Pituitary Pharmacology - Self Study

Question 1

What is one strange drug used to increase aqueous humor outflow via blocking production of prostaglandins? Is it fast enough for acute attacks?

Answer 1

Epinephrine - no

Question 2

What are the ophthalmic beta blockers?

Answer 2

timolol, carteolol, betaxolol

Question 3

What are the two most commonly used alpha-2 agonists to decrease aqueous humor production?

Answer 3

Brimonidine, apraclonidine

Question 4

What are the carbonic anhydrase inhibitors and can they be used in acute glaucoma?

Answer 4

Yes they can:

Acetazolamide, or topical dorzolamide

Question 5

What two hormones influence growth hormone release from somatotrophs? Is this promoted in hypoglycemia or hyperglycema?

Answer 5

1. GHRH
2. GHIH - somatostatin

Promoted in hypoglycemia since it functions to increase lipolysis / gluconeogenesis (builds lean muscle from fat)

Question 6

Where is IGF-1 produced and what is it under control of? What is its receptor type?

Answer 6

The liver, under control of GH receptor - JAK/STAT

This mediates most of the downstream effects of GH

Question 7

What syndrome is characterized by GH receptor mutation? How is it treated?

Answer 7

Laron-type dwarfism

Treated with IGF-1 replacement therapy, since that receptor is okay

Question 8

What is the current treatment of choice for growth hormone deficiency? Why is it long-acting?

Answer 8

Somatotropin - it has a short halflife, but IGF-1 has a much longer half life

Question 9

What are the approved indications for growth hormone treatment?

Answer 9

1. Pituitary dwarfism
2. Genetic disorders of Noonan syndrome, Prader-Willi (paternally imprinted 15q11) and Turner syndrome
3. Idiopathic short stature
4. Adult GH deficiency - due to pituitary adenoma / head trauma
5. Muscle wasting in AIDs

Question 10

What are the unapproved uses of GH?

Answer 10

1. Sports abuse

2. Anti-aging -> really doesn’t work in animal models

Question 11

What is recombinant IGF-1 called? When is it used?

Answer 11

Mecasermin

1. Laron syndrome
2. When anti-GH antibodies are present
3. Growth failures unresponsive to GH

Question 12

What are the manifestations of acromegaly?

Answer 12

GH excess in adult hood (vs gigantism in childhood)

Causes:

1. Generalized thickening of extremities with swelling of internal organs
2. Expansion of skull at fontanelle
3. Jaw protrusion
4. Life threatening complications: Enlarged heart, HBP, T2DM, heart / kidney failure

Question 13

What are the somatostatin analogs used to treat excess GH? What are their side effects?

Answer 13

Octreotide
Lanreotide

Side effects include nausea, gallstones, and flatulence (+ steatorrhea)

Question 14

What is the GH antagonist and when is it used?

Answer 14

Pegylated drug called “pegvisomant” - think of ants on the tire swing

Used if somatostatin agonists are ineffective at treating acromegaly

Question 15

What is the role of ADH in limiting blood loss during injury?

Answer 15

1. Induces secretion of Factor 8 and von Willebrand factor from vascular endothelium -> promotes clotting
2. Vasoconstriction

Question 16

What are three signals for ADH secretion?

Answer 16

1. Hyperosmolality
2. Volume depletion
3. Angiotensin II

-> inhibited by alcohol

Question 17

What are the ADH receptor subtypes?

Answer 17

V1 = vasoconstriction, Gq
Most important effects at physiological levels:
V2 = AQP2 channels to the membrane via cAMP, Gs

V2-like: factor 8 / von Willebrand

Question 18

What are the two types of diabetes insipidus and what causes them?

Answer 18

1. Central / Pituitary DI - deficiency in ADH production

2. Nephrogenic DI - unresponsiveness to ADH, most often due to lithium or demeclocycline (tetracycline drug)

Question 19

How is DI diagnosed?

Answer 19

Inability to concentrate urine after period of a fluid deprivation.

Then pituitary vs nephrogenic based on response to ADH

Question 20

What is the primary agent used to treat central DI, and its advantages over ADH?

Answer 20

Desmopressin - synthetic ADH agonist

• > less affinity for V1 receptors, diminishing vasoconstriction
• > more resistant to degradation, only need twice daily

Question 21

What can desmopressin be used for, other than central DI?

Answer 21

Nocturnal enuresis, and some coagulation disorders including von Willebrand disease and mild hemophilia A (factor 8 deficiency)

Question 22

What are the adverse reactions of desmopressin?

Answer 22

1. Vasoconstriction -> contraindicated in coronary artery disease
2. Water intoxification - really bad in high blood pressure and heart failure
3. Hyponatremia - due to overdilution of blood, manifests as headache and nausea before CNS effects. Avoid in renal failure

Question 23

What is syndrome of inappropriate ADH secretion (SIADH) and what does it cause?

Answer 23

Excess ADH secretion causing dilutional hyponatremia

Question 24

What can cause SIADH?

Answer 24

Multitudinous causes, most affecting CNS or ectopic lung production: brain tumor, trauma, meningitis / encephalitis, or small cell carcinoma of lungs

Question 25

What are the treatments for SIADH?

Answer 25

1. Water restriction
2. Loop diuretics
3. IV hypertonic saline
4. Demeclocycline - interferes with ADH