Oxytocin & ADH/Vasopressin Pharmacology

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Posterior Pituitary Gland

Oxytocin

Oxytocin (Brand Name: Pitocin)

Oxytocin promotes myometrial uterine contractions to expel the fetus and promotes milk ejection. Recall that prolactin is necessary for milk production and secretion; oxytocin is required for its ejection.
Produces uterine contractions: it is used to induce labor in cases where it's medically necessary (preeclampsia, maternal diabetes, etc.). When the oxytocin receptors are stimulated, uterine contractions are induced or strengthened, helping to expel uterine contents.
Stops postpartum hemorrhage (the loss of 500 mL or more blood).

When the myometrium contracts, spiral arteries constrict and blood flow is reduced.

Side Effects

Beware of excessive dosage or hypersensitivity to oxytocin, which can lead to fetal distress or placental or uterine damage.

anti-diuretic hormone (ADH) (Vasopressin)

ADH actions on Kidney

In the kidney, ADH acts on the nephron collecting ducts to promote water reabsorption, thus increasing body water (and, therefore, blood volume, blood pressure, and cardiac output).
Vasoconstriction is a secondary function of ADH, which binds to vascular smooth muscle receptors (hence its alternative name, vasopressin); in hypovolemic shock, increased endogenous production of ADH is an important compensatory mechanism.

ADH Agonists

Central diabetes insipidus (ADH deficiency)

ADH agonists treat central diabetes insipidus, which is ADH deficiency and results in elevated serum sodium levels.
We show a collecting duct in which water runs out without being reabsorbed via vasopressin receptors.
There are high urine volumes with low osmolality.
Central diabetes insipidus is often a consequence of head trauma; there's a loss of ADH production and release from the hypothalamus.
Note that nephrogenic diabetes insipidus has the same end-outcome, hypernatremia due to water loss, but it is secondary to a lack of response to ADH within the kidney, an important distinction because it means that supplementing with ADH won't solve the problem.

ADH Antagonists

SIADH (syndrome of inappropriate ADH secretion)

ADH antagonists treat SIADH (syndrome of inappropriate ADH secretion), ADH excess which results in low serum sodium levels.
We show a collecting duct in which there is excess water reabsorption.
There are low urine volumes with high urine osmolality.

ADH receptor agonists: desmopressin and vasopressin

ADH receptor agonists, such as desmopressin and vasopressin, are used to treat central diabetes insipidus.
They increase the number of aquaporins and decrease water excretion. Desmopressin has selective action at V2 receptors whereas vasopressin acts at all receptors (V1, V2, V3).
As a result they reduce urine volume and increase urine osmolality.
These drugs are also used to treat nocturnal polyuria (frequent urination during the night) and nocturnal enuresis (bedwetting), both of which can have serious impact on a patient's quality of life.
From a hematological perspective, they are also used to treat hemophilia A and Von Willebrand clotting disorders because they increase Factor VIII and Von Willebrand factor (review the clotting process and disorders at the link in our notes).
They can be administered via injection, IV infusion, orally, or in a nasal spray.

Side Effect: Hyponatremia

As we can imagine, a major potential side effect is hyponatremia, due to excessive water retention (urine reduction), so we need to watch patients for sudden drops in sodium levels, which can cause seizures.
Patients may also experience GI problems, headaches, and flushing.

ADH receptor antagonists: Conivaptan and Tolvaptan

ADH receptor antagonists, such as Conivaptan and Tolvaptan, are used to treat SIADH,
Conivaptan blocks ADH V1a and V2 receptors, which increases water excretion in the kidneys. Tolvaptan is far more selective for V2 receptors, with minimal action on V1a receptors.
As a result, they increase urine volume and reduce urine osmolality.

Side Effect: Hypernatremia

A major potential side effect is hypernatremia.
Overly rapid correction of hyponatremia can lead to central pontine myelinolysis (aka osmotic demyelination syndrome) with white matter injury to pontine and extra-pontine (outside of the pons) central nervous system structures.

An unfortunate consequence of this syndrome can be locked-in syndrome, which we discuss in detail elsewhere.