Post on 02-Jan-2016
description
Kaukab Azim, MBBS, PhD
Hypothalamic &
Pituitary Hormones
Uses of Hypothalamic & Pituitary Hormones
➲ Short stature due to hypopituitarism (Pituitary dwarfism)
➲ Acromegaly and gigantism
➲ Carcinoid syndrome, VIPoma, and ruptured esophageal varices
➲ Hyperprolactinemia
➲ Induction of labor
➲ Diabetes insipidus
➲ SIADH2
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Concepts in Endocrinology➲ Primary, secondary and tertiary endocrine disorders
➲ Feedback regulation
➲ Endocrine disorders: Deficiency, or Excess
➲ Mechanisms of action
➲ Uses of hormones /analogs: Diagnostic use Therapeutic use
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Growth hormone releasing hormone(GHRH)
GHRH analog: SermorelinUsed rarely as a diagnostic test for GH responsiveness
Growth Hormone
➲ Secretion of GH is stimulated by GHRH and inhibited by GIH (somatostatin)
➲ GH preparations for therapeutic use: Somatropin: Recombinant
human GH Somatrem: Recombinant human
GH
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IGF-1 as Peripheral
effector
Molecular and Cellular Basis of GH Action
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Growth hormone (Somatotropin)➲ Most of the actions of GH are
mediated by IGF-1 (somatomedins) - the peptides produced in the liver and cartilage.
➲ The somatomedins stimulate skeletal growth, amino acid transport, protein synthesis, nucleic acid synthesis and cell proliferation.
Gluconeogenesis
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Therapeutic uses of GH
➲ Short stature due to Congenital/acquired GH deficiency (Pituitary Dwarfism)
➲GH deficiency in adults
➲ Turner’s syndrome➲AIDS related muscle
wasting
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GH preparations: Adverse effects
In children➲ Increased Intracranial tension➲ Headache➲ Papilledema➲ Scoliosis➲ Diabetes mellitus
In adults➲ Peripheral edema➲ Arthritis➲ Arthralgia➲ Myalgia➲ Carpal tunnel syndrome➲ Diabetes mellitus
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Growth hormone inhibiting hormone(Somatostatin)
Somatostatin analogs:
➲ Octreotide – S/C, daily➲ Sandostatin-LAR - (Slow release preparation of octreotide) once every 4 weeks
➲ Administration of somatostatin analogs result in decrease in GH and IGF-1 levels
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Somatostatin analogs: Therapeutic uses
➲ Acromegaly
➲ To prevent gigantism
➲ Carcinoid syndrome
➲ VIPoma, gastrinoma
➲ Ruptured esophageal
varices
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Somatostatin analogs: Adverse drug reactions
➲ GIT problems: abdominal cramps, diarrhea, malabsorption, steatorrhea
➲ Gall stones ➲ Vitamin B12 deficiency➲ Cardiovascular problems: Sinus bradycardia,
conduction disturbances
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GH antagonist
Pegvisomant
➲ Decreases IGF-1; GH remains high➲ Also effective in those who do not/stop
responding to octreotide
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Prolactin
Secretion of prolactin is under the control of dopamine (prolactin inhibiting
hormone) secreted by hypothalamus
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Prolactin
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Hyperprolactinemia
➲ Prolactin secreting pituitary adenoma
➲ Drug induced hyperprolactinemia➲ Antipsychotics
➲ Metochlopramide
Drugs to manage hyperprolactinemia:
➲ Bromocriptine
➲ Cabergoline (ka-BER-goe-leen)
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Oxytocin
Actions meditated through
IP3/DAG ↑ Ca+2
Therapeutic uses
➲ To induce and augment labor after cervix has ripened
➲ To control post-partum hemorrhage
➲ To improve milk ejection – nasal oxytocin
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Oxytocin : Adverse reactions
➲ Cardiac arrhythmia, CNS stimulation, excessive uterine contractions, and hyponatremia.
➲ Contraindications:
Fetal distress Abnormal fetal presentation Prematurity CPD (cephalo-pelvic disproportion)
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Vasopressin (arginine-vasopressin)
Vasopressin has:
Antidiuretic activity Vasopressor activity (Vasoconstriction)
➲ Decreased secretion/response to ADH causes Diabetes insipidus
➲ Excessive secretion of ADH causes: SIADH
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Vasopressin receptors
1. V1 receptors:
➲ On vascular smooth muscles➲ Pressor effect: meditated through IP3/DAG ↑Ca+2
2. V2 receptors
➲ Renal: On distal and collecting duct cells of nephron Antidiuretic effect: mediated through ↑cAMP
➲ Extrarenal: Release of coagulation factors VIIIc and Von
willebrand factor
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Therapeutic uses of vasopressin/analogs
➲Vasopressin (Pitressin)
Therapeutic uses• Advanced Cardiac life support• Bleeding esophageal varices
➲Desmopressin Long-acting synthetic analog of vasopressin Antidiuretic : vasopressor activity = 3000:1
Therapeutic uses:• Neurogenic diabetes insipidus• Von Willebrand disease and hemophillia• Enuresis
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SIADH
• Due to excessive secretion of ADH
Drug induced SIADH:
Carbamazepine, vinca alkaloids, Chlorpropamide
Drugs to manage SIADH
Demeclocycline Conivaptan (vasopressin antagonist)
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Questions…