Mechanism of Action on the Myometrium and Cervix
Dinoprostone belongs to a group of agents that primarily stimulate rhythmic uterine contractions. Unlike oxytocin preparations, which exhibit a strict dependence on the gestational age, prostaglandins have a universal effect. Myometrial sensitivity to dinoprostone is maintained at all stages of pregnancy, making it the drug of choice for both labor induction and pregnancy termination.
Furthermore, the drug addresses a crucial clinical task of the first stage of labor: synchronizing contractility with the dilation of the birth canal. In cases of delayed cervical dilation (rigidity, dystocia), dinoprostone promotes cervical "ripening" by relaxing the tissues and accelerating effacement and dilation.
Systemic Effects and Metabolism
Prostaglandin preparations exert systemic effects on the body. A comparison with dinoprost ($PGF_{2\alpha}$) highlights several key features of dinoprostone:
- Respiratory and Cardiovascular Systems: The drug dilates the bronchial lumen and pulmonary blood vessels, and exhibits a hypotensive effect (lowers blood pressure).
- Gastrointestinal Tract: Similar to dinoprost, the drug actively stimulates the motility of intestinal smooth muscle.
- Renal Effects and Electrolytes: $PGE_2$ inhibits sodium reabsorption in the renal tubules, enhancing the diuretic effect. Loop diuretics (furosemide, ethacrynic acid) exert part of their initial hemodynamic action (pulmonary vasodilation) precisely through the stimulation of COX-2 expression and increased synthesis of prostaglandin E2. Prolonged use of dinoprostone itself can induce hypomagnesemia. Notably, the drug's efficacy does not depend on blood acid-base balance fluctuations.
Clinical Application and Pharmacokinetics
In clinical practice, dinoprostone is used for two main obstetric purposes:
- Labor Induction. The drug is administered orally, via intravenous infusion, or intravaginally (as a special gel).
- Medical Abortion. Intravenous infusion is commonly used for pregnancy termination.
A key pharmacokinetic feature of dinoprostone is its rapid inactivation. Metabolism occurs in the pulmonary vasculature as well as in the kidneys, spleen, intestines, and adipose tissue. The rate of destruction is so high that the half-life is only 90 seconds (during which time 97% of the intravenously administered active substance disappears from plasma).
Specific Adverse Effects
The high biological activity of prostaglandins accounts for a wide spectrum of potential adverse reactions:
- Gastrointestinal Disturbances: Due to increased smooth muscle motility, patients frequently report nausea, vomiting, and diarrhea.
- Thermoregulation Disorders: Dinoprostone can stimulate the thermoregulatory center in the hypothalamus, clinically manifesting as fever and chills.
- Vascular and Neurological Reactions: Severe headaches and marked hypotension may occur, requiring close monitoring of the patient's condition during therapy.