Posterior Pituitary Hormones

• Overview:  posterior pituitary hormones

  • Oxytocin

  • Vasopressin

    • Synthesis Site:

      • Hypothalamus:  posterior pituitary:  stored :  released

• Oxytocin:  Overview

  • Levels:

    • Physiologic levels result in milk ejection in lactating women.

    • Pharmacological doses:

      • Induce uterine contraction/maintain labor

  • Chemistry:  oxytocin

    • 9-amino acid peptide

  • Pharmacokinetics:  oxytocin

    • IV administration for labor stimulation

    • Nasal spray: postpartum lactation induction

    • Catabolism: renal and hepatic

    • Half-life: (circulating) 5 min.

  • Pharmacodynamics:  oxytocin

    • Influences ionic currents in myometrial smooth muscle :  uterine contraction

    • Uterine sensitivity to oxytocin: ­ increases in pregnancy

    • Inhibition of oxytocin-induced myometrial uterine contraction:

      •  Magnesium sulfate

      •  β-adrenergic receptor agonists

      •  Inhalation anesthetics

    • Promotes myoepithelial cell contraction (surrounding mammary alveolar) :   milk ejection

    • Normal lactation requires oxytocin

• Clinical Uses:  oxytocin

  • Diagnostic Applications:  oxytocin

    • Checking placental circulatory reserve:

      • IV oxytocin near-term results in uterine contractions with possible decrease fetal blood supply

        • Fetal heart rate response monitored with abnormal response possibly suggesting intrauterine growth retardation in consideration of  cesarean section.

  • Therapeutic Uses:  oxytocin

    • Labor induction

    • Promoting dysfunctional labor

      1. When early vaginal delivery is required

         • Rh factor concerns, maternal diabetes, preeclampsia

      2. Uterine inertia

      3. Incomplete abortion

    • Control of postpartum uterine bleeding

    • Enhance impaired milk ejection (nasal Route of Administration)

•  Toxicity:  oxytocin

  • Serious toxicity: rare

  • Reported adverse reactions include: hypertensive reactions, uterine rupture, water intoxication, fetal death, afibrinogenemia

•  Contraindications:  oxytocin

  • Fetal distress, abnormal fetal presentations, factors predisposing to uterine rupture

   

• Vasopressin:  Overview:

  • Peptide hormone

  • Released by posterior pituitary in reaction to:

    • Rising plasma tonicity

    • Decreasing blood pressure

  • Antidiuretic properties

  • Vasopressor properties

  • Vasopressin deficiency: :   diabetes insipidus

• Structure:  vasopressin

  • Nonapeptide

• Pharmacokinetics:  vasopressin

  • Routes of administration:

    • IV, intramuscular, intranasal

  • Half-life: 20 minutes

  • Renal and hepatic catabolism

  • Minimal vasopressin excreted unchanged in the urine

• Pharmacodynamics:  vasopressin

  • Receptor types:

    • V₁ mediates vascular smooth muscle (vasoconstriction)

    • V₂ receptors on renal tubule cells promote antidiuresis

      • Mechanism:

        • (1) increased water permeability and

        • (2) increased collecting tubule water resorption

    • Extrarenal V₂ receptors--promote coagulation factor VIII_c and von Willebrand factor release.

  • Desmopressin acetate (DDAVP, 1-desamino-8-D-arginine vasopressin)

    • Synthetic vasopressin derivative

    • Long-acting

    • Limited V₁ receptor activity

    • Significant antidiuretic/vasopressor ratio compared to vasopressin (4000: 1)

• Clinical Use:  vasopressin

  • Vasopressin and desmopressin: alternative treatment for pituitary diabetes insipidus

  • Nocturnal enuresis (desmopressin at bedtime) -- mechanism: reduced night urine production

  • IV vasopressin: may be effective in managing esophageal variceal bleeding and colonic diverticular leading

• Toxicity

  • Vasopressin (not desmopressin): vasoconstriction may cause issues in patients with coronary vascular disease

  • Unusual side effects include: agitation, allergic reactions, abdominal cramping, headache, nausea

   

Primary Reference: Fitzgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 603-618.

Primary Reference: Biller, Beverly M. K. and Daniels, Gilbert, H. Neuroendocrine Regulation and Diseases of the Anterior Pituitary and Hypothalamus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1972-1998