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MHD2/Pharm - Endocrine > Pharm - Hypothalamic & Pituitary > Flashcards

Pharm - Hypothalamic & Pituitary Flashcards

1
Q

How do the connections between the hypothalamus and the anterior and posterior pituitary differ?

A

The hypothalamus communicates with the anterior pituitary via vascular supply, whereas it communicates with the posterior pituitary via axonal projections

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2
Q

Describe how the control and action of prolactin is different than the other Hypothalamic/Pituitary hormones

A

Prolactin does not have a corresponding releasing hormone from the hypothalamus like the other hormones does. Prolactin acts directly on target tissues instead of stimulating hormone release from a peripheral gland.

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3
Q

What are the 5 endocrine axes?

A 
HPL: growth hormone
HPT: thyroid stimulating hormone
HPA: ACTH
HPG: LH and FSH
Prolactin
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4
Q

Which hormones act through a JAK/STAT pathway?

A

Prolactin and Growth hormone

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5
Q

Describe the feedback that tightly regulates most hypothalamic/pituitary hormones

A

End products cause negative feedback through long, short, and ultrashort loops. This feedback shuts down the axes in order to maintain stable levels of hormones.

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6
Q

How does GH affect muscle and fat?

A

GH is anabolic on muscles and catabolic on fat

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7
Q

What hypothalamic hormones regulate GH?

A

GHRH causes GH release and somatostatin inhibits GH release

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8
Q

What is the effect of GH in childhood?

A

Linear growth, growth of long bones, cartilage, muscle, and organ systems

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9
Q

What are the effects of GH in adulthood?

A

Protein synthesis, bone density
Lipolysis
Glucose release, reduced insulin sensitivity

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10
Q

What enzyme mediates most of the effects of GH?

A

IGF-1

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11
Q

Characteristics of child with GH deficiency

A

Short stature, adiposity, hypoglycemia (due to hyperinsulinemia)

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12
Q

Characteristics of adult with GH deficiency

A

Increased adiposity, decreased muscle mass
Decreased bone mass
Cardiac muscle atrophy, atherogenic lipid profile
Overall malaise

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13
Q

What is Sermorelin?

A

Synthetic GHRH

Used when pituitary has normal function, defect in GHRH/hypothalamus

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14
Q

What are Somatropin and Somatrem?

A

Synthetic GH

Works as long as IGF-1 function is intact

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15
Q

What is Mecasermin?

A

Synthetic IGF-1

Used when defect is in GH receptor or there are antibodies against GH

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16
Q

How does the structure of Somatropin and Somatrem differ from GH?

A

Somatropin is identical to GH

Somatrem has an extra methionine at the N-terminus

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17
Q

What pediatric conditions are treated with recombinant human growth hormone (Somatropin/Somatrem)?

A 
GH deficiency
Chronic renal failure
Prader-Willi
Turner syndrome
Idiopathic short stature
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18
Q

What adult conditions are treated with recombinant human growth hormone (Somatropin/Somatrem)?

A

GH deficiency
AIDS associated wasting
Short bowel syndrome

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19
Q

What side effects are associated with recombinant human growth hormone (Somatropin/Somatrem)?

A 
Neoplasms: Leukemia, melanocytic lesions
Hypothyroidism
Insulin resistance
Arthralgias
Induces CYP450 enzymes
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20
Q

What are the contraindications for recombinant human growth hormone (Somatropin/Somatrem)?

A

Pediatric patients with closed epiphyses
Active underlying intracranial lesion
Active malignancy
Proliferative diabetic retinopathy

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21
Q

What conditions are associated with GH excess?

A

In children: Gigantism (excessive long bone growth)

In adults: Acromegaly (growth of cartilagenous and deep organs)

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22
Q

What diseases are patients with acromegaly at high risk for?

A

CV disease
GI disease
GI cancers
Reproductive disorders

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23
Q

What are the treatment options for pituitary adenoma?

A

Surgical removal

Medical management with somatostatin analogues, GH receptor antagonists or dopamine agonists

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24
Q

What drugs are somatostatin analogues?

A

Octreotide
Lanreotide
*These drugs inhibit GH secretion from the pituitary

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25
Q

What is the GH receptor antagonist?

A

Pegvisomant

26
Q

What dopamine receptor agnonist is used for acromegaly treatment?

A

Bromocriptine

27
Q

What conditions are treated with somatostatin analogues (Octreotide/Lanreotide)?

A

Pituitary adenoma/Acromegaly
Carcinoid crisis
Secretory diarrhea due to VIPoma
Control acute GI bleed (varices)

28
Q

What are the side effects of somatostatin analogues (Octreotide/Lanreotide)?

A

Nausea, vomiting, cramps, GI discomfort
Sinus bradycardia, conduction abnormalities
Hypoglycemia
Gallstones

29
Q

What drug-drug interactions occur with octreotide?

A

Octreotide decreases cyclosporin levels and increases bromocriptine levels

30
Q

Describe the mechanism of action of Pegvisomant

A

Binds to GH receptors and prevents the dimerization the initiates the signaling cascade and thus blocking the action of GH

31
Q

What is the indication for Pegvisomant?

A

Treatment refractory acromegaly

32
Q

What are the side effects of Pegvisomant?

A

Increases pituitary adenoma size

Increases liver enzymes

33
Q

What are the two gonadotropins?

A 
Leutinizing hormone (LH)
Follicle stimulating hormone (FSH)
34
Q

In women, what is the main function of LH and FSH?

A

LH stimulates thecal cells to produce androgens. FSH stimulates granulosa cells to convert the androgens to estrogens.

35
Q

What are the pharmacological gonadotropins?

A

Human menopausal gonadotropin/menotropin
Human chorionic gonadotropin
Urofollitropin
Follitropin

36
Q

What analog of GnRH is used pharmacologically?

A

Gonadorelin

37
Q

How is the gonadal axis inhibited?

A

Long acting GnRH analogues

GnRH antagonists

38
Q

What are the long acting GnRH analogues?

A

Goserelin, Histrelin, Leuprolide, Nafarelin, and Triptorelin

39
Q

What are the GnRH receptor antagonists?

A

Ganirelix
Centrorelix
Abarelix

40
Q

What are the indications for the Gonadotropins?

A

Ovulation induction for hypogonadotropic hypogonadism, PCOS, obesity
Ovarian hyperstimulation for IVF

41
Q

What is ovarian hyperstimulation syndrome?

A

Ovarian enlargement, ascites, hydrothorax, hypovolemia and potential shock due to treatment with gonadotropins

42
Q

What are the side effects of gonadotropin therapy?

A 
Ovarian hyperstimulation syndrome
Multiple pregnancies
Gynecomastia in men
Ovarian cancer
Ovarian cysts and hypertrophy
43
Q

What are contraindications of gonadotropin therapy?

A 
Endocrine disorders
Primary gonadal failure
Pituitary or sex hormone dependent tumors
Ovarian cyst
Pregnancy
44
Q

What are the indications of gonadorelin?

A

Diagnosis of hypogonadism
Stimulate ovulation
Infertility in men (Hypogonadotropic hypogonadism)

45
Q

What are the side effects of gonadorelin?

A

Anaphylaxis with multiple administrations
Lightheadedness & flushing
Hypersensitivity dermatitis

46
Q

How do long acting GnRH analogs inhibit the gonadal axis?

A

Nonpulsatile GnRH inhibits the release of LH and FSH by desensitizing the GnRH receptors in the pituitary

47
Q

Indication for sustained GnRH analogs

A

IVF: keep LH surge low to provide multiple mature oocytes
Endometriosis and uterine fibroids
Prostate cancer adjuvant
Central precocious puberty

48
Q

Side effects of sustained GnRH analog treatment

A

Hotflashes, sweats, headache
Osteoporosis
Urogenital atrophy

49
Q

Contraindications of sustained GnRH analog treatment

A

Pregnancy/Breast feeding

Hypersensitivity

50
Q

What is the biphasic effect of GnRH analog treatment?

A

First there is a flare of increased FSH and LH due to agonist effect, this is followed by a long lasting suppression of the entire axis.

51
Q

What is one advantage of GnRH receptor antagonists compared with the sustained GnRH analog therapy?

A

Antagonists do not have the flare effect that is associated with the long acting GnRH analogues.

52
Q

What are the indications for GnRH receptor antagonists?

A

Ganirelix and Cetrorelix are used for IVF controlled ovarian stimulation
Abarelix is used for metastatic prostate cancer

53
Q

What are the side effects of GnRH receptor antagonists?

A

Ovarian hyperstimulation
QT prolongation (Abarelix)
Ectopic pregnancy, thrombotic disorder, spontaneous abortion (Ganirelix)
Anaphylaxis (Cetrorelix)

54
Q

What are the contraindications for GnRH receptor antagonists?

A

Pregnancy, lactation, ovarian cysts (not from PCOS)
Primary ovarian failure
Thyroid/adrenal dysfunction
Vaginal bleeding of unknown etiology

55
Q

What controls prolactin release?

A

Dopamine tonically inhibits prolactin release
Prolactin release is increased by TRH
There is no negative feedback regulation

56
Q

What is the physiologic role of prolactin?

A

Mammary gland development and milk biosynthesis

Inhibits GnRH release (suppresses ovulation during lactation)

57
Q

Presentation of hyperprolactinemia

A

Amenorrhea, galactorrhea and infertility in women

Loss of libido and infertility in men

58
Q

What drugs are used to treat hyperprolactinemia?

A

Dopamine agonists: Bromocriptine, Cabergoline, Pergolide

59
Q

How is prolactin deficiency treated?

A

No currently available treatments

60
Q

Side effects of dopamine agonists

A

Orthostatic hypotension
Cerebrovascular accident, seizure, MI (bromocriptine)
Arrhythmia, MI, heart failure (Pergolide)
Pulmonary fibrosis and pleural effusion (Cabergolide)

MHD2/Pharm - Endocrine (7 decks)

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