Enzaprost

Enzaprost is a medicine that increases the contractility and tone of the myometrium. It contains elements of PG.

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

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

[1]

Indications Enzaprosta

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

• spontaneous, but not completed abortion;
• fetal death within the womb;
• severe abnormalities in the development of the fetus or congenital disorders that are incompatible with life (diagnosed during ultrasound or other modern prenatal diagnostic procedures);
• when the need to transfer artificial abortion on the 2nd trimester is due to the high probability of complications in a woman if the procedure is performed in the 1st trimester.

Release form

The release of the medication is realized in the form of an injection liquid - inside ampoules having a volume of 1 ml (5 pieces inside a pack).

[2], [3]

Pharmacodynamics

During pregnancy, the binding of the PG elements inside the chorion with the amnion and the placenta increases, due to which the GH index inside the blood and amniotic fluid of the woman increases.

The principle of influence.

Dinoprost with dinoprostone stimulates the activity of phospholipase C, which allows calcium ions to ease the passage through the cell walls. As a result, the intracellular level of Ca increases, causing myometrium to contract. These GHGs are also participants in uterine cervix ripening processes. Smooth muscle cells have specific endings for PG-E2 and PG-F2α, the interaction with which allows them to develop their effects on target cells.

At the same time, GHG data improves the transport of signals within the myometrium, leading to the formation of intercellular contacts, as well as helping to form and increase the number of oxytocin terminations inside the uterus.

Other effects.

With local use of PG, there is a pronounced multi-focal loosening of connective tissues, in which fibroblasts possessing activity arise (they cause fine-grained loosening in the cytoplasm area, 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 cells) ). At the same time, the activity of collagenase and elastase is doubled (it is approximately all possible), and in addition there is a significant increase in the values of hyaluronidase. All of these factors help soften the uterine neck.

Collagenases are mainly formed from neutrophils, with the introduction of PGs, large volumes of cumulative cells inside the cervical stroma (this is also observed during births occurring in time).

The increase in activity of natural killer cells (NK-cells), which develops with the participation of PGs, also helps to stimulate childbirth and may cause miscarriages that occur.

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

Pharmacokinetics

Absorption.

Dinoprost is absorbed at low speed through the amniotic fluid inside the circulatory system. To obtain Cmax values, it requires within 6-10 hours (with intra-amnial use of a single dose of 40 mg). The Cmax level is 3-7 ng / ml.

Exchange processes.

The enzyme oxidation of dinoprost is mainly realized inside the liver, as well as the lung of a woman. The effect exerted by 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. With faeces, 5% of drugs are excreted. The term half-life of Enzaprosta from an amniotic fluid is 3-6 hours. The information obtained during testing showed that the term of the plasma half-life of dinoprost with intravenous injection is less than 60 seconds.

[4]

Dosing and administration

In the event of an abortion, whose duration is less than 15 weeks, it is necessary to inject 0.25–1 g of the substance intra-amnually with 1-2-hour breaks. For periods of more than 15 weeks, a deep puncture of the membranes of the fetus is performed through the peritoneum. From the bladder you need to remove at least 1 ml of the existing amniotic fluid, and then inject 40 mg of the drug into it.

During the procedure, the initial 5 mg should be administered at a very low speed. In the absence of abortion a day after the use of the drug, you need to enter more within 10-40 mg of the substance. If the effect is absent, to drive the medication further (over 2 days) is impractical.

For induction of labor or elimination of uterine content, a half-hour intravenous drug infusion is performed in the 3rd trimester (at a concentration of 15 µg / ml, with a speed equal to 2.5 µg / minute). With an adequate pace of the muscles of the uterus speed is allowed to maintain. Under other conditions, the speed is increased every hour by 2.5 µg / minute. The maximum allowed speed per minute is 20 micrograms. With the development of uterine hypertonus requires the cessation of infusion. In the absence of medical influence after 12-24 hours, the medication is canceled.

[10], [11]

Use Enzaprosta during pregnancy

Injection Enzaprost is used as a means of terminating a pregnancy. When carrying out such a procedure, it is necessary to take all the required actions in order to complete it, because the effect of drugs on the fetus has not been investigated.

When testing with animals, large portions of PG E, as well as F, resulted in increased bone tissue proliferation. In clinical situations, a similar effect was also revealed - with prolonged use of PG-E1.

A short application of dinoprost does not lead to the above changes in the fetus.

[5]

Contraindications

The main contraindications:

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

[6], [7]

Side effects Enzaprosta

Among the side effects:

• changes in laboratory data: sometimes the number of leukocytes increases;
• problems with the work of the cardiovascular system: sometimes there is a spasm in the region of peripheral vessels or anaphylaxis. There may be tachycardia, pain or a feeling of tightness in the chest zone, bradycardia, pain in the chest and a 2nd degree blockade;
• Disorders of NA: sometimes there are headaches, anxiety, paresthesia, drowsiness, diplopia and hyperhidrosis;
• lesions of the visual organs: occasionally there is ocular burning sensation;
• disorders associated with the work of the respiratory system, mediastinum and sternum: sometimes there is a long cough. Occasionally develop bronchial spasms;
• manifestations in the gastrointestinal tract: occasionally there is severe prolonged pain or pain in the epigastric zone, as well as intestinal obstruction, which has a paralytic nature. Vomiting, stomach pain or colic, diarrhea, and nausea develop sporadically;
• problems in the work of the kidneys and urethra: sometimes there is urinary retention, hematuria or dysuria;
• lesions associated with the function of connective tissue and ODA: occasionally pain in the back, legs and shoulders;
• systemic and local disorders: sometimes there is severe thirst, hyperhidrosis or chills, transient fever, trembling and redness of the epidermis. In the area of the injection may occur pain and inflammation;
• disorders of the breast and reproductive system: sometimes uterine tone increases or uterine pain develops during abortion. There is rarely a swelling of the mammary glands associated with blood flow, as well as a burning sensation in this area.

[8], [9]

Overdose

Among the clinical symptoms of poisoning are vomiting, diarrhea and nausea, which have a higher intensity than in the case of the introduction of standard servings.

If required, specific treatment procedures are performed: an operation to open the amniotic bladder. Supporting actions: conducting substitution treatment through infusion.

[12], [13]

Interactions with other drugs

Using Enzaprost in combination with ergometrine and oxytocin can potentiate its therapeutic effects and increase the number of developing negative symptoms.

[14], [15], [16], [17]

Storage conditions

Enzaprost needs to be kept in a closed place from small children. The temperature level is within 15 ° С.

Shelf life

Enzaprost can be used for a 3-year period from the moment the pharmaceutical substance is manufactured.

[18]

Analogs

Analogues of drugs are Prepidil, Dinoprobioston with Mirolyut, as well as Mizonewell, Prostin e2 and Misoprostol.

[19], [20]