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Hypothalamic & Pituitary Hormones. Kaukab Azim, MBBS, PhD. Uses of Hypothalamic & Pituitary Hormones. Short stature due to hypopituitarism (Pituitary dwarfism) Acromegaly and gigantism Carcinoid syndrome, VIPoma , and ruptured esophageal varices Hyperprolactinemia

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Kaukab Azim, MBBS, PhD

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Hypothalamic

&

Pituitary Hormones

Kaukab Azim, MBBS, PhD


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

  • SIADH


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


Growth hormone releasing hormone(GHRH)

GHRH analog:Sermorelin

Used 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

IGF-1 as Peripheral effector


Molecular and Cellular Basis of GH Action


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.

Growth hormone (Somatotropin)

Gluconeogenesis


Short stature due to Congenital/acquired GH deficiency (Pituitary Dwarfism)

GH deficiency in adults

Turner’s syndrome

AIDS related muscle wasting

Therapeutic uses of GH


In children

Increased Intracranial tension

Headache

Papilledema

Scoliosis

Diabetes mellitus

In adults

Peripheral edema

Arthritis

Arthralgia

Myalgia

Carpal tunnel syndrome

Diabetes mellitus

GH preparations:Adverse effects


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


Acromegaly

To prevent gigantism

Carcinoid syndrome

VIPoma, gastrinoma

Ruptured esophageal

varices

Somatostatin analogs: Therapeutic uses


Somatostatin analogs: Adverse drug reactions

  • GIT problems: abdominal cramps, diarrhea, malabsorption, steatorrhea

  • Gall stones

  • Vitamin B12 deficiency

  • Cardiovascular problems: Sinus bradycardia, conduction disturbances


GH antagonist

Pegvisomant

  • Decreases IGF-1; GH remains high

  • Also effective in those who do not/stop responding to octreotide


Prolactin

Secretion of prolactin is under the control of dopamine (prolactin inhibiting hormone)secreted by hypothalamus


Prolactin


Hyperprolactinemia

  • Prolactin secreting pituitary adenoma

  • Drug induced hyperprolactinemia

    • Antipsychotics

    • Metochlopramide

      Drugs to manage hyperprolactinemia:

    • Bromocriptine

    • Cabergoline (ka-BER-goe-leen)


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


Oxytocin : Adverse reactions

  • Cardiac arrhythmia, CNS stimulation, excessive uterine contractions, and hyponatremia.

  • Contraindications:

    • Fetal distress

    • Abnormal fetal presentation

    • Prematurity

    • CPD (cephalo-pelvic disproportion)


Vasopressin (arginine-vasopressin)

Vasopressin has:

  • Antidiuretic activity

  • Vasopressor activity (Vasoconstriction)

  • Decreased secretion/response to ADH causes Diabetes insipidus

  • Excessive secretion of ADH causes: SIADH


  • Vasopressin receptors

    • V1 receptors:

      • On vascular smooth muscles

      • Pressor effect: meditated through IP3/DAG ↑Ca+2

    • V2 receptors

      • Renal:On distal and collecting duct cells of nephron

        • Antidiuretic effect: mediated through↑cAMP

      • Extrarenal:

        • Release of coagulation factorsVIIIc and Von willebrand factor


    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


  • SIADH

    • Due to excessive secretion of ADH

      Drug induced SIADH:

      • Carbamazepine, vinca alkaloids, Chlorpropamide

        Drugs to manage SIADH

      • Demeclocycline

      • Conivaptan (vasopressin antagonist)


    Questions…


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