Pharmacology of the Hypothalamus and Pituitary Gland Flashcards
List the drugs that act on the hypothalamus
Octreotide, bromocriptine, cabergoline
List the drugs that act on the anterior pituitary
Somatropin, mecasermin, pegvisomant
List the drugs that act on the posterior pituitary
Oxytocin, Vasopressin, Desmopressin, Conivaptan
Which drug(s) are somatostatin analogs?
Octreotide
Which drug(s) are Dopamine (D2) agonists?
Bromocriptine, cabergoline
Which drug(s) are recombinant GH?
Somatropin
Which drug(s) are insulin-like growth factor 1?
Mecasermin
Which drug(s) are GH antagonists?
Pegvisomant
Which drug(s) are Antidiuretic hormone and analogs?
Vasopressin, desmopressin
Which drug(s) are vasopressin antagonists?
Conivaptan
What family of receptors do GH receptors belong to?
JAK/STAT cytokine receptors
Describe the regulation of release of growth hormone
- GHRH binds to its receptor on pituitary somatotrophs -> increase in intracellular cAMP and Ca2+
- GHRH acts synergistically with Ghrelin to promote GH release
- Ghrelin acts on a receptor that is distinct from the GHRH receptor
What is Mecasermin?
A recombinant form of IGF-1
Describe the interaction of IGF-1 and insulin receptors
Insulin receptors can activate IGF-1 receptors and vice versa
What is the therapeutic use of mecasermin?
In children with GH insensitivity syndromes d/t:
- GH receptor mutation (Laron syndrome)
- Mutation in the post-GH signaling pathway
What are the AE’s of Mecasermin?
Hypoglycemia (up to 40%) [must have a snack 20 min prior to dose]
What are the adverse effects of growth hormone in children?
- Scoliosis
- Increased ICP
- Headache
- Hyperglycemia
- Otitis media (in children with Turner syndrome)
What are the adverse effects of GH in adults?
- Peripheral edema (81%)
- Headache (18%)
- Arthalgias (23%)
- Myalgias (10%)
- Paresthesias (13%)
- Hypoesthesia (11%)
- Hyperglycemia
- Nerve numbness, muscle or joint pain; carpal tunner syndrome
What are the contraindications/precautions of GH?
- Diabetic retinopathy
- Pediatric patients w/ epiphyseal closure
- Acute clinical illness, neoplastic disease
Why is human somatostation not used?
It has limited therapeutic usefullness because of its short duration of action and its multiple effects in many secretory systems
What is octrotide?
A somatostatin analog
What is the MOA of somatostatin and its drugs?
Activation of somatostatin receptors decreases the synthesis of cAMP, which in turn leads to inhibition of GH secretion
What are the side effects of somatostatin?
GI effects, multi organ effects. It inhibits virtually all exocrine and endocrine secretions of the
- pancreas
- stomach
- intestine
- parathyroid
What is the therapeutic use of somatostatin?
It is used in patients suffering from gigantism and acromegaly.
(note: excessive GH secretion is almost always due to a pituitary adenoma)
What drugs can be used to combat gigantism and acromegaly and what are their classes/MOA?
- Octreotide - a somatostating analog
- Cabergoline, a D2 dopamine antagonist
- Pegvisomant, a GH receptor antagonist
(reminder: Gh receptors are JAK-STAT receptors)
what are the actions of prolactin?
- Stimulation of breast growth and milk production
- Inhibition of ovulation
What are the effects of hyperprolactinemia?
- Gynecomastia, low libido, ED, infertility in men
- Amenorrhea, galactorrhea in women (pre-menopausal)
What are the half-lives of bromocriptine and cabergoline?
Bromocriptine ~ 10hrs
Cabergoline ~65hrs
What are the AEs of dopamine agonists?
- Nausea, anorexia, vomiting, constipation
- Postural hypotension, cardiac arrhythmias
- Dyskinesias
- Headache, insomnia, nightmares, confusion
- Delusions, hallucination
What are the contraindications/precautions of D2 agonists?
- Psychotic disorders
- Hypertension
- History of fibrotic disorders
What are the therapeutic uses of D2 agonists?
- very effective at lowering prolactin levels
- tumor shrinkage (but will rebound upon discontinuation of drug)
- Hyperprolactinemia
- Cabergoline - acromegaly in combation with a somatostatin analog
What is the physiologic role of Oxytocin?
- Uterine muscle contraction
- Elicits milk ejection from the breast
What is the MOA of oxytocin?
- acts through GPCR and IP3 second messenger system to contract uterine smooth muscle
- Also stimulates release of PGs and LTs
What is the therapeutic use of oxytocin?
- induction and maintenance of labor
- stimulate milk ejection (nasal oxytocin)
- sometimes to control post-partum hemorrhage (however, ergot alkaloids are better)
What are the AEs of oxytocin?
- Hypertensive crisis
- Fetal distress, placental abruption, uterine rupture
- Fluid retention/water intoxication, hyponatremia, heart failure, seizures, death; fetal death
What is vasopressin?
Vasopressin is an anti-diuretic hormone (literally ADH)
What are the vasopressin receptors and what do they target?
- V1 - vasoconstriction increased inositide turn over and increased intracellular Ca2+
- V2 - increase cAMP (increase water permeability (via aquaporins) and resorption (via aquaporins) in the collecting tubules
What is desmopressin?
An ADH analog that specifically targets V2 receptors to increase anti-diuretic effect while limiting the vasoconstriction effect. It also has a longer half-life.
What are conivaptan and tolvaptan?
They are ADH antagonists.
