HPH- Khan

Explain GH signaling by JAK-STAT Pathway. Which other hormone uses this pathway?

GH binds to JAK-STAT receptor extracellularly. Then the intracellular domain phosphorylates multiple times. After phosphorylation, the STAT molecule dimerizes and activates transcription.

Prolactin also uses this pathway.

GH has structural resemblance to which other hormone?

Prolactin

What is JAK? What is STAT?

JAK- Janus Kinase, the enzyme that phosphorylates

STAT- signal transducer and activator of transcription

What is the Role of IGF?

• anabolic and growth promoting effects

  • increase bone growth, mineral density, muscle mass, and differentiation of fat cells

  • decreases BG

What are the adverse effects of Recombinant Growth Hormone?

• CANCER (neoplasms)

• DECREASE INSULIN SENSITIVITY

• others: peripheral edema, myalgia, arthralgia, carpal tunnel

What are the long-term complications of acromegaly?

CVD, respiratory disease, cancer

What 3 classes of agents can be used to treat acromegaly?

1. somatostatin analogues

2. dopamine agonists

3. GH receptor antagonists

What is the MOA of Somatostatin Analogs?

inhibit GH release from the pituitary gland

What is the MOA of Dopamine Agonists?

inhibits GH paradoxically by activating D2 receptor to inhibit prolactin release

What is the MOA of Pegvisomant?

GH receptor antagonist… AKA won’t let GH bind to target cells

What are the ADRs of Pegvisomant?

(i don’t think this is very important)

elevated LFTs, lipohypertrophy at injection site

What are the ADRs of Dopamine Agonists?

n/v, HA, postural hypotension

What is the role of dopamine in prolactin secretion?

dopamine is the molecule responsible for inhibiting the release of prolactin secretion

What are the causes of hyperprolactinemia?

• ANTIPSYCHOTIC DRUGs- D2 receptor antagonists

• tumors (pituitary, HT)

How would you treat hyperprolactinemia?

Dopamine agonists

What are the CNS adverse effects of Bromocriptine?

hallucinations, mood swings, psychosis, nightmare, insomnia

How does the half-life of cabergoline compare to bromocriptine?

cabergoline has longer half-live

Why is cabergoline preferred over bromocriptine?

greater efficacy, longer half life, less ADRs

Oxytocin and vasopressin are made up of a _______ amino acid peptide.

9 amino acid peptide

What causes the release of vasopressin?

• low bp

• high plasma osmolarity

Where are the V1a receptors located? What is their function?

• located- vascular smooth muscle

• function- vasoconstriction

Where are the V2 receptors located? What is their function?

• located- kidneys

• function- water reabsorption

True or False: V1a and V2 receptors use Tyrosine Kinase receptors.

FALSE—> use GCPRs

What are the indications for vasopressin use?

• DIABETES INSIPIDUS

• nocturnal enuresis

What is desmopressin?

long-acting analogue of vasopressin (ADH) with minimal V1a activity

What is an ADR of desmopressin?

hyponatremic convulsions

How is vasopressin different from desmopressin?

desmopressin does NOT cause vasoconstriction like vasopressin

What are the names of the 2 vasopressin antagonists?

• conivaptan

• tolvaptan

What are the MOA of each vasopressin antagonist?

conivaptan- V1a and V2 receptor antagonist

tolvaptan- V2 receptor antagonist

What is the major ADR of vasopressin antagonists?

osmotic demyelination syndrome

WHAT IS THE BOXED WARNING OF VASOPRESSIN ANTAGONISTS?

FATAL LIVER INJURY