Gynipral
Synonyms: Hexoprenaline.
Pharmachologic effect. In connection with the influence on the 6a2-adrenergic receptors of the uterus, it has a tocolytic (relaxing the muscles of the uterus) effect. Corresponds to the drug hexoprenaline.
Indication for use. Used as a tocolytic agent in case of threat premature birth(in the third trimester of pregnancy), with acute intrauterine asphyxia of the fetus (impaired blood supply to the fetus), during childbirth (with discoordinated labor - improper contractions of the uterus during childbirth), to suppress uterine contractions before surgical intervention(incision of the cervix, cesarean section).
Method of administration and dosage. Ginipral is used intravenously and inside (in tablets). A "shock" dose (in acute cases) is injected intravenously slowly - 5-10 μg of ginipral in 10-20 ml of isotonic sodium chloride solution. For infusions (with long-term treatment), dilute 50 μg (contents of 2 ampoules of 25 μg each - "concentrate" of ginipral) in 500 ml of 5% glucose solution. Injected at a rate of 25 drops per minute (about 0.125 μg per minute). If necessary, the dose is increased by 5 drops every 5 minutes. The minimum injection rate is 10 drops per minute, maximum speed introduction - 60 drops per minute.
The tablets begin to be taken 2-3 hours before the end of the parenteral (intravenous) administration. First, 1 tablet is prescribed, then after 3 hours, 1 tablet every 4-6 hours; only 4-8 tablets per day.
Side effect. Headache, anxiety, tremors (tremors of the limbs), sweating, dizziness are possible. Rarely - nausea, vomiting. There are isolated reports of intestinal atony (loss of tone); an increase in the content of serum transaminases (enzymes). An increase in the mother's heart rate, a decrease in blood pressure, especially diastolic ("lower" blood pressure), is possible. In several cases, ventricular extrasystoles(cardiac arrhythmias) and complaints of pain in the region of the heart. These symptoms disappear after stopping treatment. The fetal heart rate in most cases does not change or changes little. An increase in the concentration of glucose (sugar) in the blood. This effect is more pronounced in patients with diabetes mellitus. Decreased urine output (urination), especially in initial phase treatment. During the first few days of treatment, a decrease in the concentration of calcium in the blood plasma is possible; in progress further treatment the calcium concentration is normalized.
Contraindications Thyrotoxicosis (disease thyroid gland); cardiovascular diseases, especially tachyarrhythmia (heart rhythm disturbance), myocarditis (inflammation of the muscles of the heart), lesions mitral valve, idiopathic hypertrophic subaortic stenosis (non-inflammatory disease of the muscle tissue of the left ventricle of the heart, characterized by a sharp narrowing of its cavity); serious illnesses kidney and liver; angle-closure glaucoma (increased intraocular pressure); heavy uterine bleeding; premature detachment of the placenta; infectious lesions endometrium (inner lining of the uterus); hypersensitivity to the drug, especially in patients with bronchial asthma.
Release form. In ampoules containing 0.025 mg or 0.01 mg each; tablets of 0.5 mg.
Storage conditions.
Isoxuprine (Isoxsuprine )
Synonyms: Duvadilan.
Pharmachologic effect. It has a tocolytic (relaxing the muscles of the uterus) effect by stimulating beta-adrenergic receptors. Reduces the tone of smooth muscles blood vessels skeletal muscles, eliminates spasm (sharp narrowing of the lumen) of blood vessels, increases blood supply to tissues
Indication for use. Threat of premature birth, obliterating endarteritis (inflammation of the inner lining of the arteries of the extremities with a decrease in their lumen), Raynaud's disease (narrowing of the lumen of the vessels of the extremities), spasm peripheral vessels.
Method of administration and dosage. With the threat of premature birth, intravenous drip infusion is prescribed (100 mg of the drug per 500 ml of 5% glucose solution) at a rate of 1-1.5 ml / min; the rate of administration is gradually increased to 2.5 ml / min. When the condition improves (cessation of contractions), they switch to intramuscular injection drug: within 24 hours - 10 mg every 3 hours. In the next 48 hours, 10 mg every 4-6 hours. After that, within 2 days, isoxsuprine is prescribed orally, 20 mg 4 times a day. In diseases of peripheral vessels, it is prescribed orally at 20 mg 4 times a day. In more severe cases, intravenous drip administration is prescribed (20 mg of the drug per 100 ml of 5% glucose solution) at a rate of 1.5 ml / min 2 times a day. Intramuscular administration of the drug, 10 mg 3-4 times a day, is also possible.
Side effect. Tachycardia (increased heart rate), hypotension (lower blood pressure), dizziness, flushing of the upper half of the body, to the face with parenteral administration(intravenously and intramuscularly); nausea, vomiting, rash.
Contraindications Recent bleeding, hypotension (low blood pressure), angina pectoris.
Release form. Tablets of 0.02 g of isoxsuprine hydrochloride in a package of 50 pieces; solution for injection (in 1 ml 5 mg of isoxsuprine hydrochloride) in 2 ml ampoules in a package of 6 pieces.
Storage conditions. List B. In a cool place.
PARTUSISTEN (Partusisten)
Synonyms: Fenoterol.
Pharmachologic effect. It has a tocolytic (relaxing the muscles of the uterus) effect. Belongs to the group of beta2-adrenostimulants. Corresponds to the drug fenoterol.
Indication for use. The experience of using partusisten shows that it is effective remedy to eliminate the threat of premature birth and does not adversely affect the fetus and newborn.
Method of administration and dosage. Assign intravenously (drip) and inside in the form of tablets. Soon after the start of intravenous administration, there is usually a significant decrease in pain, the tension of the uterus is relieved, then the pain and contractions of the uterus completely stop.
Inside take 5 mg every 2-3 hours; daily dose- up to 40 mg. At hypersensitivity(the appearance of tachycardia / increased heart rate /, muscle weakness, etc.) reduce a single dose to 2.5 mg, and the daily dose to 30 mg. The duration of the course of treatment is 1-3 weeks. Intravenous drip (0.5 mg in 250-500 ml of 5% glucose solution) is injected at 15-20 drops per minute until the contraction of the uterus is inhibited.
Partusisten is used in specialized medical institutions under close medical supervision.
Side effect. The drug can cause tachycardia, tremors (tremors) of the hands, muscle weakness, decreased blood pressure, sweating, nausea, and vomiting. It is noted that side effects are reduced under the influence of verapamil - 30 mg intravenously.
Contraindications Heart defects, cardiac arrhythmias, thyrotoxicosis (thyroid disease), glaucoma (increased intraocular pressure).
Release form. Ampoules of 0.025 mg; tablets of 0.5 mg.
Storage conditions. List B. In the dark place.
RITODRIN (Ritodrinum)
Synonyms: Prempar, Pre-Par, Utopar.
Pharmachologic effect. The action is close to fenoterol, salbupart and other beta2-adrenergic agonists.
Indication for use. It is used as a tocolytic (relaxing the muscles of the uterus) means with the threat of premature termination of pregnancy.
Method of administration and dosage. Inside appoint 5-10 mg 4-6 times a day. Usually, at these doses, uterine contractions stop and the possibility of maintaining pregnancy increases. The duration of the drug is 1-4 weeks. With the onset of preterm labor, oral (through the mouth) use is not effective enough and the drug is administered intravenously; To do this, dilute 50 mg of the drug in 500 ml of isotonic sodium chloride solution and inject it drip, starting at 10 drops per minute, then gradually increase the rate of administration (15 drops) until the uterus is completely relaxed. To continue the effect, the drug is administered intramuscularly at 10 mg every 4-6 hours, after which it is administered orally at 10 mg 4-6 times a day with a gradual dose reduction.
Ritodrin, as well as partusisten, is used in specialized medical institutions.
Side effects and contraindications. Possible side effects and precautions are the same as with Partusisten.
Release form. 5 mg tablets; ampoules of 10 mg.
Storage conditions. List B. In the dark place.
SALBUPART
Synonyms: Salbutamol, Ventolin, Ekovent, etc.
Pharmachologic effect. By its action on the contractile activity of the uterus, salbupart is close to partusisten. Refers to beta2-adrenostimulants. Corresponds to the drug salbutamol.
Indication for use. It is used as a tocolytic (relaxing the muscles of the uterus) means to eliminate the threat of premature birth, as well as after operations on the pregnant uterus.
Method of administration and dosage. Introduced intravenously. The contents of one ampoule (5 mg) are diluted in 400-500 ml of isotonic sodium chloride solution or 5% glucose solution. Enter at a rate of 15-20 drops (starting with 5 drops) per minute. The rate of administration depends on the intensity of uterine contractions and tolerance (monitor heart rate and other hemodynamic parameters). Duration of administration is 6-12 hours.
Side effects and contraindications are the same as for partusisten.
Release form. 0.1% solution in capsules of 5 ml (5 mg).
Storage conditions. List B. In the dark place.
TERBUTALIN (Terbutalin)
Synonyms: Brikanil, Arubendol, Betasmak, Brika-lin, Brikan, Brikar, Drakanil, Spiranil, Terbutol, Tergil, etc.
Pharmachologic effect. By pharmacological properties close to salbutamol. It has a tocolytic (relaxing the muscles of the uterus) effect.
Indication for use. Used as a tocolytic (relaxing the muscles of the uterus) means to eliminate the threat of premature birth.
Method of administration and dosage. As a tocolytic agent (in obstetric practice) is used in the form of drip intravenous infusions (10-25 μg per minute in isotonic glucose or sodium chloride solution) with a further transition to subcutaneous injections (250 μg = 1/2 ampoule) 4 times a day for 3 days. At the same time, 5 mg is administered orally 3 times a day.
Side effects and contraindications are the same as for partusisten (see page 378).
Release form. Tablets of 0.0025 g (2.5 mg) in a package of 20 pieces; 0.05% solution (0.5 mg) of terbutaline sulfate in ampoules containing 1 ml each, in a package of 10 ampoules.
Storage conditions. List B. In the dark place.
TROPACIN (Tropacinum)
Synonyms: Diphenyltropine hydrochloride, Tropazin.
Pharmachologic effect. In terms of pharmacological properties, tropacin is close to atropine (see page 92). In obstetric practice, it is used as an antispasmodic (relieving spasms) agent that inhibits the contractile activity of the uterus.
Indication for use. As a tocolytic (relaxing the muscles of the uterus) a remedy for the threat of premature birth and abortion.
Method of administration and dosage. As a tocolytic agent inside 0.02 g 2 times a day.
Side effects and contraindications
Release form. Tablets 0.001; 0; 003; 0.005; 0.01; 0.015 g in a package of 10 pieces.
Storage conditions. List A. In a well-closed container, protected from light.
Tocolytic drugs(Greek tokos childbirth + lysis relaxation) - drugs that weaken the contractile activity of the myometrium; used for threatening miscarriage and to prevent premature birth.
The most effective T. s. are drugs that stimulate b 2 -adrenergic receptors of the uterus (partusisten, ritodrin, salbutamol). They do not have high selectivity in relation to the myometrium and, simultaneously with relaxation of the uterine muscles, cause effects associated with the excitation of other β-adrenergic receptors (expansion of the bronchi, some tachycardia, suppression of intestinal motility, etc.).
Along with b-adrenomimetics, the contractility of the myometrium can be inhibited by drugs from other groups of pharmacologically active compounds. Thus, most drugs for anesthesia inhibit the contractile activity of the myometrium at the stage of deep anesthesia, only fluorothane causes relaxation of the muscles of the uterus during superficial anesthesia. Tocolytic properties are characteristic of ethyl alcohol. The activity of the myometrium decreases under the influence of progesterone and non-steroidal anti-inflammatory drugs. The tocolytic effect of the latter is associated with the inhibition of the activity of prostaglandin-N-synthetase and a decrease in this regard in the content of prostaglandins in the myometrium. Myotropic vasodilators (apressin, dihydralazine, diazoxide), along with relaxation of vascular smooth muscles, also cause relaxation of the myometrium. In addition, there is information about a decrease in contractile activity with parenteral administration of magnesium sulfate and blockers calcium channels... Wide application as T. c. these drugs were not received, because they are less effective than b-adrenergic agonists. At the same time, it is necessary to take into account the depressing effect of such drugs on the contractility of the myometrium when they are prescribed for other indications during pregnancy and childbirth.
Partusisten(Partusisten) by chemical structure is fenoterol hydrobromide (see. Adrenomimetics ). Along with the effect on the myometrium, it has a pronounced bronchodilator effect,
to a lesser extent relaxes the intestinal muscles. The effect of partusisten on the cardiovascular system is manifested by an increase in the mother's heart rate, an increase in cardiac output, a decrease in peripheral resistance and, as a result, a decrease in blood pressure (mainly diastolic). Partusisten can increase blood sugar due to glycogenolytic action, and also stimulates lipolysis, reduces serum potassium.The tocolytic effect with intravenous administration of partusisten appears after a few minutes and reaches a maximum after about 10 min... At the end of the administration, the effect of the drug stops depending on the dose after 5-80 min.When partusisten is administered orally, the effect occurs after 30 min and continues 3-4 h.
As side effects Partusisten can cause tachycardia, anxiety, nausea, vomiting, and weakening of intestinal motility in the mother. Partusisten is used for threatening miscarriage, to prevent premature birth,
as well as with labor complicated by excessive contractions during the period of disclosure and expulsion. Partusisten is prescribed by mouth at 0.005 G every 2-3 h... Daily dose - up to 0.04 G... When tachycardia and muscle weakness appear, reduce the single dose to 0.0025 G, and daily up to 0.03 G... The duration of the course of treatment is 1-3 weeks. Intravenous partusisten is injected drip at 0.0005 G at 250-500 ml 5% glucose solution at a rate of 15-20 drops in 1 min before the suppression of the contractile activity of the uterus. Contraindications to the appointment of partusisten are heart diseases, including heart defects and rhythm disturbances, intrauterine infection. Method of issue: in ampoules of 0.0005 G; tablets of 0.005 G.Rhythodrin(Ritodrinum; synonym for prempar, etc.) in structure and action is close to partusisten. It is used when there is a threat of premature termination of pregnancy. Assign inside at 0.005-0.01 G 4-6 times a day for 1-4 weeks. When preterm labor begins, the drug is administered intravenously,
Drugs that can affect the contractions of the uterus are called tocolytics (if they relax it) and tokomimetics (if they cause contractions).
Tocolytics
Tocolytics are used very often during pregnancy, almost all pregnant women manage to get acquainted with these drugs before the baby is born.
Tocolytics are substances that directly affect the muscles of the uterus, suppressing its contractions. The importance of these medications during pregnancy cannot be underestimated. Thanks to tocolytic patience, it is possible to remove and eliminate the threat of miscarriage, and it is thanks to them that you can fight hypoxia in the baby and delay his birth until the due date with such a complication as uterine hypertonicity and. Tocolytics are used all over the world, it is one of the most wonderful discoveries obstetrics.
Tocolytic therapy is carried out both on an outpatient basis and in a maternity hospital.
It turned out that many substances, sometimes completely unexpected, have the ability to relax the muscles of the uterus. The classification does not make much sense, let's name only those drugs that are used most often.
β2-adrenostimulants are the most commonly used tocolytic drugs such as ginipral, salbutamol, and partusisten. Doctors prescribe them to maintain pregnancy, as they suppress the contractile activity of the uterus. In addition, they are widely used to improve uteroplacental blood flow while eliminating or preventing hypoxia in a child.
These tocolytic drugs affect not only the uterus, there are receptors for them in many organs and tissues, which is why when taking ginipral, for example, there may be tachycardia and a decrease in blood pressure, and salbutamol is one of the most famous remedies for bronchial asthma.
Magnesium sulfate, or magnesia, is familiar to many pregnant women. The tocolytic effect of this drug is based on the suppression of the flow of calcium ions into the smooth muscle cells of the myometrium, which reduces the contractile activity of the uterus. Magnesia is used intramuscularly, usually in the second half of pregnancy.
Unfortunately, wear-pa, papaverine and other antispasmodics have almost no effect on the pregnant uterus and their use is ineffective. Tocolytics have a completely different mechanism of action and, of course, their doctors prescribe to pregnant women.
Active research is now underway on nifedipine and other calcium ion antagonists (these drugs are used to lower blood pressure, but they also affect the myometrium). Also, drugs are being developed that suppress the synthesis of prostaglandins, as you know, these substances play a huge role in the development of contractions.
With the threat of termination of pregnancy, gestagens are often prescribed (pregnin, duphaston, narcolut, progesterone, turinal, etc.), these drugs do not have a tocolytic effect by themselves, but they can suppress the sensitivity of the uterus itself to other substances that cause its contractile activity.
Tokomimetics
The opposite of tocolytics are tokomimetic drugs. Tokomimetics act only on the muscles of the uterus, causing its contractile activity. They are used to induce labor and are drugs that induce and intensify contractions.
For this purpose, oxytocin and its analogs (the hormone of the posterior lobe of the pituitary gland) are prescribed, but it works only in the second half of pregnancy, and the maximum sensitivity of the uterus to oxytocin is achieved only at term. Oxytocin not only stimulates labor but also induces milk production by affecting lactation.
Other tokomimetics are drugs - prostaglandin analogs. They are effective at any stage of pregnancy, cause contractions of the uterus and accelerate the maturation of its cervix. Prostaglandins cause uterine contraction even in non-pregnant women, and reduce the sensitivity of the myometrium to tocolytics.
Dinoprostone and dinoprost, analogs of prostaglandins PGE2 and PGF2a, respectively, have a tokomimetic effect.
Prostaglandins are widely used not only to stimulate labor during full-term pregnancy, they are used for medical abortion, and for the expulsion of the fetus with a frozen pregnancy, including at a later date.
Ministry of Health of UkraineGZ "Lugansk State Medical University"
Department of Obstetrics, Gynecology and Perinatology FPO
Head of the Department: Doctor of Medical Sciences, Prof. Lubyanaya S.S.
Lecturer: Ass. Lytkin R.A.
REPORT
"Tocolytic therapy"
Prepared by: 5th year student, group number 21
II Faculty of Medicine
Specialty: "Pediatrics"
Chudnovsky A.A.
Luhansk 2011
Premature birth is one of the leading causes of neonatal morbidity and mortality. In developed countries of the world, preterm birth is responsible for up to 80% of neonatal mortality not associated with congenital malformations of the fetus (Rush et al., 2005).
Since 2007, Ukraine has switched to the criteria for the registration of the perinatal period in accordance with the recommendations of the WHO (Order of the Ministry of Health of Ukraine No. 179 dated March 29, 2006 "On the consolidated instructions for the establishment of criteria for the perinatal period, live birth and still birth, according to which the order of pre-pregnancy" childbirth with a spontaneous onset, the progression of labor and the birth of a fetus weighing more than 500 g, occurring from the 22nd full week to the end of the 37th week of pregnancy, are considered. The frequency of preterm birth in Ukraine, taking into account the new criteria, ranges from 12% to 46%.
For obstetricians-gynecologists, there is an acute issue of prolongation of pregnancy in patients at risk of premature birth, as well as optimization of the tactics of managing such births. In world practice, tocolytic drugs with different mechanisms of action are used to solve these problems. Influence medicines on the uterus can be both direct and mediated. The main links to which the action is directed drugs with premature maturation, are: regulation of the level of sex hormones, the effect on adrenergic, cholinergic, serotonergic receptors, as well as changes in the level of oxytocin, prostaglandins, melatonin, kinins, histamine, the effect on the activity of phosphodiesterase, ionic conductivity of myocyte membranes (in particular, Ca2 + and K + ), changes in the content of relaxin, etc.
Strategy and tactics of therapy
The goal of tocolytic therapy (TT) is to prolong pregnancy:
For at least 48 hours to carry out corticosteroid prophylaxis of respiratory distress syndrome of the fetus and reduce the risk of developing necrotizing enterocolitis and intracranial hemorrhage;
For the time required to transport the patient to a specialized hospital;
If the risk of its interruption develops against the background of another pathology (gestational pyelonephritis, after surgical interventions, injuries);
Until the term of fetal viability (34 weeks).
The main tasks of tocolytic therapy:
1. Delay childbirth for the possibility of glucocorticoid therapy in order to reduce the incidence of respiratory distress syndrome (RDS) and timely hospitalization of the pregnant woman in the perinatal center in the neonatal intensive care unit;
2. Delay delivery to ensure growth and maturation of the fetus and a possible reduction in perinatal morbidity and mortality
Tocolytic therapy, as a rule, is ineffective when the uterine pharynx opens by 3 cm or more. However, even in this situation, tocolysis is necessary for prophylaxis with corticosteroids.
Long-term tocolysis has a beneficial effect on the feto-placental system and can reduce the rate of loss amniotic fluid, depending to a certain extent on the tone of the myometrium. Long-term tocolytic therapy is indicated up to 31 weeks of gestation in the absence of indications for urgent (emergency) delivery. In later stages of pregnancy, tocolysis is indicated for the period of drug prevention SDR of the fetus.
Features of TT
1. Monotherapy. The following procedure for prescribing drugs is recommended. Treatment begins with beta-adrenostimulants or magnesium sulfate. If neither is effective, NSAIDs or calcium antagonists are prescribed. Despite reports on the effectiveness of tocolytic agents of the listed groups, none of them has been studied enough to become the drug of choice.
2. Combined therapy with tocolytic agents is indicated only in the most extreme cases, for example, during pregnancy up to 28-30 weeks with the ineffectiveness of monotherapy and the dilatation of the cervix by more than 2-3 cm. Prolongation of pregnancy by at least 2 days in this case allows to accelerate maturation lungs of the fetus and significantly reduce the risk of death of the newborn. It has been shown that each additional day of intrauterine stay at 25-28 weeks of gestation significantly increases the viability of the newborn. With the simultaneous appointment of several tocolytic agents, the woman is explained in detail likely consequences as well as the possibility of other treatments.
Tocolytic drugs are often ineffective due to infection. With chorioamnionitis, tocolytic therapy is contraindicated. For other infections, such as pyelonephritis, tocolytic therapy is acceptable, but this increases the risk of ARDS. For the prevention of ARDS, the intake and administration of fluids is limited (up to 100 ml / h). When treated with corticosteroids for 24-36 hours, leukocytosis can be observed up to 30,000 μl – 1 with a shift leukocyte formula to the left. If the level of leukocytes is more than 30,000 µl – 1, infection is excluded.
a. There is no ideal combination of tocolytic agents. The most effective combination of indomethacin with magnesium sulfate or ritodrin. The use of ritodrin in combination with magnesium sulfate was also reported, however, the effectiveness of this scheme did not differ significantly from that when using each drug separately. Calcium antagonists are not recommended to be combined with other drugs.
b. The simultaneous appointment of three tocolytic agents is not recommended, since this significantly increases the risk of complications without increasing the effectiveness of treatment.
3. ARDS is a common complication of tocolytic therapy. It was previously thought to be due to the use of corticosteroids to accelerate fetal lung maturation, but research has shown that the main cause of ARDS in preterm labor is infection. Prevention includes fluid restriction. The total fluid intake (by mouth and IV) should not exceed 100-125 ml / h or approximately 2.0-2.5 l / day. When treated with tocolytic agents for infusion therapy use 5% glucose or 0.25% NaCl.
Contraindications to the appointment of TT
Contraindications to the use of tocolytics - thyrotoxicosis, glaucoma, diabetes mellitus, cardiovascular diseases (aortic stenosis, idiopathic tachycardia, cardiac arrhythmias, congenital and acquired heart defects), intrauterine infection or suspicion of it, polyhydramnios, bleeding, placenta previa premature detachment of the normally located placenta, fetal heart rhythm disturbance, fetal deformities, suspected inconsistency of the uterine scar.
Classification
Currently, some success has been achieved in the treatment of threatening preterm labor due to drugs that suppress the contractile activity of the uterus, which include tocolytics. Among them, the following main groups can be distinguished: β2-adrenomimetics, α2-adrenomimetics, neurotropic and myotropic antispasmodics, antagonists of calcium ions, magnesium sulfate, purinergic receptor blockers, GABA-ergic drugs, phosphodiesterase inhibitors, antagonists of serotonin receptor blockers, antibiotics, antagonists oxytocin receptors, potassium channel activators, nitrates, as well as drugs that indirectly inhibit uterine contractile activity (progesterone, relaxin, melatonin), inhibitors of prostaglandin biosynthesis, oxytocin release, benzodiazepine receptor antagonists.
In practical obstetrics, magnesium sulfate is often used. Although the mechanism of action of Mg2 + ions on smooth muscle is not completely established, it is believed that they are capable of influencing the process of interaction of agonists with the receptor, ion permeability plasma membrane myocytes, modulate intracellular signaling. Mg2 + ions can also slow down the release of Ca2 + from the intracellular depot, thereby reducing the tone and contractile activity of the myometrium. An increase in the extracellular concentration of Mg2 + ions enhances the contraction of smooth muscles of the myometrium, induced by oxytocin. An important aspect of the use of magnesium sulfate in obstetric practice is that the drug has an anticonvulsant effect, which makes it possible to use it for the treatment of preeclampsia and eclampsia, as well as a low probability of overdose, which is also easily eliminated by the administration of calcium gluconate. With the threat of premature birth, the prophylactic use of magnesium sulfate as monotherapy has a less pronounced effect.
Despite the fact that the experience of using magnesium sulfate goes back more than one decade, in last years published a number of reports of serious side effects observed with its use. Long-term monitoring showed that quite often after administration of the drug there is a dose-dependent decrease in the heart rate (HR) of the fetus, which is a consequence of sinus bradycardia of the fetus. On cardiotocograms, a significant decrease in slow and short-term heart rate variability is recorded, a decrease in the total oscillations. There is evidence that the introduction of magnesium sulfate is accompanied by significant changes in fetal hemodynamics: in the middle cerebral artery, the blood flow rate in diastole decreases. The stroke volume of the right ventricle of the fetus decreases, and that of the left - increases, which leads to an increase cardiac output... Severe changes in the brain in the form of periventricular leukomalacia without or with grade III and IV intraventricular hemorrhages were recorded by neurosonographic analysis in newborns. After a prolonged (more than 6 weeks) use of magnesium sulfate for the purpose of tocolysis, the pathology of the metaphyses of long bones is revealed by x-ray, which is eliminated during the first year of life. The nature of the pathology and its severity depend not only on the dose of magnesium sulfate and the duration of use, but also on the duration of pregnancy in which the drug was used. Starting from the second trimester of pregnancy, long-term infusions can cause suppression of function. parathyroid glands fetus with the subsequent development of rickets-like conditions. In the mother's body, after prolonged use of magnesium sulfate, violations of calcium homeostasis are noted: density decreases bone tissue, hypercalciuria, osteoporosis develop, bleeding time increases, neuromuscular transmission is disrupted.
Of the earlier drugs to reduce the contractile activity of the uterus, the following were used: nervous system(valerian, trioxazine, pipolfen, etc.), antispasmodics, sedatives, anticholinergics, vitamins E and A. In the presence of tangible uterine contractions, suppositories with papaverine and magnesium sulfate were used. Magnesium electrophoresis and endonasal galvanization were used. Progesterone was used, with a reduced function of the corpus luteum and a lack of this hormone.
Agonists
b-adrenergic receptors
The effectiveness of the use of b-adrenergic agonists in the treatment of the threat of preterm labor has been proven on the example of ritodrin, terbutaline and hexoprenaline both in many foreign studies and in our country. However, the use of rithodrin, according to the FDA recommendations in the United States, is currently on hold.
The mechanism of action of drugs in this group is based on the relaxation of the uterine muscles under the influence of stimulation of b2-adrenergic receptors and an increase in the concentration of intracellular adenylate cyclase. As a result, protein kinases are activated and the processes of intracellular phosphorylation are accelerated, which leads to blocking the interaction of free calcium inside the cell with actin and myosin filaments and relaxing the muscles.
The use of b-adrenergic tocolytics promotes prolongation of pregnancy by 72 hours or more, but does not significantly affect the incidence of preterm birth and perinatal morbidity.
Under certain circumstances, the use of b-mimetics poses some risk to the mother and fetus. From the mother's side the most frequent complications are headache, anxiety, tremor, increased sweating, tachycardia, in rare cases, nausea and vomiting develop. In patients with bronchial asthma and hypersensitivity to sulfites, taking medications can cause allergic reactions, the possible symptoms of which are diarrhea, shortness of breath, impairment and loss of consciousness, bronchospasm or anaphylactic shock... A decrease in blood pressure (BP), especially diastolic pressure, is possible. In rare cases, the appearance of ventricular extrasystoles, complaints of pain in the region of the heart (cardialgia) has been noted. These symptoms disappear quickly after stopping the drug. The glycogenolytic effect of the drug is manifested by an increase in blood sugar content; in diabetes mellitus, this effect is more pronounced. Diuresis, especially at the beginning of treatment, decreases. Hypokalemia and hypocalcemia often develop at the beginning of therapy, but in the course of further treatment, the content of potassium and calcium is normalized. A temporary increase in the concentration of transaminases in the blood serum is possible. Inhibition of intestinal motility may occur. In rare cases, intestinal atony is observed, therefore, with tocolytic therapy, attention should be paid to the regularity of the stool.
On the part of the fetus, due to the penetration of b-mimetics through the placenta, tachycardia, fetal hypoglycemia associated with maternal hyperinsulinemia may develop. The connection between the use of tocolytics and the risk of intraventricular hemorrhage in the fetus remains controversial. Most modern studies indicate that the use of β-adrenergic receptor agonists reduces the risk of developing this complication in the fetus and newborn, but the opposite data remains.
Taking b-mimetics is contraindicated for: hypersensitivity to one of the components of the drug (especially in patients suffering from bronchial asthma and hypersensitivity to sulfites); thyrotoxicosis; cardiovascular diseases, especially in violation of the rhythm of the heart, occurring with tachycardia, myocarditis, mitral valve disease and aortic stenosis; ischemic disease hearts; severe liver and kidney diseases; arterial hypertension; angle-closure glaucoma; uterine bleeding, premature placental abruption; intrauterine infections; I trimester of pregnancy; during lactation. Care should be taken to prescribe b-mimetics to patients with a high risk of bleeding, for example, in the case of placenta previa, since it has been proven that with the development of tachycardia in the mother, the risk of bleeding with abnormal localization of the placenta increases significantly.
Gynipral
Synonyms: Hexoprenaline.
Pharmachologic effect. In connection with the influence on the 6a2-adrenergic receptors of the uterus, it has a tocolytic (relaxing the muscles of the uterus) effect. Corresponds to the drug hexoprenaline.
Indication for use. It is used as a tocolytic agent with the threat of premature birth (in the third trimester of pregnancy), with acute intrauterine fetal asphyxia (impaired blood supply to the fetus), during childbirth (with discoordinated labor - improper contractions of the uterus during childbirth), to suppress uterine contractions before surgery intervention (dissection of the cervix, cesarean section).
Method of administration and dosage. Ginipral is used intravenously and inside (in tablets). A "shock" dose (in acute cases) is injected intravenously slowly - 5-10 μg of ginipral in 10-20 ml of isotonic sodium chloride solution. For infusions (with long-term treatment), dilute 50 μg (contents of 2 ampoules of 25 μg each - "concentrate" of ginipral) in 500 ml of 5% glucose solution. Injected at a rate of 25 drops per minute (about 0.125 μg per minute). If necessary, the dose is increased by 5 drops every 5 minutes. The minimum injection rate is 10 drops per minute, the maximum injection rate is 60 drops per minute.
The tablets begin to be taken 2-3 hours before the end of the parenteral (intravenous) administration. First, 1 tablet is prescribed, then after 3 hours, 1 tablet every 4-6 hours; only 4-8 tablets per day.
Side effect. Headache, anxiety, tremors (tremors of the limbs), sweating, dizziness are possible. Rarely - nausea, vomiting. There are isolated reports of intestinal atony (loss of tone); an increase in the content of serum transaminases (enzymes). An increase in the mother's heart rate, a decrease in blood pressure, especially diastolic ("lower" blood pressure), is possible. In several cases, ventricular extrasystoles (cardiac arrhythmias) and complaints of pain in the region of the heart were observed. These symptoms disappear after stopping treatment. The fetal heart rate in most cases does not change or changes little. An increase in the concentration of glucose (sugar) in the blood. This effect is more pronounced in patients with diabetes mellitus. Decreased urine output (urination), especially in the initial phase of treatment. During the first few days of treatment, a decrease in the concentration of calcium in the blood plasma is possible; in the course of further treatment, the calcium concentration is normalized.
Contraindications Thyrotoxicosis (thyroid disease); cardiovascular diseases, especially tachyarrhythmia (heart rhythm disturbance), myocarditis (inflammation of the heart muscles), mitral valve lesions, idiopathic hypertrophic subaortic stenosis (non-inflammatory disease of the muscle tissue of the left ventricle of the heart, characterized by a sharp narrowing of its cavity); severe kidney and liver disease; angle-closure glaucoma (increased intraocular pressure); heavy uterine bleeding; premature detachment of the placenta; infectious lesions of the endometrium (inner lining of the uterus); hypersensitivity to the drug, especially in patients with bronchial asthma.
Release form. In ampoules containing 0.025 mg or 0.01 mg each; tablets of 0.5 mg.
Isoxuprine (Isoxsuprine)
Synonyms: Duvadilan.
Pharmachologic effect. It has a tocolytic (relaxing the muscles of the uterus) effect by stimulating beta-adrenergic receptors. Reduces the tone of the smooth muscles of the blood vessels of skeletal muscles, eliminates spasm (sharp narrowing of the lumen) of the vessels, increases the blood supply to tissues
Indication for use. Threat of premature birth, obliterating endarteritis (inflammation of the inner lining of the arteries of the extremities with a decrease in their lumen), Raynaud's disease (narrowing of the lumen of the vessels of the extremities), spasm of peripheral vessels.
Method of administration and dosage. With the threat of premature birth, intravenous drip infusion is prescribed (100 mg of the drug per 500 ml of 5% glucose solution) at a rate of 1-1.5 ml / min; the rate of administration is gradually increased to 2.5 ml / min. When the condition improves (cessation of contractions), they switch to intramuscular administration of the drug: within 24 hours - 10 mg every 3 hours. In the next 48 hours, 10 mg every 4-6 hours. After that, within 2 days, isoxsuprine is prescribed orally, 20 mg 4 times a day. In diseases of peripheral vessels, it is prescribed orally at 20 mg 4 times a day. In more severe cases, intravenous drip administration is prescribed (20 mg of the drug per 100 ml of 5% glucose solution) at a rate of 1.5 ml / min 2 times a day. Intramuscular administration of the drug, 10 mg 3-4 times a day, is also possible.
Side effect. Tachycardia (increased heart rate), hypotension (lowering blood pressure), dizziness, flushing of the upper half of the body, to the face with parenteral administration (intravenous and intramuscular); nausea, vomiting, rash.
Contraindications Recent bleeding, hypotension (low blood pressure), angina pectoris.
Release form. Tablets of 0.02 g of isoxsuprine hydrochloride in a package of 50 pieces; solution for injection (in 1 ml 5 mg of isoxsuprine hydrochloride) in 2 ml ampoules in a package of 6 pieces.
Storage conditions. List B. In a cool place.
PARTUSISTEN (Partusisten)
Synonyms: Fenoterol.
Pharmachologic effect. It has a tocolytic (relaxing the muscles of the uterus) effect. Belongs to the group of beta2-adrenostimulants. Corresponds to the drug fenoterol.
Indication for use. The experience of using partusisten shows that it is an effective tool for eliminating the threat of premature birth and does not adversely affect the fetus and newborn.
Method of administration and dosage. Assign intravenously (drip) and inside in the form of tablets. Soon after the start of intravenous administration, there is usually a significant decrease in pain, the tension of the uterus is relieved, then the pain and contractions of the uterus completely stop.
Inside take 5 mg every 2-3 hours; the daily dose is up to 40 mg. With increased sensitivity (the appearance of tachycardia / increased heart rate /, muscle weakness, etc.), a single dose is reduced to 2.5 mg, and the daily dose is reduced to 30 mg. The duration of the course of treatment is 1-3 weeks. Intravenous drip (0.5 mg in 250-500 ml of 5% glucose solution) is injected at 15-20 drops per minute until the contraction of the uterus is inhibited.
Partusisten is used in specialized medical institutions under close medical supervision.
Side effect. The drug can cause tachycardia, tremors (tremors) of the hands, muscle weakness, decreased blood pressure, sweating, nausea, and vomiting. It is noted that side effects are reduced under the influence of verapamil - 30 mg intravenously.
Contraindications Heart defects, cardiac arrhythmias, thyrotoxicosis (thyroid disease), glaucoma (increased intraocular pressure).
Release form. Ampoules of 0.025 mg; tablets of 0.5 mg.
RITODRIN (Ritodrinum)
Synonyms: Prempar, Pre-Par, Yutopar.
Pharmachologic effect. The action is close to fenoterol, salbupart and other beta2-adrenergic agonists.
Indication for use. It is used as a tocolytic (relaxing the muscles of the uterus) means with the threat of premature termination of pregnancy.
Method of administration and dosage. Inside appoint 5-10 mg 4-6 times a day. Usually, at these doses, uterine contractions stop and the possibility of maintaining pregnancy increases. The duration of the drug is 1-4 weeks. With the onset of preterm labor, oral (through the mouth) use is not effective enough and the drug is administered intravenously; To do this, dilute 50 mg of the drug in 500 ml of isotonic sodium chloride solution and inject it drip, starting at 10 drops per minute, then gradually increase the rate of administration (15 drops) until the uterus is completely relaxed. To continue the effect, the drug is administered intramuscularly at 10 mg every 4-6 hours, after which it is administered orally at 10 mg 4-6 times a day with a gradual dose reduction.
Ritodrin, as well as partusisten, is used in specialized medical institutions.
Side effects and contraindications. Possible side effects and precautions are the same as with Partusisten.
Release form. 5 mg tablets; ampoules of 10 mg.
Storage conditions. List B. In the dark place.
SALBUPART
Synonyms: Salbutamol, Ventolin, Ekovent, etc.
Pharmachologic effect. By its action on the contractile activity of the uterus, salbupart is close to partusisten. Refers to beta2-adrenostimulants. Corresponds to the drug salbutamol.
Indication for use. It is used as a tocolytic (relaxing the muscles of the uterus) means to eliminate the threat of premature birth, as well as after operations on the pregnant uterus.
Method of administration and dosage. Introduced intravenously. The contents of one ampoule (5 mg) are diluted in 400-500 ml of isotonic sodium chloride solution or 5% glucose solution. Enter at a rate of 15-20 drops (starting with 5 drops) per minute. The rate of administration depends on the intensity of uterine contractions and tolerance (monitor heart rate and other hemodynamic parameters). Duration of administration is 6-12 hours.
Release form. 0.1% solution in capsules of 5 ml (5 mg).
Storage conditions. List B. In the dark place.
TERBUTALIN (Terbutalin)
Synonyms: Brikanil, Arubendol, Betasmak, Brika-lin, Brikan, Brikar, Drakanil, Spiranil, Terbutol, Tergil, etc.
Pharmachologic effect. In terms of pharmacological properties, it is close to salbutamol. It has a tocolytic (relaxing the muscles of the uterus) effect.
Indication for use. Used as a tocolytic (relaxing the muscles of the uterus) means to eliminate the threat of premature birth.
Method of administration and dosage. As a tocolytic agent (in obstetric practice), it is used in the form of drip intravenous infusions (10-25 μg per minute in an isotonic solution of glucose or sodium chloride) with a further transition to subcutaneous injections (250 μg = 1/2 ampoule) 4 times in day for 3 days. At the same time, 5 mg is administered orally 3 times a day.
Side effects and contraindications are the same as for partusisten.
Release form. Tablets of 0.0025 g (2.5 mg) in a package of 20 pieces; 0.05% solution (0.5 mg) of terbutaline sulfate in ampoules containing 1 ml each, in a package of 10 ampoules.
Storage conditions. List B. In the dark place.
TROPACIN (Tropacinum)
Synonyms: Diphenyltropine hydrochloride, Tropazine.
Pharmachologic effect. In terms of pharmacological properties, tropacin is close to atropine (see page 92). In obstetric practice, it is used as an antispasmodic (relieving spasms) agent that inhibits the contractile activity of the uterus.
Indication for use. As a tocolytic (relaxing the muscles of the uterus) a remedy for the threat of premature birth and abortion.
Method of administration and dosage. As a tocolytic agent inside 0.02 g 2 times a day.
Side effects and contraindications
Release form. Tablets 0.001; 0; 003; 0.005; 0.01; 0.015 g in a package of 10 pieces.
Storage conditions. List A. In a well-closed container, protected from light.
Calcium channel blockers
The mechanism of action of the drugs is based on blocking the penetration of calcium ions into the cell. In addition, the drugs promote the excretion of intracellular calcium and the cytoplasmic reticulum and its excretion from the cell.
In the available literature, there are many different comparative studies of the effectiveness of drugs in the treatment of threatened preterm birth. A meta-analysis of 12 such randomized, placebo-controlled trials, involving more than 1000 women, was presented in 2009. Calcium channel blockers were not more effective for acute tocolysis than β-mimetics and magnesium therapy (RR 0.80; 95% CI 0.61–1.05), however, long-term therapy for 7 days had a more pronounced effect (RR 0.76; 95% CI 0.60–0.97). In addition, the use of calcium channel blockers has been shown to reduce the risk of developing respiratory distress syndrome (RR 0.63; 95% CI 0.46–0.88), necrotizing enterocolitis (RR 0.21; 95% CI 0.05– 0.96), intraventricular hemorrhage (RR 0.59; 95% CI 0.36–0.98) and neonatal jaundice (RR 0.73; 95% CI 0.57–0.93).
In recent decades, both foreign and domestic researchers have accumulated significant experience in the use of calcium channel blockers in obstetric practice, primarily in diseases accompanied by an increase in blood pressure (hypertension, preeclampsia), as well as with the threat of termination of pregnancy. Common in the pathogenesis of these diseases is an increase in the tone and contractile activity of smooth muscles due to an increase in the concentration of free calcium (Ca2 +) in smooth muscle cells, which enters through the receptor and voltage-dependent calcium channels. Blocking the latter reduces the contractile activity of vascular smooth muscles and myometrium.
However, the use of calcium channel blockers as tocolytic agents in premature pregnancy is often accompanied by unwanted effects: flushing of the face, tachycardia and arterial hypotension. In high doses, the drugs disrupted antrioventricular conduction and increased the fetal heart rate. The use of calcium channel blockers is contraindicated in patients with hypersensitivity to drugs in this group and with left myocardial dysfunction. In addition, the combined use of calcium channel blockers and magnesium therapy has a synergistic effect and leads to respiratory arrest. Side effects from the use of drugs on the part of the mother are most often a decrease in blood pressure due to peripheral vasodilation, nausea, fever, headache and dizziness, on the part of the fetus - a decrease in uterine, umbilical cord blood flow and O2 saturation in fetal blood.
Unfortunately, there are no clear developments on the dosage of drugs. Nifedipine is usually given at an initial dose of 30 mg orally or 10 mg every 20 minutes 4 times. According to the strength of the inhibitory effect on the uterus, these drugs were arranged as follows: nitrendipine, nicardipine, nifedipine, verapamil, diltiazem.
Progesterone , although not a tocolytic in the direct sense of the word, is increasingly used in the protocols of tocolytic therapy for preterm labor. The close relationship of progesterone production with miscarriage has been known for a long time, and the use of this drug with the threat of termination of pregnancy has been going on for more than a dozen years. And only in recent years, the main (primarily immune) mechanisms of the implementation by gestagens of their protective function in relation to the fetus. The concentration of progesterone in the blood and urinary excretion of its main metabolite - pregnandiol begin to increase from the moment of ovulation in the cycle of conception and further progressively increase during physiological pregnancy, reaching a maximum by the 36th week. First, the hormone is formed in corpus luteum, and in the later stages of pregnancy - mainly in the placenta. About 30% of the secreted progesterone goes to the fetus, and this amount can increase with fetal pathology (in particular, with stress, chronic hypoxia and fetal malnutrition). Since the fetus is immunologically foreign to the mother's body, during pregnancy, rather complex and not fully studied phylogenetic mechanisms of immunomodulation are formed, aimed at protecting the fetus. At normal pregnancy physiological increase in progesterone production induces the formation of receptors for both progesterone itself and PIBF; thus, this hormone participates in the immune mechanisms of the embryo's defense, maintenance and preservation of pregnancy.
After implantation, simultaneously with an increase in progesterone secretion, there is a natural change in the level of progesterone receptors, which is noted not only in the decidual tissue, but also in the myometrium: the concentration of nuclear receptors increases, and the cytosolic receptor decreases. The presence of a sufficient level of progesterone and its receptors ensures the functioning of the mechanisms involved in suppressing the tone of the uterus and its contractile activity. So, progesterone reduces the synthesis of prostaglandins in the uterus, and the main metabolite of progesterone - 5α-pregnandiol, blocking oxytocin receptors, reduces the sensitivity of the myometrium to oxytocin and prostaglandin F2α, the number of α-adrenergic receptors in it. The inhibition of the latter occurs without their simultaneous modification, as a result of which the expression of α-adrenergic receptors becomes dominant. This circumstance allows, against the background of the use of progesterone, to significantly reduce the doses of β2-adrenergic agonists used, which is important in practical terms, since it makes it possible to avoid the side effects characteristic of β2-adrenergic agonists while maintaining their therapeutic benefits.
It is equally important that sufficient levels of progesterone ensure the maintenance of the appropriate ultrastructural organization of the myometrium - the formation of intercellular gap junctions in it, through which impulses are transmitted, is prevented. This makes it difficult to generalize the contraction of individual muscle fibers in the contraction of the entire uterus in response to various types of its stimulation. Due to the antiandrogenic activity of progesterone, it is able to protect the female fetus from androgens synthesized in the maternal body, the level of which increases during pregnancy and significantly exceeds physiological values in diseases such as polycystic ovary syndrome, congenital hyperplasia adrenal cortex.
Cyclooxygenase inhibitors
The mechanism of action of inhibitors of cyclooxygenase (COX) is the block of synthesis of prostaglandins from arachidonic acid.
Indomethacin is the most commonly used non-specific COX inhibitor. The Cochrane database has reports of more effective use indomethacin in the treatment of threatened preterm labor compared with placebo within 48 hours (RR 0.20; 95% CI 0.03-1.28) and 7 days of therapy (RR 0.41; 95% CI 0.10-1, 66). There were no differences in perinatal outcomes.
Side effects from the use of COX inhibitors are well studied on the part of the mother (nausea, isophageal reflux, gastritis) and develop in about 4% of cases. From the side of the fetus, it is also possible to develop side effects, the most significant of which are premature closure. arterial duct(with development pulmonary hypertension) and lack of water. However, the frequency of these complications does not exceed 1: 500. It has been shown that the risk of closure of the ductus arteriosus increases with prolonged use of indomethacin for 31–32 weeks, and therefore the use of COX inhibitors is not allowed after 32 weeks of gestation. Other rare complications from the fetus can be bronchopulmonary dysplasia, necrotizing enterocolitis, leukomalacia, intraventricular hemorrhage.
Contraindications for the use of COX inhibitors are platelet dysfunctions and bleeding, liver and kidney pathology, peptic ulcer stomach and bronchial asthma.
The dosage of indomethacin in the treatment of preterm labor is from 50 to 100 mg rectally, and then 25 mg orally every 4-6 hours (therapeutic dose 1000 mg). If it is necessary to reuse, the interval between the administration of the drug should be at least 14 days.
Antagonists
oxytocin receptors
These drugs are not available for use in Ukraine, but are widely used in Europe. Atosiban is a selective antagonist of oxytocin-vasopressin receptors and is theoretically more effective when used later in pregnancy, when the density and sensitivity of receptors to oxytocin in the myometrium are significantly increased.
The Cochrane database has reported 6 randomized trials of 1,695 women at risk of preterm birth who received atosiban or placebo. On the background of drug therapy, the risk of preterm birth increased in the first 48 hours of therapy (RR 2.50; 95% CI 0.51-12.35) and before 28 weeks of pregnancy (RR 2.25; 95% CI 0.80– 6.35).
There were no specific maternal side effects. From the side of the fetus, it was shown that the drug crosses the placenta, and there were also several reports of intrauterine fetal death at 26 weeks of gestation. The most common side effect is injury of cardio-vascular system... In addition, atosiban is also known to block fetal receptors, which can interfere with fetal kidney and lung development.
There are no absolute contraindications to the use of the drug. Some authors recommend that you refrain from using atosiban until 28 weeks of gestation.
The drug is administered intravenously bolus at a dose of 6.75 mg, then at a rate of 300 mcg / min with an infusomat, upon reaching the clinical effect, the dose is reduced to 100 mcg / min and therapy continues for 45 hours.
Tractocila ( active substance- atoshiban).
Tractocil is a selective antagonist of oxytocin receptors, which has a specific tropism for uterine receptors, which reduces the frequency of its contractions and slows down the contractile activity of the myometrium
Nitric oxide donors
The mechanism of action of nitric oxide (NO) is muscle relaxation due to an increase in the production of 3,5-guanosine monophosphate. At present, there is still not enough data on the effectiveness of the use of NO donors in the treatment of preterm labor. Several studies are presented in which patients received transdermal nitroglycerin in comparison with β-mimetics or magnesium sulfate at 24 to 32 weeks of gestation. It was shown that nitroglycerin suppresses uterine activity to a lesser extent than b-mimetics, and is inferior in effectiveness to magnesium preparations.
Maternal side effects were hypotension, hot flashes, dizziness, and palpitations. With a decrease in maternal blood pressure, a decrease in uterine blood flow was also noted, however, there were no side effects from the fetus. Contraindication to the use of the drug is arterial hypotension, aortic insufficiency.
The drugs can be administered transdermally or intravenously, but dosage recommendations are not yet available. On average, 10 mg of glyceryl trinitrate is applied to the abdominal skin. In the absence of a pronounced effect, the procedure is repeated after 1 hour. When administered intravenously, a dose of 20 μg / min is acceptable and justified until a clinical effect is achieved.
Conclusion:
So, despite the rather wide range drugs used for the purpose of tocolysis, the appropriateness of their use, efficacy and safety for both the mother and the fetus are ambiguous. Tocolytic drugs can delay labor for a short time, however, there is a danger of them toxic effects on the mother's body in the form of hypotension, tachycardia, fluid retention. There is no conclusive evidence for the effectiveness of oral tocolytics and their supportive tocolytic therapy.
The use of tocolytics for deep premature pregnancy makes it possible to gain time sufficient for antenatal use of steroids or hospitalization of a woman in a specialized perinatal center. After the 34th week of pregnancy, the appointment of tocolytic drugs is inappropriate, since children are born viable, and the risk of complications against the background of this therapy significantly exceeds real benefit from its application.
In most cases, it is advisable to prescribe tocolysis for 48-72 hours to prevent RDS, then tocolytics are canceled and follow-up is continued. Once labor has begun, it is no longer blocked.
In conclusion, I would like to note that the choice of a drug for the therapy of preterm labor is strictly individual and depends on the duration of the complication, its severity and the patient's history. B-mimetics are the first line drugs worldwide.
Literature
1. Obstetrics: National guidelines. Ed. V.I.Kulakov, G.M.Savelieva, V.E. Radzinsky, E.K. Aylamazyan
2. Cordero L, Nankervis CA, Gardner D, Giannone, PJ. The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants. J Perinatol 2007; 27:22.
3. Amin SB, Sinkin RA, Glantz JC. Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes. Am J Obstet Gynecol 2007; 197: 486.
4. Groom KM, Shennan AH, Jones BA et al. TOCOX-A randomized, double-blind, placebo-controlled trial of rofecoxib (a COX-2-specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk. BJOG 2005; 112: 725.
5. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologist. Number 43, May 2003. Management of preterm labor. Obstet Gynecol 2003; 101: 1039.
6. Lyell DJ, Pullen K, Campbell L et al. Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial. Obstet Gynecol 2007; 110: 61.
7. Mittendorf R, Dambrosia J, Pryde PG et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol 2002; 186: 1111.
8. Marret S, Marpeau L, Zupan-Simunek V et al. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomized controlled PREMAG trial *. BJOG 2007; 114: 310.
9. Stika CS, Gross GA, Leguizamon G et al. A prospective randomized safety trial of celecoxib for treatment of preterm labor. Am J Obstet Gynecol 2002; 187: 653.
10. Goldenberg RL. The management of preterm labor. Obstet Gynecol 2002; 100: 1020.
11. Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med 2007; 357: 477.
Catalog: media -> abstract
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abstract -> Abstract
In the past, obstetricians have tried several dozen drugs for stopping premature birth and maintaining pregnancy in the second and third trimester. Majority remedies not accepted for use due to serious side effects of such drugs and possible harm to the fetus. It is hard to believe that alcohol was used to stop preterm labor in the last century, but now it is a historical fact.
Modern medicine has about sixty serious clinical studies on tocolytic therapy, not to mention a huge number (several hundred) small studies... The use of tocolytics is actual topic, since for many years doctors have been looking for a "panacea" so that they can get the desired result with the least negative impact on the mother and fetus. But such a panacea was not found. Moreover, having examined those drugs that were used in obstetrics with or without caution, doctors realized with considerable concern that most drugs could not be used. It turned out that it is not so easy to prevent or stop premature birth, and if this is possible, then it is possible to prolong the pregnancy only by 2-7 days, and very rarely until the calendar date.
Magnesium sulfate (magnesia), indomethacin and nifedipine remained in the arsenal of modern obstetrics.
The oldest and most common drug is magnesium sulfate solution - magnesia... Unlike other drugs, magnesium is more toxic to the mother and safer for the fetus. Most often, it causes nausea, hot flashes, headache, dizziness, blurred vision, in worst cases, impaired respiratory and cardiac functions. The most dangerous complication is pulmonary edema. Magnesium sulfate crosses the placenta and can cause respiratory impairment in newborns if this drug was used to stop labor, but unsuccessfully.
It is very unpleasant that magnesium is given intravenously to almost every pregnant woman (worst of all - in the early stages of pregnancy), and day hospitals where such women go, have become the cry of the latest "obstetric fashion", a kind of cultivator of all kinds of rumors, myths, prejudices and fears. This drug does not work on or suppress the uterus contractile function in the early stages of pregnancy, therefore, should not be prescribed to everyone who has been diagnosed with uterine hypertonicity by ultrasound or who has something in the lower abdomen somewhere. The development of side effects is much more dangerous than the nonexistent benefits from the use of magnesia.
The specificity of magnesium sulfate is that the non-contracting uterus is not sensitive to this drug, so if there are no contractions, then the drug should not be prescribed. Foreign doctors, most of them, use this very principle, and besides, they do not use magnesium for more than two days, and in rare cases for more than 4 days.
The use of magnesium sulfate requires constant monitoring of laboratory parameters of electrolyte (salt) metabolism in the mother and her general condition, which, alas, is not practiced by many doctors.
Since no tocolytic drug has any advantages in prolonging pregnancy, after stopping the administration of magnesium, other tocolytics are not prescribed, including for the purpose of "prophylaxis".
If magnesia is preferred in the third trimester, then indomethacin more effective in the second trimester, mainly before 30 weeks of pregnancy. This drug belongs to the group of inhibitors of prostaglandin synthesis, or in other words, this drug inhibits the production of substances (prostaglandins) that play a role in the contraction of the muscles of the uterus. It is popular with non-pregnant women for treatment premenstrual syndrome and painful periods.
Indomethacin is also effective for polyhydramnios. However, this drug has a negative effect on the fetus, especially if it is used in the third trimester, so it is usually not prescribed after 32 weeks. In women, it can cause gastrointestinal bleeding, an allergic reaction and a blood clotting disorder. Headache and dizziness are also common. From the same group of drugs, naproxen, aspirin and a number of other drugs were occasionally used, but there is little information about their benefits in preventing premature birth.
Hormonal drug - progesterone, in its various forms, which is abused in early pregnancy, used certain period the time in pregnant women is between 24-32 weeks of gestation, but the results have been inconsistent. Most doctors do not use progesterone or its analogues during the second half of pregnancy.
TO nifedipine, which belongs to the group of calcium channel blockers and which is often used to treat hypertension and cardiovascular diseases, is treated with great caution, since it is a new drug in obstetrics. It also has many side effects, however, when used correctly, it is very effective in short term prolongation of pregnancy.
One of the new drugs that began to be used in obstetrics not so long ago is nitroglycerine... Nitroglycerin is known to many older people suffering from cardiovascular diseases, in particular angina pectoris or angina pectoris. The drug exists in different forms and for the prevention of preterm birth after invasive procedures (amniocentesis, cordocentesis, laser relief of placental vessels, etc.), as well as for the relief of preterm labor, it is used in the form of percutaneous patches, intravenous infusions or droppers, nasal sprays, tablets under the tongue. The effectiveness of nitroglycerin is still being studied in a number of countries by conducting large clinical trials. Like all tocolytics, nitroglycerin is prescribed only at 24-32 weeks, not earlier or later.
The indication for the appointment of nitroglycerin is the presence of at least 4 contractions within 20 minutes and the shortening of the cervix, that is, the criteria for setting preterm labor are taken into account. Also, this drug is not prescribed if another tocolytic drug has been prescribed to the woman before.
Preparations from the group of beta-sympathomimetics, which include terbutaline, ritodrin, and very well-known in the territory former countries Union Ginipral - not used in many countries due to serious side effects. The use of this group of drugs causes abnormalities in the mother's heart, and can also lead to cardiac arrhythmias, cardiac ischemia (pre-infarction and infarction) and pulmonary edema.
As numerous clinical researches, beta-sympathomimetics do not reduce the incidence of preterm birth, do not improve the outcome of pregnancy, do not reduce the incidence of newborns, do not improve the weight of newborns, and therefore should not be used by pregnant women, especially for the prevention of preterm birth. Many of these drugs have never been tested on pregnant women, although they are prescribed for the purpose of prolonging pregnancy, and the studies that have already been carried out are not enough to talk about the safety of beta-sympathomimetics for pregnant women and their offspring. For example, clinical studies of Ginipral regarding the prevention and management of preterm labor were carried out in the 1980s, and more recent publications are devoted to cases with serious side effects of hexoprenaline.
All beta mimetics affect carbohydrate metabolism, increasing blood sugar levels by almost 40%, which means increasing insulin production. In women with diabetes, blood sugar levels can rise even higher and lead to a loss of glucose control.
Very often, pregnant women are prescribed ginipral with or without additional medications, ostensibly for the prevention of premature birth, if, God forbid, the doctor does not like the "uterine hypertonicity". Unfortunately, few pregnant women read the instructions for use of the drugs they are taking.
If beta-mimetics, which include ginipral, do not improve the outcome of pregnancy and do not lower the rate of preterm birth, is it worth prescribing this drug, which also has many side effects? The answer logically suggests itself: of course, in this case - not worth it. And why is it prescribed to almost all pregnant women in a row? Primarily because of reinsurance.
Pregnant women, long before pregnancy, are tuned in by doctors to pregnancy complications and "terrible" threats of pregnancy loss. Thus, the woman is in constant fear of losing her pregnancy. First, she takes progesterone, then switches to ginipral - not a single day of pregnancy without a pill (I think that such a slogan can be hung during the course of most antenatal clinics). If, for some reason, a woman does not take the prescribed drugs, then in the event of termination and loss of pregnancy, she will reproach herself or she will be reproached for having lost her pregnancy due to her refusal to take medications.
Many women do not know and do not understand that the prescribed medications most often have nothing to do with maintaining pregnancy, or, on the contrary, can lead to termination of pregnancy if they are abused. Doctors also reinsure themselves so that later no one could reproach them that they did not do "everything possible" to preserve the pregnancy. The fact that the concept of "everything possible" has acquired big sizes in the number of dangerous and harmful drugs and procedures, no one analyzes, refutes or criticizes, since most work according to the principle "the more, the better, because what the hell is not kidding ..."
There is no need to be afraid of premature birth, although they are fraught with many negative consequences... But the mother's positive attitude, the absence of fear and panic act much more salutary than combinations of often unnecessary medications, on which a woman becomes psychologically dependent.
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