Pituitary Pharmacology - Self Study Flashcards Preview

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Flashcards in Pituitary Pharmacology - Self Study Deck (25):

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

Epinephrine - no


What are the ophthalmic beta blockers?

timolol, carteolol, betaxolol


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

Brimonidine, apraclonidine


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

Yes they can:
Acetazolamide, or topical dorzolamide


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

2. GHIH - somatostatin

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


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

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

This mediates most of the downstream effects of GH


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

Laron-type dwarfism

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


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

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


What are the approved indications for growth hormone treatment?

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


What are the unapproved uses of GH?

1. Sports abuse
2. Anti-aging -> really doesn't work in animal models


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

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


What are the manifestations of acromegaly?

GH excess in adult hood (vs gigantism in childhood)

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


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


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


What is the GH antagonist and when is it used?

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

Used if somatostatin agonists are ineffective at treating acromegaly


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

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


What are three signals for ADH secretion?

1. Hyperosmolality
2. Volume depletion
3. Angiotensin II

-> inhibited by alcohol


What are the ADH receptor subtypes?

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

V2-like: factor 8 / von Willebrand


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

1. Central / Pituitary DI - deficiency in ADH production
2. Nephrogenic DI - unresponsiveness to ADH, most often due to lithium or demeclocycline (tetracycline drug)


How is DI diagnosed?

Inability to concentrate urine after period of a fluid deprivation.

Then pituitary vs nephrogenic based on response to ADH


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

Desmopressin - synthetic ADH agonist

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


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

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


What are the adverse reactions of desmopressin?

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


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

Excess ADH secretion causing dilutional hyponatremia


What can cause SIADH?

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


What are the treatments for SIADH?

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