Embryotoxic effect of medicines. Dioxins in boiled water and food - the effect on man and the effects of poisoning
(according to the book of Dr. O.A. Mazura "CapillaryTherapy Heals 95% of Diseases")
According to the data of modern domestic and foreign medical statistics, a significant number of women have at the time of pregnancy or transfer to various periods of extractive pathology, that is, diseases of the unpleasant sphere, directly related to childbearing bodies. According to the same data, up to 80% of women during this period, at least one pharmacological preparation takes. On average, according to foreign specialists, each pregnant woman takes 4 medicinal substances, not counting the vitamins and gland preparations.
It is well known that many drugs penetrate the fetoplacentage barrier and create real concentrations in the blood plasma of the developing fetus, which can negatively affect its development. The weakness of the function of eliminating (withdrawing toxins) organs of the future child can cause a fetotoxic (poisoning fruit) effect when applied even concern for an adult medication. Incorrectly prescribed treatment can spoil the whole person's lifeafter his birth.
Doctors prescribing pharmacological preparations for pregnant women, should know and take into account the following major moments:
- basic periods intrauterine development organism;
- embryotoxic (poisoning embryo), teratogenic (deformity) and fetotoxic effects of drugs;
- metabolism (transformation in the body) medicines in pregnant women;
- transition of medicines through the placenta and oil flooded water;
- metabolic features of a developing fetus;
- the main periods of intrauterine development and the impact of drugs for the future child.
As you know, the human body in the initial period of its development takes place three stages:
- Period of blasto- and embryogenesis;
- Period of fruit development;
- Newborn period.
Therefore, drugs used by a pregnant woman can cause three options for the body of the future child: embryotoxic, teratogenic and fetotoxic.
Embryotoxic action
Embryotoxic action occurs in the first three weeks after fertilization of the egg and lies in the negative effect of drugs on the zygota and blastocyst, which are in the lumen of phallopyan pipes or in the uterine cavity (before implanting the fruit eggs) and the umbilical secret. Damage and, as a rule, the death of blastocyst is caused by the following pharmacological substances: hormones (estrogens, progestogens, somatotropic hormone, deoxykorticosterone acetate), antimetabolic (mercaptopurin, fluorouracil, cytarabin, etc.), carbohydrate (iodacetate) and protein (actinomycin) exchange, Salicylates, barbiturates, sulfonamides, fluorine-containing substances, antimitotic drugs (colchicine, etc.), nicotine. If the germs of man continues to develop in the womb of the mother, therefore, it is not damaged.
Teratogenic action
The teratogenic action can develop from the third to the tenth of the week of pregnancy (but many experts rightly offer to extend the boundaries of the dangerous period before the 12th week of pregnancy) and leads to various violations of the normal development of the fetus, the emergence of the anomalies of its internal organs and systems. The variant of the defect depends on the period of pregnancy, on which organs are laid and intensively formed by the embryo during the reception of the drug. It is believed that the most dangerous period for the development of large defects, that is, for the manifestation of teratogenicity of the drug, is the 3-10th week of intrauterine development, which corresponds to about 5-12 weeks after the first day of the last menstruation. Consequently, teratogenic action is most likely shortly after implantation of an egg to the wall of the uterus, that is, when a woman often does not know that she is pregnant.
The probability of the development of vice in the embryo depends not only on the prescribed pregnant woman of the pharmacological drug, but also from its age (the probability increases, if a pregnant woman is 25 or older than 3 years), from the state of its health, the functioning of the elimination (derivation) of drugs, doses of drug, The duration of its purpose, genetic predisposition to the development of one or another vice.
By the degree of danger of the development of teratogenic effect, researchers share medicines into three groups.
To the 1st group of substances, randomly dangerous for developing fetus and therefore, absolutely contraindicated pregnant women include: Talidomide, antifolithic preparations (methotrexate, trimethopris, co-trimoxazole), androgens, diethylstilbstrol and hormonal oral contraceptives. Reception of the latter is recommended to stop at least 6 months before the planned pregnancy.
The 2nd group is somewhat less dangerous for the fetus of funds include drugs prescribed by suffering epilepsy, diabetes, malignant neoplasms, and some others. Chronically occurring diseases themselves are definitely a factor predisposing to the occurrence of teratogenic effect. However, the potential danger of the teratogenic effect of pharmacological funds of this group, to which belongs to: antiepileptic agents (diphenin, hexamidine, phenobarbital, valproic acid), alkylating antitumor drugs (EMBICHIN, DPANA, SARCOLIZIN, HLORBUTIN), oral (used inside) antidiabetic agents, as well as ethanol (ethyl alcohol) and progesterone.
The 3rd group includes drugs that cause malformations with predisposing to this conditions: I trimester of pregnancy, young or "elderly" age of pregnant women, high doses of the drug and so on. This group of medicines is: Salicylates, antibiotics of Levomycetin groups and Tetracycline, anti-tuberculosis, chinin, imizine, fluorotan (dangerous for pregnant women - workers of anesthesiological offices), vitamin K antagonists, mesprotan, neuroleptics, diuretic products, anaprilin.
Fethotoxic action
In the late pregnancy, the fetus organs are mostly formed, so pharmacological funds can no longer cause large anatomical defects. Damage can manifest itself in presence, damage to tissues, inhibited or disturbed function of any organ or disturbed behavioral reaction. The appointment of pregnant hormones, androgens or progestogennes is accompanied by the masculinization of the fetus. Iodides, lithium and anti-rampants used in large doses provoke the development of the goiter. Tetracyclines violate the development of teeth and bones; Hinolon violates the development of cartilage. Inhibitors of prostaglandinsintetase (acetylsalicylic acid and indomethacin) can slow down the occurrence of childbirth, and the fetal cause a violation of the function of the cardiovascular system, as the prostaglandins are involved in maintaining the patency of arterial flow in the fetus, relaxing its muscles.
Fethotoxic action occurs due to an excessively pronounced and characteristic of a given drug pharmacological impact on the fruit (more often in last weeks Pregnancy) or a specific drug-specific effect. For example, the appointment of Indomethacin a pregnant woman leads to the closure of arterial duct at its fetus before the occurrence of childbirth; Beta adrenomimetics violate the fruit carbohydrate exchange; Aminoglycosidic antibiotics have a nonotoxic effect on the fruit, that is, the fabrics and the functions of the inner ear are affected. Clinical experience shows that the appointment of some drugs to pregnant women can lead to the development of perinatal (related) pathology and even the death of the fetus or newborn baby.
Medicines before childbirth
Medicinal preparations used on the eve of delivery can cause negative pharmacological effects in postnatal (postpartum) period. For example, the difficulty of breathing through the nose, drowsiness, difficulty feeding the child is manifested when using reserpine. Levomycetin antibiotic causes newborns vascular collapse and bleeding violations, since they do not conjugate. Vasodinating agents provoke a decrease in the blood supply to the uterus and the fetus. When using beta-blockers may be lacking the reaction of the fetus for hypoxia. Sulfanilamide drugs displace bilirubin from its connection with plasma proteins, as a result, the child is born with jaundice. Anticoagulants and antiagregants increase the risk of bleeding. In children born by a woman with addiction to opioid drugs, the abolition syndrome with manifestations of physical nature can develop.
In children whose mothers took psychotropic drugs during pregnancy, there are changes from the psyche due to the slowdown in the development of the central nervous system. In particular, such children may later be difficult for learning.
Lack of profound research covering a large number of drugs, do not allow clear recommendations to increase or decrease doses, so most pregnant drugs are introduced in conventional therapeutic doses.
Drugs can fall into the body of the fetus through the placenta (transplacental path) and amniotic fluid (spicy water), which it actively absorbs through its tracheobronchial tree and lungs, as well as through the gastrointestinal tract. For most pharmacological preparations, their accumulation in amniotic fluid is small, but some create significant concentrations, such as ampicillin antibiotics and oxacillin. This property is used in the treatment of intrauterine fetal infections.
Features of the metabolism of the fetus
An important role in the processes of metabolism (biochemical transformation) of drugs plays the function of the liver, which in the fetus is immature both in functional and morphological terms. Functional maturation of the liver in the fetus and the appearance of enzymes, metabolizing drugs in it, occurs in parallel with histological (tissue) maturation until the moment of its birth. However, full-fledged metabolism is possible only in the process of postpartum development. Insufficient inactivation of drugs of fetal liver leads to the fact that a number of drugs (barbiturates, narcotic analgesics, indirect action anticoagulants and many others) have a more pronounced toxic effect on the fruit than on the maternal organism.
Embryotoxic action. This ability of the studied substance is adversely acting into developing embryos. In medical toxicology, embryotoxic effects are studying on females of white rats, which are injected through a probe throughout the probe or give the drug. On the 17-19th day of pregnancy, the beginning of which is established according to the results of the study of vaginal smears, rats are killed, calculate the number of fruit and yellow bodies in the ovaries, living and dead fruits. Comparing the results of these studies in the experimental and control groups, establish the degree of embryotoxic activity of the drug. Part of pregnant rats from experienced groups are left for childbirth, while take into account the duration of pregnancy, the number of fruits, their mass, the length of the trunk of newborns, is the development of their development (increase in length and mass for a certain period, the opening time of the eye, coating of the hair, the start of independent movement on the cell and eating feed). In addition, the survival rate is rats, the distribution of them on the floor. At the same time note: selective embryotoxicity - the effect is manifested in doses, not toxic for the parent organism; General embryotoxicity - manifests itself simultaneously with the development of intoxication of the body of the mother; Lack of embryotoxicity - the effect is not observed in the signs of intoxication of the maternal organism (Bear, 1968).
There are no methodological approaches to the definition of the embryotoxic properties of veterinary drugs.
I La first stages, apparently, it is advisable as a model to use white rats as a model, since experiments on farm animals are difficult because of the lengthy time of pregnancy and a relatively small number of individuals in litter (with the exception of pigs). In the event that it is established that the studied compounds have a common or electoral embryotoxicity, put experiments on animals, and above all on pigs. Preparations, depending on their intended purpose and the method of use, it is advisable to give with food, introduce intramuscularly or applied.
Teratogenic action. This is an action in which the formation of the fetus is disturbed during its embryonic development. It manifests itself in the form of deformities. Teratology as science has developed after cases with thalidomide - a drug, widely used by pregnant women in Western Europe as a sleeping pills and sedative. As a result, the birth of children with congenital defects was recorded.
In medical toxicology, the teratogenic effect of pesticides is determined on white rats. For this, the drug animals are injected inward after 1 day throughout the pregnancy. Part of the animals of experienced groups are killed on the 17-20th day of pregnancy, the part is left to childbirth. In the opening of the killed rats, the average number of yellow bodies per female, normally and abnormally developing embryos, as well as resorboated fruits.
Natural childbirth, the number of births of females, who was arranged offices, including stillborn, establish an average weight of the offspring, the length of the body, limbs and other morphological features (Bear, 1969).
The teratogenic effect of drugs on agricultural animals is not studied.
Under the manifestation of the teratogenic effect, the following deformities are possible: the absence of a brain (anencephalia); underdevelopment of the brain (microcephaly); Increased cerebrospinal fluid content in brain ventricles (hydrocephalus); Brain hernia (Encephancelium); splitting the first arms of the vertebrae (bifid spin). In addition, abnormalities in other organs are possible: no eyes (anofthalmia); the presence of one eye (cyclopia); Hare Lip; cleft palate; lack of limbs (peramial); lack of tail; Shortening of the tail and others.
Gonadotoxic action. When studying gonadotoxic action, the effect of the studied drug is set separately to the sexual sphere of females and males. Experiments are carried out on white rats. On the females, the effect of the drug on the astral cycle and the ovogenesis, on the male - on mobility, morphology, the cut-wall, sperm and spermatogenesis are investigated.
Estral cycle is determined by exploring vaginal strokes. For this, a heated physiological solution (2-3 drops) was introduced in the vagina, they passed it several times through a pipette, and then introduced back to the vagina. After this procedure, with the help of slide glasses, strokes from the vagina are prepared, they fix them above the flame and stained for 1 min with 1% aqueous solution of methylene blue. The smear is viewed under a microscope with a small magnification.
Distinguish the following main steps of the estral cycle:
Phase of Proetrus (forerunters) lasts several hours and is characterized by a predominance in the smears of epithelial cells;
Phase Estrus (Tekka) lasts 1-2 days. In this stage, buried polygonal cells (scales) are mainly present;
Metastreus (Fixch) has a duration of 1-2 days and is characterized by the presence along with the scales of epithelial cells and leukocytes;
The phase of diestrus (phase of rest between the flows) is characterized by the presence of leukocytes and mucus. The duration of this phase is equal to half of the entire cycle.
Changes in the duration of the steps of the estral cycle or the nature of the cells at different stages is an indicator of the test substance.
To study the action of a chemical on evogenesis prepare histological sections from ovaries and determine the stages of the development of follicles in experienced and control groups of animals.
When studying the gonadotoxic effects on males, the ratio of moving and fixed forms of sperm, the presence of pathological forms, their resistance and spermatogenesis phases (Bear, 1969) are determined.
Mutagenic action. Some chemicals violate the transmission of genetic information, as a result of which mutants are possible - individuals with signs that are not peculiar to this type. Therefore, the study of mutagenic properties of pesticides and other chemicals is one of the necessary stages of toxicological research. In a number of countries, a screening test is used for this purpose - the Ames Test. As a test organism, separate bacteria strains of the Salmonella group, highly sensitive to chemical mutants are used. In the presence of potential mutaging in the studied chemical, genes are cleavage of genes and the number of colonies on a dense nutrient medium increases sharply. However, the mutagenity of a chemical substance identified using this test cannot be recognized as absolute, since higher animals have powerful protective systems that protect cells responsible for transmitting genetic information from the effects of external factors, including chemicals. In many cases, under the influence of enzyme systems, the chemical may be detoxified before it reaches the "target".
Even on the topic of embryotoxic, gonadotoxic, teratogenic and mutagenic effect of toxic substances:
- Unwanted effect of medicinal substances. Side effects of allergic and non-allergic nature. Cancellation syndrome. Toxic effects of drugs. Embryotoxicity. Teratogenicity. Mutagenicity. Carcinogenicity.
- To the question of using a microer test for assessing the mutagenic action of the early period of opisthorchoic invasion on mice
- Poisonous (toxic) substances and their classification
- Methods for determining toxic substances in environmental facilities, animal tissues and animal products
Many medicinal substances appointed during pregnancy pass through a placental barrier and come to the fetus.
There are several options for the transition of chemicals through the placenta: ultrafiltration, simple and lightweight diffusion, active transport and others. Ultrafiltration processes, dependent on the magnitude of the molecular weight of the chemical, take place in cases where the molecular weight of the substance does not exceed 100 D. Most of the medicinal substances used in obstetrics have a large mass, and for them, a similar mechanism is inactive. But many drugs have a molecular weight of 250-500 d and penetrate the placenta quite easily. The diffusion process means the transition of a substance from the region of greater concentration to the area of \u200b\u200bless. With the help of such a mechanism, the transplacent transition of most lipotropic drugs is carried out. Lightweight diffusion differs from the simple in the way that the transfer of chemical compounds through the placental membrane along the concentration gradient is carried out by special carriers (proteins of enzymes) with a greater speed than is possible with a simple diffusion. In this way, for example, amino acids are carried out. With the active transport of medicinal substances through the placenta, they are transferred to special carriers. These processes are conjugate with the enzymatic activity of the placenta and are carried out with energy consideration.
Placenta, including early, is a metabolically active body with enzyme systems. It contains enzymes capable of playing a certain role in the intensity of the transfer of certain groups of drugs through the placenta and catalyze the biotransformation of drugs. Therefore, the placenta serves as a kind of destination biochemical protection against exogenous substances before they fall into the blood flow of the fetus. For the transfer of chemicals, the thickness of the placental membrane is maintained: at the beginning of pregnancy, it has a relatively large thickness (25 microns), and in the last trimester of pregnancy, the thickness of the epithelial layer of the trophoblast sharply decreases to 2 μm by the time of delivery, which largely facilitates the passage of drugs. Various diseases, including diabetes mellitus, gestosis, significantly affect the permeability of the placental membrane.
A significant effect on the transplacental transition is provided by the ability of the drug to contact blood proteins. The higher the ability of it to such binding, the slower it penetrates through the placenta.
Until the end of the 70s, there was a delusion that the drug that does not penetrate the placenta to the fetus is harmless and can be widely used for ante and intranatal therapy. In 1969, the results of experimental studies of IP were published. Romanygina, which established that the introduction of pregnant females of the rats of oxytocin and having wishally worsens a number of fetal life indicators, while the receipt of these drugs directly to intrauterine fruits does not cause changes in their state. The author believed that this circumstance could be explained by the negative influence of these drugs on the placenta. The studies conducted bioenergy studies confirmed the oppression of the respiratory processes and oxidative phosphorylation in the mitochondria of the placenta under the influence of intravenous administration of oxytocin. His subcutaneous introduction was less harmful. Practically did not cause bioenergy changes to stimulate generic activities by intravenous administration of oxytocin on the background of serotonin, which can be explained by the electoal properties of the latter and stimulation of adaptation reactions through cyclase systems.
Significantly worsens the bioenergy of the fruit of the preyone (Vyadlil), applied to the aim of painting. At the same time, the use of sodium oxybat (sodium oxybutirate) for anesthesia, not only does not lead to disorders of oxidizing agent processes in placenta mitochondria, but even somewhat stimulates their respiratory activity.
It should be borne in mind that, in addition to the transplacental exchange of drugs, the paraplacementary transition is also possible.
The fetus organs, especially the gastrointestinal tract, are directly related to the amniotic cavity and fluid filling it, so the drugs present in it are easily absorbed by the fruit.
Intestinal and kidneys are involved in excretion. These methods of transport of substances include not only the blood of the mother and the fetus, but also the oily water and the urine of the fetus.
According to the fetus, drugs are divided into three main groups:
- not penetrating through the placenta and, therefore, do not directly affect the fetus;
- carrying out a transplacental transition and affecting the fetus;
- passing through the placenta and accumulating in the body of the fetus.
It should be noted that for substances capable of penetrating through the placenta, there is no proportional dependence of toxicity on the degree of penetration.
Substances with toxic effect can be classified by their ability to cause non-specific and specific toxic effects in the fetus.
Non-specific reactions can be induced by most drugs in case of exceeding their dosage.
Substances showing a specific effect affect the development of the fetus, regardless of whether they have a toxic effect on the maternal organism or not.
The specific toxic effect of drugs may be the character of the embryotoxic, fetotoxic and teratogenic effect.
Embryotoxic effect is especially manifested in the first three weeks of pregnancy due to the influence of the drug on the zygota and blastocyst. Some antibiotics, as well as hormones (such as estrogens), cytostatic, barbiturates, sulfonamide preparations have a similar action.
The fetotoxic effect of pharmacological preparations is manifested in the overall strong toxic effect on the fruit or the occurrence of a particular specific side effect. The fetotoxic effect of drugs can be expressed as structural and functional deviations. So, for example, Indomethacin, like most NSAIDs received by pregnant in the first trimester leads to the SIR.
The teratogenic effect is the property of the physical, chemical or biological factor, in particular the drug, cause imbounds of embryogenesis processes, leading to the emergence of developmental anomalies.
The nature of the vice is determined by the term of gestation. Chemicals can significantly affect the development of organs during their intensive formation. Some authors allocate the "classic teratogenic period", during which the largest teratogenic effect of substances is noted. This is due to the fact that a certain impairment of morphogenesis corresponds to the action of a particular substance on organichane during the period of their intensive formation. The duration of the "classic teratogenic period" - 31-71 days from the last menstruation (5-10 weeks of gestation), which corresponds to the beginning of the formation of the main organs and tissues (from the heart and the central nervous system to neba and ear shells).
The effect of some chemicals can be slowed down, delayed, possibly the presence of a latent period, which is listed: from the effects of matter on the fetus before its effect is detected. Diethylstilbastrol is a classic example of slow motion. From 1940 to 1971, 6,000,000 mothers and their children were exposed to this estrogen, which was appointed for the treatment of non-obscure and premature birth. In women whose mothers received diethylstilbastrol, the risk of developing the adenocarcinoma of the cervical and vagina increases (a very rare shape of cancer in women under 50 years old), and men have diseases of the reproductive sphere.
It should be borne in mind that the teratogenic action can not have not only preparations that a woman gets during pregnancy. Some of them used before conception cause malformations of the fetus. For example, retinoids - teratogens with a long latent period, may affect the development of the fetus, even if the course of their application is completed before conception.
The reception of drugs by the father affects gametogenesis and can cause malformations of the fetus. These drugs include drugs for anesthesia, antiepileptic drugs, diazepams, spirironolactone, cimetidine.
For example, the reception of diazepama father increases the likelihood of upper Lip. and / or solid neba at the future child. In sperm of men receiving anti-epileptic agents, especially phenytoin, morphologically changed and low-voltage spermatozoa are found.
The term "teratogenicity" some authors use quite widely. They contribute into this concept all deviations from the norm during the development process from the moment of fertilization to childbirth: death, deformity, developmental delay, functional failure.
Some authors allocate "behavioral teratogenicity." It lies in violation of behavior, intellect, memory in a postnatal life in a person who was subjected to perinatal (or neonatal) exposure to xenobiotics, including drugs. A person has reliably established a negative impact on the behavior of the offspring of ethanol, a number of narcotic analgesics, phenytoin, genital hormones. In animal experiments, a significant range of pharmacological agents was revealed, the impact of which violates the behavior in postnatal life. These substances include chlorpromazine, haloperidol, phenytoin, corticosteroids, germ hormones, retinol, cytostatics. These substances violate the production of conditional reflexes, lead to explosive outbreaks of hyperactivity, violations of social behavior.
The most reliable information about the presence of risk of use of a drug give direct clinical observations. However, these data are small. Clinical observations should be preceded by experimental study of the properties of the pharmacological preparation in experiments on laboratory animals.
The primary basis for the use of animals in biological experimental systems is the fact that the well-known main chemical drugs, teratogenic for humans, are most often teratogenic for animals. But the reverse relationship is not always noted, and the substance, harmless to animals, is not always safe for humans. This is due to interspecific differences, which are due to the difference in the inner sensitivity of embryonic and fetal processes to the penetration of chemicals, the rate of embryogenesis, the peculiarities of pharmacokinetic factors.
Although almost 1000 chemicals that have the teratogenic effect on animals are known, the teratogenic effect of only several chemicals affecting a person is proved. These include: alcohol, chemotherapeutic drugs (antimetabolites, alkylating agents), anticonvulsants (trimetadion, valproic acid, phenyotoin, carbamazepine), androgens, warfarin, danazole, diethyl stystrol, lithium, retinoid, talidomide.
In 1991, the WHO International Commission for Control for the Use of Medicines during pregnancy began to work. According to her, 86% of the observed women took medications, while obtaining an average of 2.9 drugs (from 1 to 15) appointed by the doctor.
According to V.V. Abramchenko (1994), 80-90% of women during pregnancy take medications, 40-60% use them in the first trimester of pregnancy, 25% take their long time.
Most doctors of the whole world decided to stop the uncontrolled use of drugs during pregnancy. State programs that control the use of drugs are being implemented.
One of the steps to organize safe treatment during pregnancy was the mandatory introduction of special labeling of medicines. Markings contain information on the degree of risk of drug use during pregnancy and level of research proving its safety. For example, classifications entered by the Australian Cate- ORISATION OF RISK OF DRUP USE IN PRE-NANCY) and US Power Management and Medications (FDA - US Food and Dru-Administration), very similar and contain 5 main categories:
· Category A - The drug that was used by a large number of pregnant women (including under control studies) and women of childbearing age, while there are no reasonable data that it led to an increase in the frequency of fetal defects, was not detected direct or indirect side Effects on the fruit (example: folic acid, levothyroxine sodium).
· Category B - the study of the drug on animals proved the safety of the drug, but there is no clinical trial data, or when studying animals, side effects are revealed, which were not confirmed by clinical trials (example: amoxicillin).
· Category C - the drug, which, as a result of the pharmacological effect, causes (or may cause) adverse side effects, but does not cause malformations (side effects can be reversible), or animal research has proven the danger of the drug, but the clinical trials were not conducted. This category should be prescribed only in cases where the benefits of its use exceeds the potential risk to the fetus (example: nifedipine, omeprazole).
· Category D - the drug, which, as a result of the pharmacological effect, causes (or may cause) irreversible adverse side effects, malformations. Or studies have proven the danger of the drug for people, but despite this, it is possible to use the drug according to life indications, when more secure drugs are ineffective (example: phenytoin, propylthio-oscil).
The drug is contraindicated in pregnant women and women who have pregnancy can come (example: warfarin, talidomide).
The appendix presents data on the safety of the use of various groups of medicines and the effects of them on the fruit.
Effect on the fruit of individual groups of drugs taken during pregnancy
The most consumable means include central neurotropic hypotensive means of methyldop and clonidine (Category B). The mechanism of their action is not entirely common: they provide a partial central aagonistic effect and at the same time slow down the sympathetic activity at the level of pregganionic sympathetic endings. Due to the fact that against the background of these drugs, sodium and water excretion decreases, it is advisable to combine their appointment with diuretics. It should be borne in mind that at high dosages the fruit is able to cumulate drugs, which can reduce the excitability of its CNS, cause a depressive state.
The development of autoimmune hemolytic anemia, lesion of the liver with long-term use of drugs can be a dangerous complication.
Ganglioblocators. Hexametonia benzosulfonate (benzenexonium), Azametonia Bromide (Pentamine) and other drugs are less and less used in obstetrics. Care of their use is due to the possible deterioration in the pancakeholders. Cases of fetal death due to hypoxia are described.
Sympatholites. The reserpine and other similar drugs violate the excitation transmission at the level of the presynaptic adrenergic fiber membrane. With prolonged use, it is possible to exhaust catecholamines in the brain, which leads to the oppression of the CNS of the fetus, drowsiness, depression of the newborn. May cause delay in the development of the fetus. During pregnancy, it is necessary to apply with great care.
badrenoblocators. Propranolol, atenolol, metoprolol (Category C), possessing structural similarity with endogenic catecholamines, are associated with postsynaptic membrane receptors. It should be avoided by their use in the first trimester and a few days before delivery due to possible side effects. Preparations of this group cause a decrease in the renal blood flow and the fall in glomerular filtering. Removing the inhibitory effect of adrenomimetics, drugs can lead to premature gods, worsen the fallower blood circulation, which is fraught with the delay in the development of the fetus. The action on the fruit is manifested in the development of bradycardia, hypoglycemia, jaundice, the oppression of the breath of the newborn.
Vasodilators. Value, arterilation and mixed vasodilators distinguish. Typical venous vasodilators include nitroglycerin. It reduces blood pressure, improves fetoplacentar blood circulation.
It is believed that it does not reduce the blood pressure of the fetus. However, the drug is attributed to the C category, and its application is recommended only during childbirth. Hydralazine (Category C) - Arterilar Vasodilator. Women can cause tachycardia, angina, violation of the GTS functions, accompanied by vomiting.
Diazoxide is a thiazidine derivative with vasodilatory action. The drug, passing through the placenta, inhibits the secretion of insulin fruit, which can lead to long hyperglycemia.
Calcium channel blockers prevent the input of calcium ions into a cell through potential-dependent cytoplasmic membrane channels. As a result of this substance of this group, there is a relaxing effect on the vessels, the gastrointestinal tract, the urinary paths, the uterus. The following chemical groups of calcium channel blockers are distinguished:
· Phenylaclamines: Verapamil;
· Benzodiazepines: diltiaze;
· Digidropyridines: nifedipine, nipple, nimodipine, isradipine;
· Diphenylpiperazines: zinnarizin, laidoflazine;
· Tetralin derivatives: Mibeffradin.
There is experience in using these drugs during pregnancy in hypertensive states, premature childbirth, with an asymmetric form of fetal growth delay. However, the use of these drugs should be treated extremely careful. Their action on the fetus is not studied enough. Most of the drugs of this group are classified by C. The negative effect on the fruit is known to the use of large dosages, which is expressed in the deterioration of the uterine blood flow.
Inhibitors of an angiotensin gluttering enzyme prevent angiotensin I in angiotensin II, which causes vasospasm, contributes to the release of aldosterone. Preparations of this group (captopril, saralazine) are contraindicated throughout the pregnancy, since their admission leads to a delay in the development of the fetus, lowland, the defeat of the fetal kidneys.
Medicinal plants have antihypertensive activity: the hawthorn flowers, herd grass, herb grass, daisy flowers, cumin seeds, valerian root, white mistletoe grass. They must be applied in the form of fees. There are biologically active additives (BAA), normalizing blood pressure. These include: Circulin, Hawthorn, Hypotenzine Plus.
Diuretics. Digestive means are called substances that cause an increase in the removal of urine from the body and reduce the content of fluid in tissues and serous cavities.
The appointment of diuretics is necessary for strict indications, especially in gestosis. It is necessary to be guided by the severity of disorders of the concentration and excretory function of the kidneys, the presence of symptoms of overload of the right heart departments. Apply drugs of all three groups, but it should be remembered that the derivatives of spiroranolactone (category C) are contraindicated with the initial renal failureThe application is not recommended to 12 weeks of pregnancy. TRIMENTEN (CATEGORY C) should be assigned only by strict indications.
Long-term therapy with thiazid diuretics can lead to significant violations of the electrolyte balance in the mother and the fetus. Hydrochlorostiazide (category D) is contraindicated in pregnancy. The use of saluretics before childbirth may cause hyperbilirubinemia in a newborn. Some authors recommend avoiding the appointment of furosemide (category C) during pregnancy. The smaller the period of gestation, the more pronounced the Furosemide delay in the fetus. The long-term consequences of the use of furosemide, which acts as behavioral teratogen, causing increased irritability and excitability of children has been discovered.
It must be borne in mind that, according to several controlled studies, the use of diuretics during the hestosis not only does not improve remote results, but may also worsen the forecast of childbirth.
Attention should be paid to a large spectrum of plant diuretics, the toxic effect of which is much less pronounced. Diuretic properties possess lingonberry leaves, scamphon of stincher, tocheries, flower vasil blue. During the eats of pregnant women, the use of fees containing also birch leaves and kidneys, licorice root, lingonberry berries, grass horsetail grass, the leaf leaves are triumphant, crushed rosehip fruits. It is possible to use dietary supplements.
Anti-inflammatory drugs. The most common group of this direction is non-steroidal anti-inflammatory funds (NSAIDs). This group of drugs has analgesic and antipyretic properties simultaneously with particularly pronounced anti-inflammatory activity. The drugs of this group include a number of phenylpropionic derivatives, phenyloxus acids [ibuprofen, diclofenac (C category B)], compounds containing an indole group (indomethacin (C category C)), pyrazolone bands [phenylbutazone (category C)]. Often, these drugs are used in self-medication at different times of pregnancy, without giving themselves the report in what consequences will entail it. Preparations of this group, with a rare exception, are contraindicated in the third trimester of pregnancy (transition to category D) due to the danger of premature closure of arterial duct. In the coming hours after administration, drugs of this group lead to a decrease in the pulsation indicators of the vessels of the fetus. In early pregnancy, it is also necessary to avoid the reception of the NSAID, as they have an embryotoxic effect, they can lead to the left ventricle hypoplasia, the defects of the interventricular partition. Acetylsalicylic acid can be considered the safest means of this group. There are results of controlled studies that make it possible to consider aspirin (in small doses - up to 100 mg / day) insole in the II and III of the trimesters of pregnancy. Previously, it was believed that the admission of aspirin leads to the internal hemorrhages of the fetus, but at present this fact does not find confirmation in scientific research.
A multicenter randomized slave-controlled study (CLASP) on the prophylactic use of small doses of aspirin (60 mg) in pregnant groups of high risk of developing obstetric and perinatal pathology with a burdened obstetric and somatic history showed that the long-term appointment of small doses of aspirin, starting from the second half of pregnancy, not It has influenced the frequency of the development of gestosis and gestational hypertension, but contributed to a decrease in the frequency of heavy forms of these complications, a clear trend towards prolongation of pregnancy, a decrease in the frequency of premature birth and the birth of small children was noted. The experience of using acetylsalicylic acid microodosis has accumulated in patients with a threat of early spontaneous miscarriageas well as with extragenital diseases, starting with early gestation periods. The inclusion in a complex of preventive and therapeutic measures The primary mon Microindosis aspirin contributed to the improvement of blood flow in microsudes, correction of tissue hypoxia and the suppression of apoptosis. Despite the absence of a reduction in the frequency of the development of gestosis in women with a burdened current pregnancy, they celebrated a reliable reduction in their severity against the background of Microidosis of Aspirin from the early period of gestation. In small doses, acetylsalicylic acid affects the ratio of prostacyclin / thromboxane, selectively inhibits the synthesis of thromboxane, thus affecting the aggregation properties of blood and microcirculation. Acetylsalicylic acid blocks the cyclooxygenase of endothelial cells, in which prostacycline is synthesized, the membrane-stabilizing effects of aspirin are also described.
In recent years, the specialists have increasingly sent to new group NPBS - selective cyclooxygenase inhibitors2. These include: celecoxib, valdecoxib, refekoxib. Their advantages, compared to classical NSAIDs, are significantly less toxicity, less influence on the fruit, high efficiency. For example, in 2002, a controlled study was conducted, in which the safety of the use of a selective cyclooxygenase cycloxygenase inhibitor2 celecoxib and indomethacin (non-selective NSAID) was carried out. Scientists concluded that the celecoxib is significantly safer than indomethacin. There is a suggestion that selective NSAIDs can be used to treat premature genera, In vitro studies confirm their pronounced tocolic activity.
It must be borne in mind that there are medicinal plants and dietary supplements with anti-inflammatory properties. For example, an evening primrose oil makes pain and relieves inflammation, reassuringly affects the nervous system. Its preparations are recommended for acute and especially chronic, long-term inflammatory processes, exacerbating during pregnancy, including diseases transmitted by sexually, respiratory and urinary organs. In the perinatal aspect, their long-term use in combination with antioxidants (vitamin E as the sum of the tocopherols) during placental insufficiency, due to or combined with chronic infection, as well as long-term intoxication is promoted.
Glucocorticoids. The systemic use of glucocorticoids is safe only in the case of adrenal insufficiency in the mother, when dosages close to the physiological one are used. Glucocorticoids are related to category C, that is, for their purpose, good reasons are needed (systemic diseases of the connective tissue, Hormone-dependent bronchial asthma). Sometimes the therapeutic effect of these drugs among the mother is more taken into account than the risk of fetal disextemogenesis. But it should be remembered that the long-term reception of prednisolone and other glucocorticoids, in addition to the abnormal tissue anomaly, can lead to a delay in the development of the fetus. With prolonged use of prednisone (category B) in the last trimester of pregnancy, the newborn can be observed hypoglycemia, adrenal crises. Cases of stillbirth during the reception of a woman cortisol throughout the pregnancy (on autopsy atrophy of adrenal cortex) are described. For the prevention of hyaline membranes, glucocorticoids are prescribed shortly before delivery. The maximum effect is achieved in children born more than 24 hours and less than 7 days after the start of treatment. Glucocorticoids reduce not only the risk of developing respiratory diseases, but also some other forms of neonatal pathology. Thus, the risk of intraventricular hematomas is halucing after the use of corticosteroids.
The positive effect is also noted in the case of necrotic enterocolitis. Phitogormons, in particular licorice root, have a corticosteroid-like, immunomodulatory, anti-inflammatory effect, they can be used for premonish preparation during pregnancy, allowing you to reduce the dose of appointed corticosteroids.
Antihistamines. Histamine plays an important role in the development of the fetus. It easily passes the placental barrier, provides normal conditions for implantation and development of the embryo, as it helps to transform the endometrium stroma cells into decidual tissue. Effecting the permeability of membranes, it regulates the exchange processes between the mother and the fruit, organogenesis. Therefore, to the appointment of antihistamine drugs during pregnancy should be treated with extreme caution. In the literature there is data on the teratogenicity of antihistamine drugs. Meclizin and cyclizin can cause the fetal stenosis of the gatekeeper, Sindactilia, the atresia of the anal opening, the hypoplasia of the lung, bladder, kidneys, hydrocephalus. The application of them in early pregnancy caused fruit resorption. It is proved that the incidence of anomalies is 5% (against 1.5% in the population). Reception of the dyphenhydramine's mother shortly before delivery can lead to the emergence of the child of generalized tremor, diarrhea several hours after birth (manifestation of intoxication by dipherrol).
If the mother has long taken DMEDDrol, a newborn may have abstineent syndrome, manifested by anxiety, increased excitability, convulsions.
Antidiabetic agents. It is difficult to establish a harmful effect on the fruit of antidiabetic drugs, as diabetes mellitus itself can lead to anomalies for the development of the fetus.
Insulin (Category B) has a large molecular weight and almost does not penetrate the placental barrier, therefore it has a minimal effect on the fetus. During pregnancy, women suffering from diabetes should apply insulin. Recently, information about the possible insulin ability to increase the likelihood of heart defects in children has appeared. Information requires deep research.
When using sulfanimide hypoglycemic drugs, there is a high level of perinatal mortality, when using chlorpropamide (category D) - 63%, tolbatamide (category D) - 23%. There is a violation of the implantation process, fruit resorption, a growth stop, in 6-13% of cases, detect anomalies of development (microfthalm, anofthalmia, cataract, Ancenophalia). The use of these drugs during pregnancy is contraindicated. It should also be abandoned by glyibenklamide, glypizid, metformin, repaglinide.
To achieve the main goal in solving the actual problem "Diabetes and Pregnancy" - Normoglycemia - with a decrease in insulin reception and sulfonamide derivatives, you can with the help of plant preparations (bean sesters, blueberry leaves, chopped root of burdock, cutting straw oats, flax seeds, leaves of dwarm nettle, leaves Birch, dandelion root, Hypericum herbs, strawberry leaves, High lunk root, horseways horsetail, rose hips, grass, grass, nine roots, daisy flowers, peppermint leaves).
Heart glycosides. They easily penetrate through a placental barrier. When they are used, the identical concentration of the substance in the plasma of the mother and the fetus is established. However, there is an opinion that the fruit has increased resistance to cardiac glycosides. Some authors argue that in the first trimester of pregnancy, the fruit is subject to the pronounced influence of digitoxine and digoxin (Category B), which leads to bradycardia.
Data on teratogenic action of cardiac glycosides is not received.
Anticoagulants. Due to the fact that during pregnancy, conditions are often created for the occurrence of thrombosis, the question of the use of anticoagulants is relevant. For a long time, the selection during pregnancy was heparin sodium (category B). By virtue of its high molecular weight, it almost does not pass a placental barrier and, therefore, does not directly affect the fruit. The drug can be applied at any gestation period. However, there are certain inconvenience of its use: the need to control the blood coagulation time with long-term administration, the possibility of thrombocytopenia. Therefore, some authors offer to use low-volume heparin, which is deprived of the disadvantages of heparin.
As a prophylactic agent in the II and III trimester of pregnancy, the use of small doses of acetylsalicylic acid is possible.
For the prevention of thrombotic complications, blueberry extract is recommended. It contains more than 15 different anthocianosides, which improve the functioning of cell membranes, prevent the blood cell aggregation, preventing the formation of blood clots, the destruction of collagen, the strengtheing wall of the blood vessels.
Blueberry extract also has antioxidant properties, which makes it possible to use both of these effects with violations of the tone of vessels and hypoxia.
Anti-infectious means. Most anti-infectious drugs adversely affect the fetus, so only the limited number is used during pregnancy. In the case of this group of drugs, it is necessary to especially carefully consider the benefit ratio for the mother and risk for the fetus.
Antibiotics. The most safe for the fetal antibiotics of the penicillin group (benzylpenicillin, ampicillin, oxacillin, dyloxicillin, amoxicillin) and groups of cephalosporins (cefalexin, cephalotin, cefaloridine).
Benzylpenicillin (Category B) is easily penetrating through the placenta (25-75%). From the blood of the fetus, the substance quickly enters the tissue. According to experimental studies and clinical observations, Penicillin is safe for the fetus. However, experimental studies on animals, which showed an embryotoxic effect with the joint use of penicillin and sulfonamides (the deformation of the limbs, the gap of the anterior abdominal wall, microftralmia, hydronephrosis) is noted.
The feature of ampicillin (Category B) is its ability to accumulate in amniotic fluid (against the background of a decrease in its concentration in the blood of the fetus). Therefore, it is advisable to therapeutic use of ampicillin with chorioamnion. The drug does not have a teratogenic or embryotoxic effect.
Cephalosporins (Category B) are different in pharmacological properties. Cephalotin and cefaloridine quickly pass through the placenta (up to 100%), cephalexin to a lesser extent (40%). Preparations can be used in the treatment of fetal infection. Cefalosporins can lead to hypoprothrombinemia due to reduced vitamin K metment, which represents the risk of bleeding.
The imipenem is a Blataman antibiotic. Widely used, does not possess fetotoxic and teratogenic effect.
Erythromycin (Category B) - Macrolid. It is considered a relatively harmless antibiotic. It has a low degree of penetration through the placenta (10-12%). However, it should be borne in mind that erythromycin is able to accumulate in the liver of the fetus, has hepatotoxicity. The exception is erythromycin Estolat (category X), which due to hepatotoxicity is contraindicated during pregnancy.
Levomycetins are slowly removed from the body of the fetus, they have teratogenic, embryotoxic effect. In animal experiments under the influence of chloramphenicol (leftomycetin), anofalmia, hydronephrosis, as well as a decrease in body weight, was noted. The use of Levomycetin during pregnancy is dangerous due to the possibility of developing a "gray" syndrome, associated with a violation of the glucuronization process in the liver.
Placenta permeability index for tetracycline 25-70%. These include tetracycline (category D), doxycycline (category D) and others. In animal experiments, the accumulation of these drugs in bone tissue, teeth bookmarks. Watch the deformation of the limbs, a decrease in body weight, fetal death, hydronephrosis.
Tetracyclines can cause liver fatty dystrophy, protein synthesis violation. Therefore, the use of tetracycline during pregnancy is contraindicated.
Aminoglycosides to varying degrees are able to undergo a placental barrier. Amicacin (Category C), streptomycin (category D) - 100%, Kanamycin (category D) - 20-50%. Aminoglycosides have overoxy, nephrotoxicity. The most toxic streptomycin. Toxicity is maximally manifested when recepting drugs from 12 to 20 week of pregnancy. A similar properties have gentamicin (category C), Tobramycin (category C), Sizomycin. Aminoglycosides are contraindicated during pregnancy.
Antifungal preparations (nystatin, miconazole) applied locally in pregnant women do not have embryophortoxic effects. However, the systemic use of drugs is not recommended, since the consequences have been learned little.
Sulfanimide preparations overcome the placental barrier and penetrate the fetus. They are able to oust bilirubin due to protein, enhancing jaundice, increasing the danger of bilirubin encephalopathy. Sulfanimides of prolonged action are the greatest danger for pregnant women. Application is contraindicated during pregnancy combined preparations containing trimethoprium (Category C), which disrupts the synthesis of folic and nucleic acids in the tissues of the fetus.
Also during pregnancy, fluoroquinolones (category C) are contraindicated: offloxacin, ciprofloxacin.
Nitrofurans (Category B) are transmitted through a placenta and accumulate in an oily-free fluid in limited quantities, but they may cause blood hemolysis in the fetus due to the influence of glucose6 phosphate dehydrogenase. Not recommended the appointment of nitrofuran in the first trimester, at the end of pregnancy and in childbirth.
Metronidazole - antiprotozoic. Easily overcomes the placental barrier and penetrates the fetus. In animal experiments and in clinical observations, the fetotoxic effect of the drug is not marked, therefore it is believed that the metronidazole is safe. However, there is data on the ability of metronidazole to inhibit the series of liver enzymes of the fetus, there are also information about the teratogenic activity. The drug is contraindicated in the first trimester of pregnancy.
Anti-tuberculosis agents cause significant fetus lesions. In the case of a trimester of pregnancy of isonicotine hydrazides (isoniazid) in the first trimester (isoniazide), there are rude anomalies for the development of the fetus (anencephalia, heart disease, hydrocephalus, urinary bubble ectopia, hypospadia, anal injection and other). These drugs are neurotoxic and cause neuropilegia.
Antiviral drugs. Among antiviral drugs The most acceptable is the acyclovir (category C), but its purpose requires strict indications. The closer to the term of childbirth, it is prescribed, the smaller the consequences can be expected. With vicinfection, zidovudine (category C) from 14 weeks of pregnancy is used.
Antiwest means. Treatment It is necessary to start with vitamin B6 preparations (Category A) (pyridoxine, pyridoxal phosphate). In the event of ineffectiveness, metoclopramide is used, which is relatively safe.
Doxillamin and chlorpromazine are contraindicated in the last weeks of pregnancy. These drugs may cause fetal developmental defects.
Anticonvulsants. Among the anticonvulsants, the safest drug is magnesium sulfate. It does not have embryophortotoxic effect, serves as a drug of choice in the treatment of eclampsia. In case of epileptic convulsions, carbamazepine, clonazepama, ethosuximide (Category C) is possible. These preparations have a proven teratogenic effect associated with the damage to the nervous tube of the fetus, increase the risk of bleeding in the fetus. Contraindicated: Valproic acid, phenytoin, phenobarbital, as they have pronounced teratogenic properties.
Sedative and sleeping pills. The most appropriate from this group Buchariron and Skipidem. The use of benzodiazepines (diazepams, oxaisepams, chlordiazepoxide) is undesirable, as it increases the risk of developing malfunctions of the fetus (splitting of solid nose, upper lip, disruption of nervous development). The use of benzodiazepines can lead to medicinal depression of the fetus, newborn. Long-term use of high doses of these drugs with a dead pregnancy can entail the appearance of drug addiction in the fetus. Barbiturates are contraindicated (see "Anticonvulsant tools").
Many drug plants have a sedative and sleeping effect, which can be used, including in order to anesthetize labor. In charges include: peppermint leaves, tri-listed watch, valerian root, hopnation, daisy flowers, cumin seeds, fenhel fruits, etcher grass. It is recommended that the appointment of dietary supplements (Kavakava, an evening primrose oil, a gingko biloba extract, a gota of Cola).
Antidepressants. Many antidepressants consider teratogens, including amitriptyline (category D), clomipramine (CAT), imipramine (category D), northriptyline (category D). Monoaminoxidase inhibitors (MAO) are contraindicated during pregnancy. Relatively safe can be considered fluoxetine - inhibitor of the inverse seizure of serotonin. It can be used in the first trimester of pregnancy. Apply new antidepressants: Sethalin (Category B), Paroksetin (Category B). So far there is no data that they increase the risk of congenital malformations of the fetus.
Almost any drug directly or mediated through the maternal body has an impact on the development of the fetus. The pharmacological and teratogenic effect of most drugs on the fruit is not studied enough. Therefore, they need to be treated as potentially dangerous.
Under the conditions of increasing polypragmasia (unreasonable purpose of the combinations of drugs), it is necessary to remember that even out of pregnancy, the purpose of 1-5 drugs leads to the development of undesirable effects in 5% of patients, with simultaneous use of 15 complications of complications are observed in 54% of patients.
The situation is exacerbated during pregnancy.
Clinicians who prescribe medicines pregnant women should follow the following recommendations:
· Try to avoid any medications during the I trimester of pregnancy;
· To give preference to monotherapy using short-acting preparations;
· give preference local treatment, if possible;
· Use the minimum doses of the most secure preparation;
· Use the drug if the benefits of it exceeds the possible risk to the fetus;
The doctor, appointed pregnant medication, takes great responsibility for the life, mother's health and her child.
1. Embryotoxic action Medicines - the negative effect of matter on the zygota and blastocyst, which are in the lumen of phallopy pipes or in the uterine cavity. Most often, the result is the formation of coarse defects of development, which leads to the interruption of pregnancy, hypoxia of the fetus often arises, sometimes death, and in mothers - toxicosis of pregnant women (gestosis), spontaneous abortion.
Embryotoxic effects are characterized as intrauterine death in the early stages of the development of the embryo (the first weeks). According to the principle of "all or nothing."
Embryotoxic action is provided
- · Hormones (for example estranes),
- · Cytostatics (antimetabolites - inhibit certain biochemical processes critical for the reproduction of malignant tumor cells, that is, for the division, mitosis process, DNA replication, which affects and dividing nucleus cells),
- · Barbiturates,
- · Sulfanimide drugs,
- · Antibiotics (protein synthesis inhibit),
- · Nicotine.
- · Hormonal contraceptives are very dangerous. Reception should be discontinued at least 6 months before the planned pregnancy.
- 2. Teratogenic action - LAN ability to cause malformations of the fetus. It occurs approximately from 2 to16 weeks (during the period of the most intense tissue differentiation).
The teratogenic effect depends on a number of circumstances:
- 1. Pregnancy term. The most severe defects incompatible with life arise from the damaging effect in the early stages of embryogenesis (the first 56 days). They conclude in gross violations of the development of the brain, the cardiovascular system, the gastrointestinal tract. At the end of the given data, the teratogenic substance can cause less severe vices, often compatible with life (heart defects, limbs, sexual sphere), but it makes a person with disabilities. After 8 gestational weeks, when the differentiation of organs and tissues is mainly completed, but the development of the central nervous system, the reproductive tract, not the upper lip and the taking the woman receiving a teratogenic woman causes small morphological flavors, such as the incoming of the upper coat or lips, hand defects and reproductive tract.
- 2. The value of the dose and the duration of the use of teratogen is of great importance.
- 3. The teratogenesis contributes to the violation of the function of eliminating organs (liver and kidney).
There is a group of medicinal substances whose teratogenicity and whose use of pregnant women is unacceptable.
These include:
- · High doses of vitamin A-splitting of the sky,
- · Diphenin - anticonvulsant, antiarrhythmic agent and muscular relaxant (stabilization of neuronal membranes of the body of the nervous cell, axons and in the field of synapse) - mental retardation, microcephalus, shortened phalanges of fingers,
- · Androgens,
- · Anorexic drugs,
- · Antitumor,
- · Anti-epileptic,
- · Anti-estrogens (clomiphenecitrate, tamex-hairdryer) - Down syndrome, malformations of the nervous system
- · Antimalarial,
- · Indirect anticoagulants,
- · Progestogen,
- · Tetracycline tertogenic action possible ugliness.
- · Folic acid antagonists, trimethoprim, prametamine, their combined drugs (Biseptol, Bactrim) -Hidrocephalia
- · Cyticostatics,
- · Alcohol- 2% of all teratogenic effects (contributes to the emergence of alcohol syndrome, growth deficit, disorders of coordination of movements, hypotrophy of the fetus.)
- · Suspected: sulfonamides, glucocorticoids. Diazepam
- 3. Fethotoxic action- Violation of any function of the fetus as a result of the operation of the LAN on the fruit. C4 months before the end of pregnancy.
Remote:
- · Anaprilin-bradycardia of the fetus
- · Morphine-oppression of the respiratory center
- · Aminoglycosides (streptomycin, gentamicin, amikacin-links. With a 30s-subunit of bacterial ribosomes and violate protein biosynthesis in ribosomes, causing a break of the flow of genetic information in a cell). Aminoglycosides pass through the placenta and can have an nephrotoxic effect on the fetus, output. There are reports of the development of an irreversible bilateral congenital deafness.
- · Tyreostatics (Tiamazole, Iodine preparations) - congenital goiter, hypothyroidism
- · Levomycetin is a decrease in the number of leukocytes, anemia.
The pharmacological composition of the most efficient drugs is not required without the presence of chemicals. In this regard, many drugs are capable not only to heal, but also cause side effects. Toxic action is an uncharacteristic response of the body to the impact of any irritants. Various unexpected symptoms can be the result of damage to organs, tissues and various organism systems.
Causes of occurrence
The manifestation of complications caused by drug intake may be the following reasons:
- physico-chemical composition of the drug;
- senile or childhood receiving;
- the formation of products of decomposition of toxic substances poisoning the body;
- a weak general condition of the patient;
- excess dosage or improper reception of the drug;
- combining drugs incompatible with pharmacological properties;
- individual intolerance to one of the components of the drug, dysbiosis or allergies;
- reception of prohibited drugs during pregnancy and breastfeeding.
The toxic effect of drugs is usually applied selectively by acting on individual organs and tissues of the body. However, the sharp phase of its phase can provoke the launch of irreversible processes in several systems at the same time.
Mechanism of action
Almost every medicinal substance (LV) causes side effects, just not all of them show themselves. Reactions disappear after canceling the drug. However, for the patient there is a risk of developing "medicinal disease".
Two main aspects that help to avoid serious consequences are compliance with medical prescriptions and following the instructions for the drug.
The mechanism of toxic action is such that the time range from the moment of drug intake and before the manifestation of side effects does not have clear boundaries. They can reveal themselves as immediately after the adoption of the medicine and in a few weeks, months and even years. A sharp toxic effect manifests itself sharply and in the shortest possible time. Most often, the patient's liver and buds suffer from, since these organs participate in filtering and eliminating the decay products of poisons and harmful substances. Excessive load can lead to their full dysfunction.
Embryotoxic action
Prior to the attachment of the fetal egg to the placenta (the first 1-3 weeks after the fertilization of the egg) drugs affect its development in the lumen of phallopy pipes and on the process of moving to the uterus. Such an action threatens the appearance of various deformities in a newborn. Among the drugs, the reception of which is capable of a greater degree to negatively affect the embryo, there are antimetabolites and antimicotic drugs: colchicine, fluorouracil, mercaptopurine.
Teratogenic action
Since the beginning of the second month of pregnancy and until its end turns out a teratogenic effect. It was at the end of an eight-week period from the beginning of gestation in the fetus develops a skeleton and laid internal organs. Its fabric at this moment is very sensitive to the effects of external negative factors. Congenital deformities in the form of anomalies for the development of a skeleton or organ deficiency is a consequence of the teratogenic action of medicines that the mother took the mother during pregnancy.
It was revealed that after taking strong sleeping pills and tranquilizing drugs, such as talided, the child was born with incorrectly developed limbs having a shape of a last. The teratogenic toxic effects may also have antitumor drugs and alcohol received in female organism During conception.
Fethotoxic action
When the term of pregnancy reaches 20 weeks, at this stage all systems and organs are already formed and functioning as well as in an adult. During this period, due to the reception of medicines, a fetotoxic effect affects the future of the child. Anticoagulants affect the blood formation system, the coal function of blood clotting. Sleeping and severe sedatives negatively reflected on the central nervous system. Ethyl alcohol consumption, even in drugs, in small amounts and narcotic substances, also cause reactions from the CNS, can lead to the development of cerebral paralysis.
Mutagenic action
Carcinogenic
The carcinogenic effect consists in the ability of the drug to cause cell destruction and absorbing their adjacent tissues, which leads to the formation of malignant tumors.
Precautions
Given that the toxic effect of the LV is capable of imparting irreparable harm, the appointment of any preparations of a pregnant woman should be carried out by an obstetrician-gynecologist. This does not mean that in the position it is impossible to take anything. In order to avoid heavy consequencesIt should be carefully studying the instructions and the composition of the means and adequately evaluate the benefit value for the Mother / Risk for the Fetal.
Weak sedatives on herbs, vitamin complexes and folic acid can be accepted during this period. . However, drug intake should pass under the careful observation of the doctor. An important aspect is to track the state of the future mother and the development of the fetus on blood and urine analysis.
Modern pharmacology introduces only those LVs that are not capable of providing embryotoxic, teratogenic, fetotoxic, mutagenic and carcinogenic effect on the human body and on the child inside the maternal womb.
Allergy and dysbiosis
Dysbiosis
Violation of the composition of natural microflora is also a manifestation of toxic action. Dysbiosis (dysbiosis) is a lack of beneficial bacteria in the intestines, oral cavity and vagina, which is replaced by pathogenic and fungal organisms. Such a phenomenon is a consequence of taking antibiotics and some hormonal drugs.
Toxic effect due to dysbiosis is manifested in the following reactions:
- from the gearbox: frequent liquid chair, spasms and abdominal pain, bloating and meteorism;
- from the female sexual system: vaginal candidiasis, the distinguishing symptoms of which are itching and white curls of the vagina;
- in case of violation of the microflora of the oral cavity: stomatitis, ulcers and wounds on the gums and heaven, thrush in the language, an increase in body temperature, an unpleasant smell.
To prevent such reactions, the intake of antibiotics is combined with antifungal agents (nystatin, pimafucine) probiotics and prebiotics (bifidumbacterin, lazziffil, etc.).
Allergic reactions due to toxic effects arise against the background of the perception of the components of the LV as antigens. The dosage in this case does not play the role and the severity of the side effects are different: it can be skin rashes, and anaphylaxis.
Four types of allergic reactions are isolated:
- Instant. Developed within a few hours after taking toxic drug. The dosage can be minimal. Immunoglobulins E react with antigens, which leads to the allocation of histamine. The manifestations of toxic action can be the most different: skin itching, swelling, rash, runny nose, tear, swelling of the throat and anaphylaxis. Antibiotics of a number of penicillin can provoke an immediate reaction.
- Cytotoxic. Nonspecific cell reaction caused by IGG and IGM antibodies to determine. Allergens are their own fabrics, modified under the action of LV. Hematological diseases due to such an impact are able to cause hypotensive products, sulfonamides, antibiotics.
- Immunocomplex. This is the result of the joint action of allergen with IGM, IGE and IGG. The victim has an allergic alveolitis and serum disease, the symptoms of which is manifested by itching, urticaria, a feverish state. Such an effect may be observed after receiving penicillin and sulfanimide.
- Delayed. These are skin manifestations arising after the medication in the form of cream, ointment, emulsion or suspension on the skin. In addition, the slow motion manifestation of allergies may be the result of a transfers of an organ or rheumatism. In this case, the early phase is absent, immediately occurs the reaction of the immune system, due to lymphocytes and microphages.
You can prevent allergies only in the only way - do not take medicines that cause it, and warn your doctor about the development of an allergic reaction to a particular drug. If the drug is accepted for the first time in life, you must first introduce it under the skin or smear a small area on the back of the forearm and look at the result.
The toxic effect of drugs is most often due to overdose. Individual reaction to drugs used in medical practice arises less frequently, and allergies usually provoke paracetamol and penicillin. Prepress which response will be followed by the reception of this or that drug is impossible. However, such LVs, as antibiotics, tranquilizers and hormones, should be accepted strictly under the supervision of the doctor, in order not to launch an irreversible process and not harm their health.