Posterior Pituitary Hormones

Chapter 36 Posterior Pituitary Hormones

Endocrine Functions of the Pituitary Anterior pituitary hormones: adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH).

Posterior pituitary hormones: oxytocin, vasopressin (antidiuretic hormone)

Posterior Pituitary Hormones Posterior pituitary: – Stores and releases 2 hormones that are produced in the hypothalamus: • Oxytocin: – Stimulates contractions of the uterus during parturition. – Stimulates contractions of the mammary gland alveoli.

• Vasopressin (Antidiuretic hormone, ADH): – Promotes the retention of water by the kidneys.

Oxytocin Oxytocin is a short polypeptide hormone released by the posterior pituitary that elicits milk ejection in lactating women and contributes to the initiation of labor.

【 Pharmacokinetics 】 Oxytocin is usually administered intravenously for stimulation of labor. It is also available as a nasal spray to induce lactation postpartum. It is inactive if swallowed, because it is destroyed in the stomach and intestine. Oxytocin is not bound to plasma proteins and is catabolized by the kidneys and liver, with a circulating half-life of 5 minutes.

【 Pharmacologic effects 】 Oxytocin alters transmembrane ionic currents in myometrial smooth muscle cells to produce sustained uterine contraction. The sensitivity of the uterus to oxytocin is increased during pregnancy. Oxytocin-induced myometrial contractions can be inhibited by β-adrenoceptor agonists, magnesium sulfate, or inhalation anesthetics. Oxytocin also causes contraction of myoepithelial cells surrounding mammary alveoli, which leads to milk ejection. Without oxytocin-induced contraction, normal lactation cannot occur. Oxytocin has weak antidiuretic and pressor activity.

【 Therapeutic uses 】 Oxytocin is used to induce labor and augment dysfunctional labor for (1) conditions requiring early vaginal delivery (eg, maternal diabetes, or preeclampsia); (2) uterine inertia; (3) incomplete abortion. Oxytocin can also be used for control of postpartum uterine hemorrhage. Impaired milk ejection may respond to nasal oxytocin.

【 Dosage 】 For induction of labor, oxytocin should be administered intravenously via an infusion pump with appropriate fetal and maternal monitoring. An initial infusion rate of 1 mU/min is gradually increased to 5-20 mU/min until a physiologic contraction pattern is established. For postpartum uterine bleeding, 10-40 units is added to 1 L of 5% dextrose, and the infusion rate is titrated to control uterine atony. Alternatively, 10 units can be given intramuscularly after delivery of the placenta. To induce milk let-down, one puff is sprayed into each nostril in the sitting position 2-3 minutes before nursing.

【 Adverse reactions & contraindications 】 When oxytocin is used properly, serious toxicity is rare. Among the reported adverse reactions are maternal deaths due to hypertensive episodes, uterine rupture, water intoxication, and fetal deaths. Afibrinogenemia has also been reported. Contraindications include fetal distress, prematurity, abnormal fetal presentation, cephalopelvic disproportion, and other predispositions for uterine rupture.

Vasopressin (Antidiuretic hormone, ADH) Vasopressin is a peptide hormone released by the posterior pituitary that possesses antidiuretic and vasopressor properties. A deficiency of this hormone results in diabetes insipidus.

【 Pharmacokinetics 】 Vasopressin is administered by intravenous, intramuscular, or intranasal routes; oral absorption is slight, quickly inactivated by trypsin. The half-life of circulating ADH is approximately 20 minutes, with renal and hepatic catabolism via reduction of the disulfide bond and peptide cleavage. A small amount of vasopressin is excreted as such in the urine.

【 Pharmacologic effects 】 Vasopressin interacts with two types of receptors. V1 receptors are found on vascular smooth muscle cells, liver and other tissues, and mediate vasoconstriction. V2 receptors are found on renal tubule cells and mediate antidiuresis through increased water permeability and water resorption in the collecting tubules. Thus the major use of vasopressin is to treat diabetes insipidus. Desmopressin acetate (DDAVP, 1-desamino-8-D-arginine vasopressin) is a long-acting synthetic analog of vasopressin with minimal V1 activity and an antidiuretic-to-pressor ratio 4000 times that of vasopressin.

【 Therapeutic uses 】 Vasopressin and desmopressin are the alternative treatments of choice for pituitary diabetes insipidus. Bedtime desmopressin therapy ameliorates nocturnal enuresis by decreasing nocturnal urine production. Vasopressin infusion is effective in some cases of esophageal variceal bleeding and colonic diverticular bleeding.

【 Dosage 1.】 Aqueous vasopressin Synthetic aqueous vasopressin is a short-acting preparation. The dose is 5-10 units subcutaneously or intramuscularly every 3-6 hours for transient diabetes insipidus and 0.1-0.5 units/min intravenously for gastrointestinal bleeding.

2. Desmopressin acetate This is the preferred treatment for most patients with central diabetes insipidus. Desmopressin may be administered intranasally, intravenously, subcautaneously, or orally. The typical nasal dosage is 10-40μg (0.1-0.4mL) daily in one to three divided doses. Nasal desmopressin is available as a unit dose spray that delivers 0.1 mL per spray. The dosage by injection of desmopressin is 1-4μg (0.25-1mL) daily every 1224 hours as needed for polyuria, polydipsia, or hypernatremia. For nocturnal enuresis, desmopressin, 10-20μg (0.1-0.2mL) intranasally at bedtime, is used.

【 Adverse reactions & contraindications 】 Overdosage can result in water intoxication and hyponatremic convulsions. Headache, nausea, abdominal cramps, agitation, and allergic reactions occur rarely. Vasopressin (but not desmopressin) can cause vasoconstriction and should be used cautiously in patients with coronary artery disease. Nasal insufflation of desmopressin may be less effective when nasal congestion is present.