonal, Humegon, Repronex

81
Q

Clinical use of menotropins

A

used to treat infertility in women; give low doses of pergonal daily for 7 to 12 days; give a high dose of CG preparation

82
Q

Urofollitropin for injection

A

Metrodin, uFSH, Fortinex, Bravelle

83
Q

Activity of CG

A

contains LH activity

84
Q

Activity of Menotropins

A

contains both LH and FSH activity

85
Q

Activity or Urofollitropin

A

contains only FSH activity

86
Q

Use of Urofollitropin

A

exactly the same as menotropins

87
Q

Recombinant human FSH preparations

A

follitropin-alpha (Gonal-F) and follitropin - beta (Puregon, Follistim)

88
Q

Recombinant human LH preparations

A

rhLH; Lutropin alfa; Luveris

89
Q

Recombinant human LH approved for use in

A

in women with LH deficiency - in combination with follitropin-alpha

90
Q

Recombinant Human Chorionic Gonadotropin (rhCG)

A

choriogonadotropin alfa (Ovidrel)

91
Q

Therapeutic uses for Gonadotropin preparations

A

Female infertility
In vitro fertilization
Male infertility

92
Q

Diagnostic uses of gonadotropins

A
  1. Pregnancy diagnosis and prediction of ovulations

2. Diagnoses of diseases of reproductive systems in both males and females

93
Q

Low levels of LH and FSH can indicate

A

hypogonadotropic hypogonadism

94
Q

High levels of LH and FSH can indicate

A

gonadal failure

95
Q

Menopausal gonadotropins can cause

A

ovarian hyperstimulation/enlargement

96
Q

Secretion of TSH

A

produced in the pituitary thyrotroph

97
Q

Regulation of TSH secretion

A

synthesis and secretion is stimulated by TRH; circulating thyroid hormones exert negative feedback on TSH

98
Q

Preparation of TSH

A

Thyrogen (also known as thyrotropin alpha)

99
Q

MOA of TSH preparations

A

Thyrogen binds to TSH receptor on normal thyroid and differentiated thyroid cancer cells and stimulates cAMP production. cAMP activates a number of steps in the thyroid hormone synthetic pathways

100
Q

Uses of Thyrogen

A

for tests involved in (131)I uptake by residual thyroid gland (post-operative) and metastasized thyroid carcinoma

101
Q

Growth Hormone Analogs

A
  1. Somatropin (Humatrope, Serotism, Genotropin, Nutropin, Saizen)
  2. Somatrem (Protropin)
  3. Nutropin Depot
  4. Sermorelin acetate (Geref)
  5. Mecasermine rinfabate (Iplex)
  6. Mecasermin (Increlex)
102
Q

Growth Hormone Antagonists

A
  1. Lanreotide (Somatuline) - somatostatin analog
  2. Octreotide (generic, Sandostatin) - somatostatin analog
  3. Pasireotide (Signifor LAR) - somatostatin analog
  4. Pegvisomant (Somavert)
103
Q

Thyroid stimulating hormone analog

A

Thyrotropin, recombinant human TSH (Thyrogen, Thyrotropin alfa)

104
Q

Gonadotropin Analogs

A
  1. Menotropins [hMG] (Menopur, Pergonal, Humegon, Repronex)
  2. Chorionic gonadotropin for injection [hCG] (Pregnyl; Profasi; A.P.L.)
  3. Urofollitropin (Bravelle, Metrodin, uFSH, Fortinex)
  4. Follitropin-alpha (Gonal-F)
  5. Follitropin-beta (Puregon, Follistim)
  6. Lutropin alfa [rhLH] (Luveris)
  7. Choriogonadotropin alfa (Ovidrel)
105
Q

Gonadotropin-Releasing Hormone Analogs

A
  1. Gonadorelin hydrochloride [GnRH] (Lutrepulse; Factrel)
  2. Leuprolide acetate (Lupron, Eligard)
  3. Histrelin acetate (Supprelin LA, Vantas)
  4. Nafarelin acetate (Synarel)
  5. Goserelin acetate (Zoladex)
  6. Triptorelin pamoate (Trelstar)
106
Q

Gonadotropin-Releasing Hormone Antagonists

A
  1. Ganirelix (Antagon, Orgalutran)
  2. Cetrorelix (Cetrotide)
  3. Abarelix (Plenaxis)
  4. Degarelix (Fimagon)
107
Q

Prolactin Antagonists (Dopamine agonists)

A
  1. Bromocriptine (Parlodel)

2. Carbegoline (Dostinex)

Pharmacology Test #5 (11 decks)

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