9.1 Hypothalamic-Pituitary Drugs
The hypothalamic-pituitary axis regulates multiple endocrine systems through releasing hormones and pituitary hormones. Pharmacological interventions target hormone deficiencies, excesses, and reproductive disorders.
Hypothalamic-Pituitary Axis
GnRH Analogs
Mechanism & Clinical Applications
GnRH Agonists: Continuous administration desensitizes GnRH receptors, paradoxically suppressing LH/FSH (after initial surge). Used for hormone-sensitive cancers and precocious puberty.
Agonists:
- • Leuprolide, goserelin: Prostate cancer, endometriosis, uterine fibroids
- • Initial flare (add antiandrogen for prostate cancer)
- • Adverse: Hot flashes, bone loss, impotence
GnRH Antagonists: Immediate suppression of LH/FSH without initial surge.
Antagonists:
- • Degarelix, elagolix: Prostate cancer, endometriosis
- • No tumor flare
- • Faster suppression than agonists
Growth Hormone (GH)
Somatropin (Recombinant GH)
Indications:
- • GH deficiency in children (↑ growth velocity)
- • Turner syndrome, Prader-Willi syndrome
- • Chronic kidney disease
- • AIDS-related wasting
Adverse Effects:
- • Hyperglycemia, insulin resistance
- • Peripheral edema
- • Arthralgias, carpal tunnel syndrome
- • Increased ICP (pseudotumor cerebri)
- • Slipped capital femoral epiphysis
GH Antagonists
Octreotide, Lanreotide
- • Somatostatin analogs (long-acting)
- • Use: Acromegaly, carcinoid tumors, VIPomas
- • ↓ GH, ↓ IGF-1, ↓ tumor hormone secretion
- • Adverse: GI upset, gallstones, glucose intolerance
Pegvisomant
- • GH receptor antagonist
- • Use: Acromegaly (refractory to somatostatin analogs)
- • Blocks GH effects (↓ IGF-1)
- • Adverse: Hepatotoxicity (monitor LFTs)
ADH (Vasopressin) & Analogs
Desmopressin (DDAVP)
Mechanism:
Selective V2 receptor agonist. Increases water reabsorption in collecting duct via aquaporin-2 insertion. Minimal V1 activity (no vasoconstriction).
Indications:
- • Central diabetes insipidus
- • Nocturnal enuresis (bedwetting)
- • Hemophilia A, von Willebrand disease (↑ vWF, factor VIII)
⚠️ Major Risk:
Hyponatremia: Water retention without electrolyte reabsorption. Monitor sodium levels, especially in elderly.
Restrict fluid intake to prevent water intoxication
ADH Antagonists (Vaptans)
Conivaptan, Tolvaptan
- • V2 receptor antagonists ("aquaretics")
- • Use: SIADH, hyponatremia (euvolemic/hypervolemic)
- • ↑ Free water excretion without electrolyte loss
- ⚠️ Correct Na+ slowly (avoid osmotic demyelination syndrome)
Clinical Notes
- • Do NOT use in hypovolemic hyponatremia (give NS)
- • Adverse: Hypernatremia, thirst, polyuria
- • Hepatotoxicity (tolvaptan); restrict duration
Oxytocin & Analogs
Clinical Applications in Obstetrics
Oxytocin:
- • Labor induction: Stimulates uterine contractions (↑ PGF2α, ↑ Ca²⁺)
- • Postpartum hemorrhage: Prevents/treats uterine atony
- • IV infusion (titrate to effect)
- • Also involved in milk letdown reflex
Adverse Effects:
- • Uterine hyperstimulation: Fetal distress, uterine rupture
- • Water intoxication (ADH-like effects at high doses)
- • Hypotension (rapid IV bolus)
Contraindications:
- • Cephalopelvic disproportion
- • Abnormal fetal position
- • Placenta previa/abruptio
Prolactin Modulators
Dopamine Agonists
Dopamine tonically inhibits prolactin release via D2 receptors. Agonists suppress prolactin, shrink prolactinomas.
- Bromocriptine:
- • Ergot derivative; D2 agonist
- • Hyperprolactinemia, prolactinomas
- • Adverse: Nausea, orthostatic hypotension, hallucinations
- Cabergoline:
- • Longer half-life, better tolerated
- • Weekly dosing
- • Preferred over bromocriptine
Clinical Scenarios
Hyperprolactinemia
- • Galactorrhea, amenorrhea, infertility
- • Hypogonadism (prolactin ↓ GnRH)
- • First-line: Dopamine agonists
Prolactinomas
- • Most common pituitary tumor
- • Medical therapy (cabergoline) shrinks tumors
- • Surgery if refractory or compressive symptoms