Hypothalamic and Pituitary Hormones Flashcards
Drugs that mimic or block the effects of hypothalamic and
pituitary hormones have pharmacologic applications in
three main areas:
(1) as replacement therapy for hormone
deficiency states
(2) as antagonists for diseases that result from
excess production of hormones
(3) as diagnostic tools for identifying endocrine
abnormalitie
Growth Hormone overview? Pharmacodynamics?
- Predominantly required during childhood & adolescence
- Effects mediated mainly by IGF-1
Pharmacodynamics
• Mediates effects via cell surface receptors that activate JAK/STAT signaling cascades
Physiological effects of GH(somatotropin)?
• Stimulation of longitudinal growth of bones
• Increased bone mineral density
• Increased muscle mass (in GH deficient people)
• Increased GFR
• Stimulation of preadipocyte differentiation into adipocytes
• Anti-insulin actions (decreased glucose utilization &
increased lipolysis)
• Development & increased function of immune system
Growth Hormone(somatotropin ) clinical pharmacology?
Clinical Pharmacology
Growth Hormone Deficiency
• Genetic or damage to pituitary or hypothalamus
• Short stature and adiposity (in children)
• Hypoglycemia (unopposed insulin action)
Criteria for Diagnosis
(1) A growth rate < 4cm per year, and
(2) the absence of a serum GH response to two GH
secretagogues
recombinant GH PK and analogs?
Somatropin = recombinant GH Somatrem = GH analog
Pharmacokinetics
• Active blood levels = persist for ~ 36 h
• Given subcutaneously 3-7 times a week
Growth failure in pediatric patient with primary therapeutic goal of growth, list etiologies
Growth hormone deficiency Chronic renal failure Noonan syndrome Prader-Willi syndrome Short stature homeoboxcontaining gene deficiency Turner syndrome Small for gestational age with failure to catch up by age 2 Idiopathic short stature in pediatric patients
Clinical use of recombinant GH in
Growth hormone deficiency in adults:
Wasting in HIV +ve patients:
Short bowel syndrome in
patients who are receiving
specialized nutritional support:
Growth hormone deficiency in adults: Improved metabolic state,
increased lean body mass,
sense of well-being
Wasting in HIV +ve patients: Increased lean body mass, weight, and physical endurance
Short bowel syndrome in
patients who are receiving
specialized nutritional support: Improved GI function
Recombinant GH AE in children?
- Generally well tolerated
- Scoliosis (during rapid growth)
- Hypothyroidism
- Intracranial hypertension (rare)
- Otitis media (increased risk for Turner Syndrome patients)
- Pancreatitis, gynecomastia & nevus growth
- Diabetic syndrome (chronic use)
Recombinant GH AE for adults and contraindications?
Adults • Peripheral edema, myalgias & arthralgias (hands & wrists especially) • Carpal tunnel syndrome • Proliferative retinopathy (rare) Contraindications • Cytochrome P450 inducer • Patients with a known malignancy
IF1-Analog and use?
• Small number of children with growth failure have IGF-1
deficiency
• Causes: mutations in gene that encodes for GH receptor
& development of neutralizing antibodies to GH
Mecasermin
• Complex of recombinant human IGF-1 and recombinant
human IGF-binding protein-3
Mescasermin AE?
- Hypoglycemia (eat 20 min before or after admin.)
- Intracranial hypertension (rare)
- Asymptomatic elevation of liver enzymes (rare)
GH secreting tumor symptoms?
• GH-producing cells (somatotrophs) can form secreting
tumors (more commonly in adults)
Symptoms
• Acromegaly (abnormal growth of cartilage, bone tissue,
skin, muscle, heart, liver & GI tract)
• Giantism (if occurs before long bone epiphyses close)
GH secreting tumor treatments?
• Small GH-secreting adenomas can be treated with GH
antagonists:
• GH receptor antagonists;
• somatostatin analogs; or
• dopamine receptor agonists
• Larger pituitary adenomas require surgery or radiation
Analog example of somatostatin and what does it inhibit?
Octreotide
• Somatostatin inhibits release of GH, TSH glucagon, insulin
& gastrin
Somatostatin analog octreotide PK?
Pharmacokinetics
• 45 x more potent in inhibiting GH release than
somatostatin
• 2 x more potent in reducing insulin secretion
• t ½ = ~ 80 min (30 x somatostatin)
• Octreotide acetate long-acting suspension can be given
at 4 week intervals
Somatostatin analog octreotide clinical applications?
Clinical Applications
• Reduces symptoms caused by hormone-secreting
tumors: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, nesidioblastosis, watery diarrhea, hypokalemia, achlorhydria syndrome & diabetic diarrhea.
• Localizing neuroendocrine tumors
• Acute control of bleeding from esophageal varices
Somatostatin analog octreotide AE?
Adverse Effects
• Nausea, vomiting, abdominal cramps, flatulence,
steatorrhea (with bulky bowel movements)
• Constipation
• Biliary sludge & gallstones (20-30% patients after 6 month
use)
• Sinus bradycardia (25%) & conduction disturbances(10%)
• Vitamin B12 deficiency (may occur with long-term use)
• Pain at injection site = common (esp. with long-acting)
Two examples of dopamine agonists?
Bromocriptine and Cabergoline
Pharmacokinetics
• Oral or as vaginal inserts
• Bromocriptine t1/2 = ~7 h
• Cabergoline t1/2 = ~65 h
Clinical applications of dopamine agonists?
Clinical Applications
• Hyperprolactinemia
Standard treatment. Dopamine agonists shrink pituitary
prolactin-secreting tumors, lower circulating prolactin
levels, and restore ovulation in ~70% women with
microadenomas & ~30% with macroadenomas
• Acromegaly
Alone or in addition to surgery, radiation or octreotide
admin
Dopamine agonists AE?
Adverse Effects
• Nausea (bromocriptine>cabergoline), headache, lightheadedness,
orthostatic hypotension, fatigue
• Psychiatric manifestations occasionally occur
• High doses = cold-induced peripheral digital vasospasm
• Chronic high-dosage therapy = pulmonary infiltrates
