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Endocrine Pharmacology

By; Seyoum Gizachew (B.Pharm., MSc.)

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Introduction

• The metabolic effects of the different systems of the body: – controlled by autonomic nervous system and the

secretions of the endocrine, or ductless glands. • Hormones: – heterogeneous group of chemicals, – released into the blood stream and travel to all parts of the

body. • The pharmacology of the individual hormones is of

importance, – under or over production of the hormones can have

striking metabolic consequences.

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Introduction cont…

• The hypothalamus and pituitary gland function cooperatively as master regulators of the endocrine system. – control reproduction, growth, lactation, thyroid and

adrenal gland physiology, and water homeostasis.• Deficiency or overproduction of these hormones disrupts

this control. • Clinical use of protein hormones in the past was limited; – Preparations had to come from glands or urine.

• Recombinant DNA techniques and the development of more stable analogues that can be injected in a depot form – permit increased and more effective use of these

hormones.

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Table: Hypothalamic Releasing and Inhibiting Hormones that regulate the anterior pituitary

Table: Pituitary Hormones

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Uterine Stimulants/ Oxytocics

1. Oxytocin• Is a cyclic 9–amino acid peptide• Synthesized in the paraventricular nucleus of the

hypothalamus• Transported to the posterior pituitary for storage. • Its mechanism of action–direct stimulation of oxytocin receptors found

on the myometrial cells. • Contract uterine smooth muscle.

• Also causes contraction of myoepithelial cells surrounding mammary alveoli,–leads to milk ejection.

• Circulates unbound in the plasma.• half-life of approximately 5-15 minutes. • primarily inactivated in the kidneys and

liver.

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Oxytocin cont…

• Generally considered to be the drug of choice for inducing labor at term.

• Successful in inducing and augmenting labor.– In patients with labor disorders.

• Used following incomplete abortion (retention of parts of the products of conception).

• may be used after full-term delivery to prevent or control uterine hemorrhage.

• Oxytocin in high doses is used to induce abortion. • Inappropriate use of oxytocin can lead to; – uterine rupture, – possibly maternal death.

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Oxytocin cont…

• Prolonged stimulation of uterine

contractions can result in the following fetal

adverse reactions:

–persistent uteroplacental insufficiency,

–sinus bradycardia, premature ventricular

contractions, other arrhythmias, and

–fetal death.

Dosing;

• Induction of labor,

– initial infusion rate of 0.5–2 mU/min is increased

every 30–60 min (max. infusion rate is 20 mU/min).

• Postpartum uterine bleeding,

– 10–40 units are added to 1 L of 5% dextrose, titrate

infusion rate to control uterine atony.

– Alternatively, 10 units of oxytocin can be

administered by IM after delivery of the placenta.

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2. Ergometrine

• Ergot (Claviceps purpurea) is a fungus that grows on rye.–contains a surprising variety of

pharmacologically active substances (Ergot alkaloids).

• In 1935, ergometrine,–isolated and was recognised as the

oxytocic principle in ergot.

Pharmacological actions: • Ergometrine contracts the human uterus. • Ergometrine also has a moderate degree

of vasoconstrictor action per se.–reduce bleeding from the placental bed

(the raw surface from which the placenta has detached).

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Ergometrine cont…

• Can be given orally, IM or IV. • Has a very rapid onset of action and its effect lasts for 3-6

hours. • Unwanted effects: – Vasoconstriction with an increase in blood pressure

associated with nausea, blurred vision and headache can occur,

– vasospasm of the coronary arteries resulting in angina.

Dosing: • Prevention and treatment of postpartum haemorrhage, – IM injection: 200 mcg immediately after birth.

• Excessive uterine bleeding: Slow IV injection: 250-500 mcg immediately after birth.