Anterior Pituitary Pharmacology PDF
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Uploaded by RegalElder7207
Washington Union High School
Manish Issar
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Summary
These notes provide an overview of anterior pituitary pharmacology, including hormone secretion, mechanisms of action of treatments for deficiencies and excesses, and potential side effects. It covers various hormones and their functions.
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Anterior Pituitary Pharmacology Manish Issar, Ph.D Department of Basic Medical Sciences, WUHS Office: HEC 1st Floor, Rm # 1210 Learning Objectives Identify and describe various hormones that are secreted by th...
Anterior Pituitary Pharmacology Manish Issar, Ph.D Department of Basic Medical Sciences, WUHS Office: HEC 1st Floor, Rm # 1210 Learning Objectives Identify and describe various hormones that are secreted by the anterior pituitary gland. Identify and describe mechanism of action of agents used to treat GH deficiency and overproduction in adults and children. Identify and describe the adverse effects of agents used to treat the deficiency and hypersecretion of GH and prolactin in adults and children Identify and describe the indications for use of GH, mecasermin/mecasermin rinfabate. Anterior Pituitary Hormones POMC Somatotropic Glycoprotein derived hormones hormones α- ACTH GH PRL LH FSH hCG MSH TSH HYPOTHALAMUS-PITUITARY AXIS Hypothalamic releasing hormones o Corticotropin-releasing hormone (CRH) o Growth hormone-releasing hormone (GHRH) (+) o Gonadotropin-releasing hormone (GnRH) o Thyrotropin-releasing hormone (TRH) ▪ Somatostatin (SST): (–) pituitary GH and TSH ▪ Dopamine (DA): (–) pituitary PRL Somatotropin-release inhibiting factor [SRIF]; PRL = prolactin TREATMENTS FOR GH DEFICIENCY GROWTH HORMONE Somatropin GROWTH HORMONE Somatotropins Growth hormone (GH) GH → dwarfism GH → acromegaly (gigantism of pituitary origin) Physiological actions of GH Impairs glucose uptake by tissues ↓ glucose utilization in peripheral tissues ↑ lipolysis ↑ muscle mass ↑ gluconeogenesis in hepatocytes ↓ insulin receptor sensitivity ↓ post receptor insulin action GH: MECHANISMS OF ACTION Growth Hormone Somatropin SOMATROPIN Indirect Effect Direct Effect liver IGF-1 (autocrine) IGF-1 Target Clonal expansion (endocrine) tissue (differentiation/proliferation) GROWTH HORMONE INDICATIONS FOR USE GH deficiency Tx pediatric patients with short stature Prader-Willi syndrome with growth failure Turner syndrome Idiopathic short stature Tx of wasting in pts. with AIDS Tx of pts. with short bowel syndrome. GROWTH HORMONE SIDE EFFECTS Pancreatitis, gynecomastia, carpal tunnel syndrome, CYP450 induction, peripheral edema, myalgias and arthalgias. Care with diabetic pts on insulin therapy. Hyperglycemia, edema, increased risk of asphyxiation in severely obese pt’s with Prader-Willi syndrome and airway obstruction. MECASERMIN / MECASERMIN RINFABATE INDICATION: Growth failure in children w/ Primary IGF-1 deficiency (IGFD) GH gene deletion w/ developed neutralizing antibodies to GH What is mecasermin? rhIGF-1 DAYliSe How does mecasermin differ from mecasermin rinfabate? ROUTE: Parenteral (s.c.) SIDE EFFECT: hypoglycemia, intracranial hypertension, adenotonsillar hypertrophy. TREATMENTS FOR GH EXCESS (ACROMEGALY) DOPAMINE AGONISTS: Bromocriptine Cabergoline short half-life longer half-life (~65 hr in healthy) high affinity for D2 receptors Not FDA approved for use in pregnancy COMMON SIDE EFFECTS: CNS : dizziness, headache, lightheadedness, fatigue GI : nausea and vomiting (DA D2 in area postrema), abdominal pain, diarrhea WARNING: Cabergoline, associated with valvular heart disease due to stimulation of serotonin 5-HT2B receptors TREATMENTS FOR GH EXCESS (ACROMEGALY) SOMATOSTATIN (SST) ANALOGS Octreotide : long acting parenteral (i.v./s.c.) Sandostatin : i.m. 1 x month. Long acting Lanreotide (Depot): i.m., 1 x month Pasireotide : i.m., 1 x month COMMON MECHANISM: agonists at the SST receptors SST-analog N Cell membrane α γ GDP β Adenylate cyclase C αi cAMP TREATMENTS FOR GH EXCESS (ACROMEGALY) SOMATOSTATIN (SST) ANALOGS SIDE EFFECTS: Most common: Diarrhea, nausea, abdominal cramps, malabsorption of fat and flatulence Cholelithiasis – inhibit CCK release and gallbladder motility, most pts. asymptomatic Octreotide/lanreotide: injection-site pain, conduction abnormalities, biliary tract disorders, subclinical hypothyroidism, abnormalities with glucose metabolism. Pasireotide: similar to octreotide/lanreotide EXCEPT for higher incidence of hyperglycemia (61-67% vs 25-30%). TREATMENTS FOR GH EXCESS (ACROMEGALY) GH RECEPTOR ANTAGONISTS PEGVISOMANT – given s.c. MECHANISM: GH Positive Cellular response GH PEGV GH No Cellular response TREATMENTS FOR GH EXCESS (ACROMEGALY) GH RECEPTOR ANTAGONISTS PEGVISOMANT Cont.. SIDE EFFECTS: Injection site pain GI complaints (nausea and diarrhea) Significant elevations in hepatic aminotransferase (25%) Flu-like symptoms Tumor growth (small fraction of pts.) peptide broken hormone down gat TREATMENTS FOR HYPERPROLACTIN SECRETION HYPERPROLACTINEMIA Most common causes: Prolactinomas DA receptor antagonists (antipsychotics, oral contraceptives) DA blockade in Tuberoinfundibular pathway PROLACTIN TREATMENTS FOR HYPERPROLACTIN SECRETION HYPERPROLACTINEMIA Most common drugs used: Bromocriptine Cabergoline MECHANISM: Agonist at DA receptor (Tuberoinfundibular pathway) PROLACTIN Both drugs are Category B for pregnancy