Hypothalamic and Pituitary Pharmacology

Question 1

what increases GH release from the anterior piruitary

Answer 1

GHRH, exercise, hypoglycemia, dopamine, l-DOPA, arginine

Question 2

what is the treatment for patients who are growth hormone insensitive (receptor mutation) as in Laron dwarf

Answer 2

recombinant IGF-1 (Mecasermin)

Question 3

______ is a GHRH analog available for use in HIV patients with lipodystrophy secondary to use of highly active retroviral therapy (HAART) - reduces excess abdominal fat

Answer 3

Tesamorelin (Egrifta)

Question 4

what is the MOA of somatostatin

Answer 4

Inhibits GH release via GPCR coupled to Gi decreasing cAMP levels and activating K+ channels

Question 5

What is the MOA of GHRH

Answer 5

Rapidly stimulates GH synthesis and secretion via binding to GPCR coupled to Gs -> increasing cAMP and Ca++ levels in somatotrophs - no receptor down-regulation with continuous stimulation

Question 6

what are the Uses of Somatostatin Analogs

Answer 6

1) treat excess of growth hormon: Acromegaly, gigantism

2) To Control of bleeding from esophageal varices and GI hemorrhage

Question 7

What is Pegvisomant

Answer 7

GH receptor antagonist

Question 8

what are the side effects of somatostatins

Answer 8

1) transient hyperglycemia
2) Abdominal cramps and loose stools
3) cardiac (bradycardia, conduction disturbances)

Question 9

Prolactin release is under inhibitory control by _____

Answer 9

hypothalamic dopamine at D2 receptors

Question 10

The Main stimulus for prolactin release is ______

Answer 10

suckling - causes 10-100-fold increase within 30 min

Question 11

what are Cabergoline and Bromocriptine

Answer 11

Dopamine agonists used on the Tx of hyperprolactinemia

Question 12

which dopamine agonist is more effective in reducing prolactin secretion and Better tolerated

Answer 12

Cabergoline

Question 13

what is Desmopressin?

Answer 13

ADH analog

Question 14

what are the Renal actions of ADH

Answer 14

Mediated by V2 receptors (GPCRs coupled to Gs)
Increases the rate of insertion of water channels (aquaporins) into luminal membrane -> increased water permeability -> leading to an antidiuretic effect

Question 15

what is the treatment of choice for Central Diabetes Insipidus

Answer 15

Desmopressin

Question 16

What is Chlorpropamide

Answer 16

1st generation sulfonylurea, that can be used in the treatment of ADH defieciency.
• Potentiates action of small or residual amounts of ADH - mechanism not clear
• Option for patients intolerant (side effects-allergy) to desmopressin

Question 17

what are the causes of drug induced Nephrogenic diabetes insipidis

Answer 17

• Lithium: reduces V2-receptor mediated stimulation of adenylyl cyclase. As many as 1/3 of patients treated with Li+ may develop nephrogenic diabetes insipidus
• Demeclocyline (tetracycline antibiotic): mechanism not completely understood but possibly acts via block of ADH binding to receptor

Question 18

what is the treatment for Nephrogenic Diabetes Insipidus

Answer 18

• Thiazide diuretics: Paradoxically reduce the polyuria of patients with DI. Mechanism not completely understood but antidiuretic effect parallels ability to cause natriuresis - used in doses that mobilize edema fluid.
• NSAIDs: Since prostaglandins attenuate ADH-induced antidiuresis, inhibition of PG synthesis by indomethacin may relate to the antidiuretic response seen. Indomethacin has greatest efficacy among NSAIDs.

Question 19

what is the Treatment of hyponatremia seen in SIADH

Answer 19

1) Restriction of free water intake is initial conservative approach
2) Demeclocyline inhibits ADH effect on distal tubule and has been preferred drug in patients with inadequate response to conservative measures
3) V2 receptor antagonist - potential therapeutic advance for hyponatremia (also tried in HF).
Tolvaptan (Samsca®) - oral route, expensive
Conivaptan (Vaprisol®) - IV infusion (useful in hospitalized SIADH patients) - if severe symptomatic hyponatremia present, conivaptan can be given with hypertonic saline (3%), permitting a more rapid initial correction

Question 20

too rapid correction of hyponatremia can cause _____

Answer 20

cerebellar pontine myelinolysis

Question 21

Von Willebrand’s disease and moderate hemophilia A can be treated by _____

Answer 21

IV desmopressin, (elevates von Willebrand factor,

elevates factor VIII)

Question 22

nocturnal enuresis can be treated with ____

Answer 22

oral desmopressin