Pharmacology of Hypothalamic Pituitary Axis

Somatropin: recombinant form of human GH (Subcutaneous/ IM)

• Used for confirmed GH deficiency in children and adults and in the treatment of children with genetic diseases
associated with short stature (e.g. Turner, Prader-Willi, Noonan and other syndromes)

• Has efficacy in treatment of AIDS-associated wasting and GH deficiency  and GH deficiency.

Adverse effects of Somatropin

• pseudotumor cerebri
• slipped capital femoral epiphysis
• Scoliosis
• Edema, and Hyperglycemia
HUMAN RECOMBINANT GROWTH HORMONE (HGH)• Increased risk of diabetes and hypertension if abused

Somapacitan

Used in adult patients with GH Deficiency. Once a week injection.

Adverse Effects: Back or joint pain, Weight gain, anemia, Swelling in arms or legs, Hypertension, Increase in blood creatinine phosphokinase

Mecasermin: recombinant human IGF-1

Used in patients with GH insensitivity (Laron dwarfism) may be deficient in IGF-1.
Adverse Effects: Hypoglycemia (must administer within 20 mins of snack or meal)

GROWTH HORMONE ANTAGONISTS

Somatostatin, Octreotide, bromocriptine, lanreotide, pegvisomant

GH excess usually results from a Somatotroph Adenoma and cause Acromegaly in adults and Gigantism in children and adolescents a Somatotroph Adenoma and cause Acromegaly in adults and Gigantism

Somatostatin Analogs

• MOA: Somatostatin physiologically inhibits GH secretion, making it a logical treatment for Somatotroph Adenomas. (Acromegaly)

• Octreotide (SandoSTATIN®), lanreotide (Somatuline®) = long-acting somatostatin analogs

Adverse effects of Somatostatin Analogs

cause significant gastrointestinal disturbances, gallstones, and cardiac conduction abnormalities.

Dopamine D2 Receptor Agonist: Bromocriptine

• MOA: Effective at inhibiting prolactin release (more than GH) but high doses have some efficacy in small GH secreting tumors. This effect may
be due, in part, to the shared embryonic lineage of lactotrophs and somatotrophs

Use: Acromegaly, Hyperprolactinemia

Pegvisomant 

• MOA: Pegvisomant works as an antagonist, binds tightly to the monomeric GH receptor, it prevents the receptor dimerization required or
subsequent receptor activation and intracellular signaling.

Use: Acromegaly.

Cabergoline and bramacriptine: dopamine receptor agonists 

effective in reducing serum
prolactin concentrations and restoring fertility.

• AE: nausea, hypotension, dizziness. With bromocriptine also psychosis, hallucinations.

Oxytocin

Oxytocin is used to stimulate uterine contractions in labor and to decrease bleeding in postpartum hemorrhage.

Plays an important role for bonding in females (esp. maternal bonding).

Positive feedback loop

Vasopressin (ADH) 

Vasopressin (aka Anti-Diuretic Hormone) ADH regulates blood pressure and volume by promoting water conservation in the Distal Convoluted Tubule and collecting duct and causing vasoconstriction.
Can be used for cardiogenic shock.

AE: hyponatremia, Angina, Myocardial Infarction.

Desmopressin

Desmopressin is synthetic ADH. Used for: diabetes insipidus, nocturnal enuresis (bed wetting) and von Willebrand disease (a genetic clotting disorder).

Desmopressin does not cause vasoconstriction! It has little effect on blood pressure.

AE: hyponatremia, headaches, dizziness