17: Pharmacology of Hypothalamic-Pituitary Axis

Somatropin

Somatotropin

Growth hormone

• Recombinant form of human GH (subQ/IM)

USE

• Confirmed GH deficiency in children & adults

• Children with genetic diseases associated with short stature 

  • Ex: Turner, Prader-Willi, Noonan, etc.

• Efficacy in treatment of AIDS-associated wasting & GH deficiency

AE

• Edema & hyperglycemia

  • Body tries to correct increased glucose in blood = edema 

• Pseudotumor cerebri

• Slipped capital femoral epiphysis

• Scoliosis 

NOTES

• Commonly abused due to ability to improve metabolism & lean body mass

  • Leads to acromegaly symptoms (bone overgrowth, sleep apnea, HTN, diabetes)

Somapacitan

USE 

• Treat adults with GH deficiency

• Once per week injection

AE

• Back/joint pain, weight gain, anemia, swelling in arms/legs, hypertension, increase in blood creatinine phosphokinase

Somatostatin

(Inhibits everything)

SS analogs (same function):

• Octreotide

• Lanreotide

MOA

• Physiologically inhibits GH secretion

USE

• Somatotroph adenomas (acromegaly)

AE 

• Significant GI disturbances, gallstones, cardiac conduction abnormalities

Mecasermin

• Recombinant human IGF-1

USE 

• Patients with GH insensitivity (Laron dwarfism) → may be deficient in IGF-1

AE

• Hypoglycemia (must administer within 20 mins of snack or meal)

  • Because IGF-1 stimulates body to use glucose released by GH

Bromocriptine

Dopamine D2 receptor agonist

MOA

• Block prolactin release

• At higher doses → can also slightly suppress GH in small GH-secreting tumors

USE

• Acromegaly (from GH deficiency), hyperprolactinemia

AE

• Psychosis, hallucinations

• Nausea, hypotension, dizziness

Pegvisomant

MOA 

• Antagonist → binds tightly to GH R

  • Blocks GH receptors by preventing them from dimerizing → no signaling

USE

• Acromegaly (stops GH from working)

Cabergoline

Dopamine D2 receptor agonist

MOA

• Dopamine D2 agonist → decreases prolactin release

  • Effective in reducing serum prolactin concentrations & restoring fertility 

USE

• Hyperprolactinemia (more effective + longer-acting than bromocriptine)

  • Usually causes infertility + disturbed menstruation in females & decreased libido + erectile dysfunction in males

AE

• Nausea, hypotension, dizziness

Desmopressin

Synthetic ADH

USE

• Diabetes insipidus

  • Problem where there is too little ADH action → pee out tons of dilute urine & get super thirsty

  • Promotes water reabsorption without increasing blood pressure

• Nocturnal enuresis (bed wetting), von Willebrand disease (clotting disorder) 

NOTES

• Does NOT cause vasoconstriction → little effect on blood pressure

Oxytocin

Controlled by +feedback

MOA 

• Positive feedback hormone (suckling + cervical stretch → more oxytocin)

• Loop stops when the action is done (birth, orgasm, ejaculation)

USE

• Induces labor, controls postpartum bleeding

NOTES

• Bonding hormone (especially in females → maternal bonding)

Vasopressin (ADH)

MOA 

• Conserves water in the DCT + collecting duct

• Causes vasoconstriction

USE

• Cardiogenic shock

AE 

• Hyponatremia, angina, MI