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Posterior pituitary drugs
Posterior pituitary hormones are synthesized in the hypothala-mus and stored in the posterior pituitary, which, in turn, secretes the hormones into the blood. These drugs include:
§ all forms of antidiuretic hormone (ADH), such as desmopressin acetate and vasopressin
§ the oxytocic drug oxytocin
Because enzymes in the GI tract can destroy all protein hormones, these drugs can’t be given orally. Posterior pituitary drugs may be given by injection or intranasal spray.
Like other natural hormones, oxytocic drugs are usually absorbed, distributed, and metabolized rapidly. Parenterally administered oxytocin is absorbed rapidly; however, when it’s administered in-tranasally, absorption is erratic.
Under neural control, posterior pituitary hormones affect:
§ smooth-muscle contraction in the uterus, bladder, and GI tract
§ fluid balance through kidney reabsorption of water
§ blood pressure through stimulation of the arterial wall muscles.
ADH increases cyclic adenosine monophosphate (cAMP), which increases the permeability of the tubular epithelium in the kid-neys, promoting reabsorption of water. High dosages of ADH stim-ulate contraction of blood vessels, increasing the blood pressure.
Desmopressin reduces diuresis and promotes clotting by in-creasing the plasma level of factor VIII (antihemophilic factor).
In pregnant women, oxytocin may stimulate uterine contractions by increasing the permeability of uterine cell membranes to sodi-um ions. It also can stimulate lactation through its effect on mam-mary glands.
ADH is prescribed for hormone replacement therapy in patients with neurogenic diabetes insipidus (an excessive loss of urine caused by a brain lesion or injury that interferes with ADH synthe-sis or release). However, it doesn’t effectively treat nephrogenic diabetes insipidus (caused by renal tubular resistance to ADH).
Desmopressin is the drug of choice for chronic ADH deficiency and is administered intranasally. It’s also indicated for primary nocturnal enuresis. Desmopressin has a long duration of action and relatively few adverse effects.
Short-term ADH treatment is indicated for patients with tran-sient diabetes insipidus after head injury or surgery; therapy may be lifelong for patients with idiopathic hormone deficiencies.
Used for short-term therapy, vasopressin elevates blood pressure in patients with hypotension caused by lack of vascular tone. It also relieves postoperative gaseous distention.
Oxytocics are used to:
· induce labor and complete incomplete abortions
· treat preeclampsia, eclampsia, and premature rupture of mem-branes
· control bleeding and uterine relaxation after delivery
· hasten uterine shrinking after delivery
· stimulate lactation.
A variety of drugs can cause interactions with posterior pituitary drugs:
§ Alcohol, demeclocycline, epinephrine, and lithium may de-crease the ADH activity of desmopressin and vasopressin.
§ Chlorpropamide, clofibrate, carbamazepine, and cyclophos-phamide increase ADH activity.
§ Synergistic effects may occur when barbiturates or cyclo-propane anesthetics are used concurrently with ADH, leading to coronary insufficiency or arrhythmias.
§ Cyclophosphamide may increase the effect of oxytocin.
§ Concurrent use of vasopressors (anesthetics, ephedrine, methoxamine) and oxytocin increases the risk of hypertensive cri-sis and postpartum rupture of cerebral blood vessels. (See Ad-verse reactions to posterior pituitary drugs.)
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