Intro to Reproductive Axis Flashcards Preview

My DEMS 4 > Intro to Reproductive Axis > Flashcards

Flashcards in Intro to Reproductive Axis Deck (23):
1

Control of Anterior pituitary hormone release

Release of hypothalamic hormones under CNS control via NTs

Release of anterior pituitary hormones (trophic hormones) controlled by hypothalamic hormones.
-Then delivered via portal circulation to the pituitary gland for release into the sytemic circ where they act on endocrine glands to regulate production of hormones that perform ultimate regulatory functions.

2

Control of posterior pituitary hormone release

Synthesized in peptidergic neurons in the hypothalamus and then transported to the neuronal terminal in the posterior lobe of pituitary

Neuronally released into the systemic circulation and act directly on target tissues to perform regulatory functions

3

Growth hormone (pharm analogs)

Somatropin
Somatrem (no longer available)
t1/2 25 mins
IM
peak 2-4 hrs
Active levels persist 36 hrs

4

Pharmacodynamics of GH

-release increased by GHRH, exercise, hypoglycemia, dopamine, L-DOPA, arginine

Decreased by somatostatin

At pharm doses, GH works indirectly to stimulate synthesis of insulin like growth factors (IGF-1, IGF-2) promoting linear and skel muscle growth

5

GH replacement therapy in kids

Daily at bedtime via SC injection (more effective, mimics natural release pattern) or 3 times a week IM

6

What if kid is growth hormone insensitive?

-can treat with recombinant IGF-1
-concern with hypoglycemia (take carbs before)

7

Uses of GH (FDA approved)

-poor growth from Turner’s syndrome, Prader-Willi syndrome, and chronic renal insufficiency

Growth hormone deficiency in adults (pit tumor)

Treatment of wasting or cachexia in AIDS patients

Patients with short bowel syndrome dependent on total parenteral nutrition

8

Illicit uses of GH

-athletes to increase muscle mass, improve performance (lack of evidence)

-healthy adults for "anti-aging" effects
small changes in body composition and increased rates of adverse events

off label use is ILLLEGAL

9

Side effects of GH (somatropin)

-generally safe for kids
-insulin resistance and glucose intolerance may occur
-Slight increased risk for idiopathic intracranial hypertension (pseudotumor cerebri)
-Rarely pancreatitis, gynecomastia, nevus growth
•Misuse in athletes: Acromegaly, arthropathy, visceromegaly, extremity enlargement

10

GHRH

Rapidly stimulates GH synthesis and secretion via binding to GPCR coupled to Gs

-Note: Ghrelin stimulate GH release via a different GPCR

-Dominant inhibitory regulator is Somatostatin
-GH also acts as own feedback inhibitor.

11

GHRH analogs

Sermorelin (not on market)
Tesamorelin for HIV pts

12

Somatostatin

-Inhibits GH release via GPCR Gi decreasin cAMP levels, activating K+ channels
-reduces insulin and glucagon release
-interferes with TRH ability to release TSH

13

Somatostatin and analogs pharmacokinetics

Somatostatin: t1/2 3-4 mins limiting usefulness

Octreotide: t/12 90mins, SC every 6-12 h
Octreotide (Somatostatin LAR depot): IM every 4 weeks
Lanreotide given SQ every 4 weeks

14

Uses of Somatostatin analogs

Pituitary: excess GH
-acromegaly
-gigantism
But for adenoma: surgical resection preferred
-For pharm, though, long acting somatostatin analog is preferred
-Dopamine agonists may inhibit GH secretion in some pts. Cabergoline as adjuvant therapy for acromegaly (oral)
-GH receptor antag: Pegvisomant (SQ dose daily)

Non Pituitary:
Control of bleeding from esophageal varices and GI hemorrhage (constrict splanchnic arterioles)

15

Dopamine agonists

-inhibition of GH secretion (Cabergoline)
-hyperprolactinemia (decreases secretion and tumor size with D2 agonist)

16

Pegvisomant

-GH receptor antagonist

17

Prolactin

-release under inhibitory control by hypothalamic dopamine at D2 receptors.
-main stim for release is suckling
-stimulates milk production

18

Hyperprolactinemia (prolactinomas)

-respond to dopamine agonists that decrease secretion and reduce tumor size.
-oral

19

bromocriptine

-D2 and D1 agonist
SE: n/v, HA, postural hypotension, less frequently can see psychosis or insomnia

20

Cabergoline

preferred agent for hyperprolactineia
-more selective for D2 and more effective in reducing prolactin secretion
-better tolerated (less nausea), but hypotension and dizziness

21

Vasopressin

aka anti-diuretic hormone
-parenteral admin
t1/2 20 mins

22

Desmopressin

ADH analog, but t1/2 1.5-2 hrs

23

Pharmacodynamics of ADH

-control water content throughout body
-action on distal nephron and collecting tubules of kidney
-Main stimulus for release? rising blood osmolality
-also: stimulate by decrease in circulating blood volume
-release inhibited by alcohol