Drugs in this group have an inhibitory effect on the emetic center of the medulla oblongata. Suppression of the gag reflex can also be achieved by administering local anesthetics inside – novocaine, anestezin, which depress the sensitivity of the afferent part of the reflex arc – chemoreceptors of the gastric mucosa.
The main group of antiemetic agents either directly inhibits the emetic center, or acts indirectly, exerting an inhibitory effect on the chemoreceptors of the trigger (“trigger”) zone located at the bottom of the IV ventricle of the medulla. In the nucleus of the emetic center are receptors that are selectively sensitive to the action of acetylcholine and histamine. Anti-emetic effect has a means of inhibiting these receptors. Neuroleptics, diethylperazine (torekal), cetarazine, meterazine, propazine and others have a similar effect; antihistaminic drugs digithydrinate (dedalon), diprazin and others; combined anticholinergic agents – aeron and others; central D2-dopaminoreceptor blockers – metoclopramide (reglan, raglan), etc.
Antiemetics take one of the leading places in the arsenal of drugs used during pregnancy. Since antiemetics in a significant proportion of cases are used by pregnant women without a prescription, this creates additional prerequisites for studying their possible adverse effects on the fetus.
Some teratogenic effects have been experimentally established in certain drugs used as anti-emetic agents, and, in particular, anti-histamine drugs cyclizine and meclizine used abroad. Cyclizin, taken in doses that are 10–20 times higher than therapeutic, caused in the offspring of rats eye defects (cataracts, anophthalmia) and the nervous system (microcephaly). In rabbits, the teratogenic effect of cyclizin was even more pronounced. Spina bifida, encephalocele, microcephaly, no tail were observed. With the introduction of meclizine to white rats from the 10th to the 15th day of pregnancy, the offspring observed splitting of the sky, underdevelopment of the lower jaw, defects of the development of the ribs and vertebrae.
Data on the possibility of using these drugs in clinical practice are contradictory. J. L. Schelling (1987) recommends their use to prevent vomiting in pregnant women. According to K. R. Held (1981), J.N. Lewis, A.W. Weingold (1985), meclizine does not have a teratogenic effect on the human fetus. According to the data of W. G. Mc Bride (1969), 4.4% of children whose mothers used cyclizin during pregnancy had malformations of the upper jaw, which is significantly higher than in children of the control group. However, in children whose mothers during pregnancy complained of nausea and vomiting, but did not use drugs, the incidence of upper jaw malformations was 3.6%. The author believes that this malformation depends most likely on the presence of early toxicosis in pregnant women than on the administration of cyclisin. At the same time, the teratogenic effect observed in various species of rodents with the use of these preparations suggests antiemetic drugs of this series as potentially dangerous to humans. This is the basis for the exclusion of their use in the first trimester of pregnancy [K. Brendel, K. S. Duhamel, T. Shepard N. 1985].
Recently, metoclopramide (cerulacal) has been used as an antiemetic agent for the treatment of early toxicosis of pregnant women [Martynshin M. Ya., Arkhangelsky A. Ye, 1981]. M. Bylsma-Howell et al. (1983) investigated the concentration of metoclopramide in the blood of the mother and newborn in 23 women who had undergone a cesarean section, with which the drug was administered intravenously at an average dose of 0.14 mg / kg 15–51 minutes before the operation. Evaluation of newborns on the Apgar scale, neuropsychiatric symptoms, and functional status of the cardiovascular system corresponded to those in the newborns of the control group. According to J.N. Lewis, A.V. Weingold (1985), metoclopramide does not possess teratogenic activity against the human fetus. However, it should not be prescribed in conjunction with phenothiazine derivatives and other antipsychotics.
Abroad, bendictin, which is a combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), is widely used as an antiemetic used during pregnancy. The study of this drug was carried out on monkeys, which bendictin was administered orally on the 22-50th day of pregnancy in doses 10 times higher than the therapeutic dose for humans. Congenital defects of the mitral valve of the heart were revealed in a significant number of fetuses [Hendrickx A. G. et al, 1985]. According to G. T. Gilson et al. (1981), bendictin increases the frequency of defects of the reproductive system in children whose mothers used this drug during pregnancy, as well as the frequency of birth of children with cleft upper lip or palate [Golding J. V, Baldwin J. A, 1983]. However, the review of N. Tuchmann-Duplessis (1984) presents data indicating a low risk of developmental malformations in newborns whose mothers used bendictin in the first trimester of pregnancy.