Enzaprost

Enzaprost is a drug that increases the contractility and tone of the myometrium. Contains elements of PG.

In obstetrics, only 3 of all PGs are used: PG-E1 (the substance alprostadil), PG-E2 (the component dinoprostone), and PG-F2α (the element dinoprost), because these PGs help to contract the muscles of the uterus and provoke the maturation of the cervix.

The PG-F2 element is a reduced variant of PG-E2 (in vivo tests, PG-F2 is formed by spontaneous transformation of the PG-E2 element).

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Indications Enzaprost

It is used as a means of terminating pregnancy in the 2nd trimester, under the following circumstances:

• spontaneous but incomplete abortion;
• death of the fetus in the womb;
• severe abnormalities in the development of the fetus or congenital disorders that are incompatible with life (diagnosed by ultrasound or other modern prenatal diagnostic procedures);
• if there is a need to postpone an artificial abortion to the 2nd trimester – due to the high probability of complications developing in a woman if the procedure is performed in the 1st trimester.

Release form

The drug is released in the form of an injection liquid - inside ampoules with a volume of 1 ml (5 pieces inside a pack).

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Pharmacodynamics

During pregnancy, the binding of PG elements inside the chorion with the amnion and placenta increases, which causes the PG level in the woman's blood and amniotic fluid to increase.

The principle of influence.

Dinoprost with dinoprostone stimulate the activity of phospholipase C, which facilitates the passage of calcium ions through the cell walls. As a result, the intracellular level of Ca increases, which causes the myometrium to contract. The above-mentioned PGs are also involved in the processes of "maturation" of the cervix. Smooth muscle cells have specific endings to PG-E2 and PG-F2α, interaction with which allows them to develop their effect on target cells.

At the same time, these PGs improve the transport of signals within the myometrium, leading to the formation of intercellular contacts, and also helping to form and increase the number of oxytocin endings within the uterus.

Other effects.

With local application of PG, there is a pronounced multifocal loosening of connective tissues, in which fibroblasts with activity appear (they cause fine-grained loosening in the cytoplasm, and also increase the size of mitochondria (by their vacuolization) and increase the number of vacuoles or increase the vesicular structure inside the cytoplasm of peripheral cellular sections). At the same time, the activity of collagenase and elastase doubles (approximately sevenfold), and in addition, a significant increase in hyaluronidase values is noted. All of these factors help to soften the cervix.

Collagenases are mainly formed from neutrophils, which, when PG is administered in large volumes, accumulate within the cervical stroma (this is also observed during full-term births).

The increase in the activity of natural killer cells (NK cells) that develops with the participation of PG also helps to stimulate labor and may be the cause of miscarriages that occur.

In this regard, the elements of PG, firstly, help soften the cervix and, secondly, provoke labor. Both of these effects are used during therapy.

Pharmacokinetics

Absorption.

Dinoprost is absorbed at a low rate through the amniotic fluid into the circulatory system. It takes 6-10 hours (with intra-amniotic administration of a single dose of 40 mg) to reach Cmax. The Cmax level is 3-7 ng/ml.

Exchange processes.

Enzymatic oxidation of dinoprost occurs mainly in the liver and lungs of the woman. The effect of 15-OH dehydrogenase converts dinoprost into an intermediate ketone, which is oxidized to the element 2,3-dinor-6-keto-PG-F1α.

Excretion.

The drug is mainly excreted through the kidneys, in the form of metabolic components. 5% of the drug is excreted with feces. The half-life of Enzaprost in amniotic fluid is 3-6 hours. Data obtained from testing showed that the plasma half-life of dinoprost after intravenous injection is less than 60 seconds.

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Dosing and administration

When terminating a pregnancy of less than 15 weeks, 0.25-1 g of the substance should be administered intra-amniotically with 1-2 hour intervals. When the pregnancy is over 15 weeks, a deep puncture of the amniotic sac is performed through the peritoneum. At least 1 ml of the amniotic fluid should be removed from the sac, and then 40 mg of the drug should be administered into it.

When performing the procedure, the initial 5 mg should be administered at a very low rate. If there is no abortion after 24 hours from the moment of using the drug, another 10-40 mg of the substance should be administered. If there is no effect, it is not advisable to administer the medication further (for more than 2 days).

To induce labor or eliminate uterine content in the 3rd trimester, a half-hour intravenous infusion of the drug is performed (at a concentration of 15 mcg/ml, at a rate of 2.5 mcg/minute). If the uterine muscles are moving at an adequate rate, the rate may be maintained. Under other conditions, the rate is increased by 2.5 mcg/minute every hour. The maximum permissible rate per minute is 20 mcg. If uterine hypertonicity develops, the infusion must be stopped. If there is no medicinal effect after 12-24 hours, the drug is discontinued.

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Use Enzaprost during pregnancy

Injectable Enzaprost is used as a means of terminating pregnancy. When performing such a procedure, all required actions must be taken to complete it, because the effect of the drug on the fetus has not been studied.

In animal testing, large doses of PG E and F resulted in increased bone tissue proliferation. A similar effect was also found in clinical situations – with prolonged use of PG-E1.

Short-term use of dinoprost does not lead to the above changes in the fetus.

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Contraindications

Main contraindications:

• history of allergy or other signs of intolerance to dinoprost or other uterotonic substances;
• history of or current asthma;
• obstructive pulmonary pathology in chronic form or an active stage of pulmonary disease;
• regional enteritis or ulcerative colitis of non-specific type;
• hyperthyroidism;
• glaucoma;
• infectious diseases in the active phase;
• acute forms of inflammation in the pelvic area or peritoneum (for example, chorioamnionitis, leading to strong uterine contractions that should not occur);
• destruction of the integrity of the amniotic membrane (due to which the likelihood of intravascular absorption of dinoprost increases);
• malpresentation of the fetus;
• significant discrepancy in the size of the fetal head and the woman's pelvis (clinical or anatomical);
• elevated blood pressure in pregnant women;
• sickle cell anemia.

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Side effects Enzaprost

Side effects include:

• changes in laboratory test data: sometimes the number of leukocytes increases;
• problems with the functioning of the cardiovascular system: sometimes a spasm in the peripheral vessels or anaphylaxis is observed. Tachycardia, pain or a feeling of tightness in the chest area, bradycardia, chest pain and a second-degree block may be observed;
• disorders of the nervous system: sometimes headaches, anxiety, paresthesia, drowsiness, diplopia and hyperhidrosis occur;
• damage to the visual organs: burning sensation in the eyes is occasionally observed;
• disorders associated with the functioning of the respiratory system, mediastinum and sternum: sometimes a prolonged cough appears. Rarely, bronchial spasms develop;
• manifestations in the gastrointestinal tract: occasionally severe prolonged pain or pain in the epigastric region, as well as intestinal obstruction of a paralytic nature, occur. Vomiting, stomach pain or colic, diarrhea and nausea develop occasionally;
• problems with the kidneys and urinary tract: sometimes there is urinary retention, hematuria or dysuria;
• lesions associated with the function of connective tissues and the musculoskeletal system: pain in the back, shins and shoulders occasionally appears;
• systemic and local disorders: sometimes there is intense thirst, hyperhidrosis or chills, transient fever, tremors and reddening of the epidermis. Pain and inflammation may occur in the injection area;
• disorders of the mammary glands and the reproductive system: sometimes the uterine tone increases or uterine pain develops during an abortion. Occasionally, swelling of the mammary glands is observed, associated with the influx of blood, as well as a burning sensation in this area.

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Overdose

Clinical symptoms of poisoning include vomiting, diarrhea and nausea, which are more intense than when standard doses are administered.

If necessary, specific treatment procedures are performed: surgery to open the amniotic sac. Supportive measures: replacement therapy through infusion.

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Interactions with other drugs

The use of Enzaprost in combination with ergometrine and oxytocin may potentiate its therapeutic effect and increase the incidence of negative symptoms.

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Storage conditions

Enzaprost should be stored in a place closed to small children. The temperature level is within the 15°C mark.

Shelf life

Enzaprost can be used for a period of 3 years from the date of manufacture of the pharmaceutical substance.

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Analogues

Analogues of the drug are Prepidil, Dinoprobioston with Mirolyut, as well as Misonewel, Prostin e2 and Misoprostol.

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