Intro to Endocrine Pharmacology

Question 1

Prolactin Regulation

Answer 1

• Prolactin secretion is tonically inhibited by dopamine released from neurons in the median eminence of the hypothalamus.
• Release is stimulated by physical/emotional stress, suckling, phenothiazines (DA antagonists), TRH.
• No clinical use for Prolactin.

Question 2

Bromocriptine, Cabergoline

Answer 2

1. DA agonists-dec prolactin release
2. Tx:
   - Prevent breast tenderness/engorgement and inhibit lactation.
   - Tx of amenorrhea and galactorrheaassociated w/hyperprolactinemia due to pituitary adenomas.
   - Dec GH secretion for GH-secreting adenomas.
3. Cabergoline is preferred due to longer t1/2 (admin 2x/week), better efficacy, and less SE.
4. SE:
   - nausea, light-headedness,
   - orthostatic hypotension, and fatigue
   - psychiatric disturbances
   - erythromelalgia.
5. CI: Don’t use in pregnant unless used to control prolactin-secreting tumors.

Question 3

Somatropin, Somatrem

Answer 3

1. GH agonists
2. indications:
   - Tx growth failure due to: GH deficiency, chronic renal disease, Turner’s syndrome.
   - Cachexia in AIDS
   - Improving metabolic state/inc lean body mass
   - sense of well-being in deficient state
   - Improved GI function in short bowel syndrome.
3. SC or IM injections, typically daily in the evenings.
4. SE:
   - Injection site rxns
   - fluid retention/edema (reduces w/tx time)
   - inc intracranial pressure (rare)
   - musculoskeletal pain/stiffness,
   - hyperglycemia/hypoglycemia/hypothyroidism, glycosuria.
5. CI:
   - Acute critical illness (post heart/abdominal surgery),
   - acute respiratory insufficiency,
   - caution in DM, hypothyroidism, dont give w/in 1 year of tx for leukemia.

Question 4

Sermorelin

Answer 4

1. Synthetic GHRH approved for tx of GH deficiency, not as effective as GH therapy. Used diagnostically to determine origin of GH deficiency (hypo vs pit).

Question 5

Mecasermin, Mecasermin rinfabate

Answer 5

1. Mecasermin recombinant human IGF-1, Mecasermin rinfabate is a mix of rhIGF-1 and IGF binding protein 3 (inc t1/2 of IGF-1). Not as effective as GH therapy.
2. Indications:
   - Mecasermin rinfabate not FDA approved for anything (still used sometimes though).
   - Mecasermin used in pts unresponsive to GH therapy: IGF-1 mutation/deletion, GH receptor mutation, GH abs.
3. Mecasermin injected SC 2x/day, mecasermin rinfabate SC 1x/day.
4. SE:
   - Mecasermin has high incidence of hypoglycemia and cellular proliferation because it is unbound.
   - Other SE similar to GH therapy.
5. CI: similar to other GH therapy.

Question 6

Octrotide, Lanreotide

Answer 6

1. GH antagonists, somatostatin analongs.
2. • Inhibt secretion of both pitutitary and GI hormones (5HT, gastrin, VIP, insulin, glucagon, secretin, motilin, pancreatic polypeptide, GH, thyrotropin).
   • Inc intestinal absorption of water and electrolytes
   • dec pancreatic and gastric acid secretions, and inc intestinal transit time.
3. Indications
   - Tx for GH excess (acromegaly) or other hormone secreting tumors (VIP/carcinoid tumors)
   - reduce tumor size/growth
   - tx excessive diarrhea.
4. Injected SC 3x/day (long acting 1x/mon available), lanreotide is 1x/mon. t1/2 in serum 90 min, activity for 9hrs.
5. SE: GI effects common but subtle, gallstones and gallbladder sludge, cardiac problems
6. CI: gall bladder disease, DM, cardiac disease, thyroid problems.

Question 7

Pegvisomant

Answer 7

1. GH receptor antagonist
2. Tx for GH excess syndromes, Return to normal IGF-1 levels in 97% of pts.
3. Injected SC 1x/day
4. SE: growth of GH secreting tumor (lack of negative feedback). Reversible hepatotoxicity.
5. CI: hepatic disease