Analgesics

Promedol (trimeperidine hydrochloride). Promedol is known to be a synthetic substitute for morphine and has a pronounced analgesic effect. A decrease in pain sensitivity under the influence of promedol develops after subcutaneous administration in 10-15 minutes. The duration of analgesia is 3-4 hours. The maximum permissible single dose of promedol during labor is 40 mg (2% solution - 2 ml) subcutaneously or intramuscularly. When combined with neuroleptic drugs, the effect of promedol is enhanced.

According to numerous clinical and experimental data, promedol increases uterine contractions. The stimulating effect of promedol on the smooth muscles of the uterus was established in an experiment and its use was recommended simultaneously for pain relief and intensification of labor. It has pronounced antispasmodic and labor-accelerating properties.

Estocin is a synthetic analgesic, along with cholinolytic and antispasmodic effects, it also has a pronounced analgesic effect. The analgesic effect develops quite quickly with any method of administration of the drug (orally, intramuscularly or intravenously), but the duration of the analgesic effect does not exceed an hour.

The analgesic effect of estocin is inferior to promedol by about 3 times, however, it is less toxic than promedol. Estocin depresses breathing less, does not increase the tone of the vagus nerve; has a moderate antispasmodic and anticholinergic effect, reduces spasms of the intestines and bronchi; does not cause constipation. In obstetric practice, it is used internally in doses of 20 mg.

Pentazocine (lexir, fortral) has a central analgesic effect, the intensity of which almost reaches the effect of opiates, but does not cause depression of the respiratory center and other side effects, addiction and addiction. The analgesic effect occurs 15-30 minutes after intramuscular administration and lasts about 3 hours. Lexir does not affect the motor function of the gastrointestinal tract, excretory organs, sympathetic-adrenal system and causes a moderate short-term cardiostimulating effect. Teratogenic effects have not been described, but it is not recommended to administer the drug in the first trimester of pregnancy, it is administered at a dose of 0.03 g (30 mg), and in case of severe pain - 0.045 g (45 mg) intramuscularly or intravenously.

Fentanyl is a derivative of piperidine, but its analgesic effect is 200 times greater than that of morphine and 500 times greater than that of promedol. It has a pronounced depressor effect on the respiratory center.

Fentanyl causes selective blockade of some adrenergic structures, as a result of which after its administration the reaction to catecholamines decreases. Fentanyl is used in a dose of 0.001-0.003 mg per 1 kg of the mother's body weight (0.1-0.2 mg - 2-4 ml of the drug).

Dipidolor. Synthesized in 1961 in the laboratory of the Janssen company. Based on pharmacological experiments, it was established that dipidolor is 2 times more powerful than morphine in its analgesic activity and 5 times more powerful than pethidine (promedol).

The toxicity of dipidolor is extremely low - this drug does not have subacute and chronic toxicity. The therapeutic range of dipidolor is 1 }£ times greater than that of morphine, and 3 times greater than that of pethidine (promedol). The drug does not have a negative effect on the functions of the liver, kidneys, cardiovascular system, does not change the electrolyte balance, thermoregulation, or the state of the sympathetic-adrenal system.

When administered intravenously, the effect of dipidolor does not appear immediately, but when administered intramuscularly, subcutaneously, and even orally, it appears after 8 minutes; the maximum effect develops after 30 minutes and lasts from 3 to 5 hours. In 0.5% of cases, nausea occurs, vomiting was not observed. A reliable antidote is nalorphine.

Ataralgesia with dipidolor and seduxen has potentiated synergism. The analgesic activity of the combination exceeds the sum of the analgesic effects of separate use of dipidolor and seduxen in the same doses. The degree of neurovegetative protection of the body increases with a combination of dipidolor and seduxen by 25-29%, and respiratory depression is significantly reduced.

The basis of modern anesthetic care is combined analgesia, which creates conditions for targeted regulation of body functions. Research shows that the problem of pain relief is increasingly developing into targeted correction of pathophysiological and biochemical shifts.

Dipidolor is usually administered intramuscularly and subcutaneously. Intravenous administration is not recommended due to the risk of respiratory depression. Taking into account the intensity of pain, age and general condition of the woman, the following doses are used: 0.1-0.25 mg per 1 kg of the woman's body weight - an average of 7.5-22.5 mg (1-3 ml of the drug).

Like all morphine-like substances, dipidolor suppresses the respiratory center. When the drug is administered intramuscularly in therapeutic doses, respiratory depression is extremely insignificant. It usually occurs in exceptional cases only in case of overdose or hypersensitivity of the patient. Respiratory depression quickly ceases after intravenous administration of a specific antidote - naloxone (nalorphine) in a dose of 5-10 mg. The antidote can be administered intramuscularly or subcutaneously, but then its effect occurs more slowly. Contraindications are the same as for morphine and its derivatives.

Ketamine.The drug is available as a stabilized solution in 10 and 2 ml vials, containing 50 and 10 mg of the drug in 1 ml of 5% solution, respectively.

Ketamine (Calypsol, Ketalar) is a low-toxic drug; acute toxic effects occur only with overdose of more than twenty times; does not cause local tissue irritation.

The drug is a strong anesthetic. Its use causes deep somatic analgesia, sufficient for abdominal surgical interventions without the use of additional anesthetic agents. The specific state in which the patient is during anesthesia is called selective "dissociative" anesthesia, in which the patient seems to be "switched off" rather than asleep. For minor surgical interventions, intravenous drip administration of subnarcotic doses of ketamine (0.5-1.0 mg/kg) is recommended. In this case, surgical anesthesia is achieved in many cases without turning off the patient's consciousness. The use of standard doses of ketamine (1.0-3.0 mg/kg) leads to the preservation of residual postoperative analgesia, which allows for 2 hours to completely eliminate or significantly reduce the amount of administered drugs.

It is necessary to note a number of adverse effects of ketamine use: the appearance of hallucinations and agitation in the early postoperative period, nausea and vomiting, convulsions, accommodation disorders, spatial disorientation. In general, such phenomena occur in 15-20% of cases when using the drug in its "pure" form. They are usually short-lived (several minutes, rarely tens of minutes), their severity is rarely significant, and in the vast majority of cases there is no need to prescribe special therapy. The number of such complications can be almost reduced to zero by introducing benzodiazepine drugs and central neuroleptics into premedication. The administration of diazepam (for example, 5-10 mg for short-term surgery, 10-20 mg for long-term) or droperidol (2.5-7.5 mg) before and/or during surgery almost always eliminates "awakening reactions". The occurrence of these reactions can be largely prevented by limiting sensory afferent flows, i.e. closing the eyes in the awakening phase, avoiding premature personal contact with the patient, as well as talking and touching the patient; they also do not occur with the combined use of ketamine together with inhalation narcotic substances.

Ketamine spreads rapidly and evenly throughout the body in almost all tissues, and its concentration in blood plasma decreases by half in an average of 10 minutes. The half-life of the drug in tissues is 15 minutes. Due to the rapid inactivation of ketamine and its low content in the body's fat depots, cumulative properties are not expressed.

Ketamine is most intensively metabolized in the liver. The breakdown products are eliminated primarily in the urine, although other routes of excretion are possible. The drug is recommended for intravenous or intramuscular use. When administered intravenously, the initial dose is 1-3 mg/kg of body weight, with narcotic sleep occurring on average within 30 seconds. An intravenous dose of 2 mg/kg is usually sufficient to produce anesthesia for 8-15 minutes. When administered intramuscularly, the initial dose is 4-8 mg/kg, with surgical anesthesia occurring within 3-7 minutes and lasting from 12 to 25 minutes.

Induction of anesthesia occurs quickly and, as a rule, without excitation. In rare cases, short-term and weakly expressed tremor of the limbs and tonic contractions of the facial muscles are observed. Anesthesia is maintained by repeated intravenous administration of ketamine at a dose of 1-3 mg / kg every 10-15 minutes of surgery or by intravenous drip administration of ketamine at an infusion rate of 0.1-0.3 mg / (kg - min). Ketamine is well combined with other anesthetic agents and can be used with the addition of narcotic analgesics, inhalation narcotics.

Spontaneous breathing under anesthesia is maintained at a fairly effective level when using clinical doses of the drug; only a significant overdose (3-7 times) can lead to respiratory depression. Very rarely, with intravenous rapid administration of ketamine, short-term apnea occurs (maximum 30-40 sec), which, as a rule, does not require special therapy.

The effect of ketamine on the cardiovascular system is associated with the stimulation of a-adrenoreceptors and the release of norepinephrine from peripheral organs. The transient nature of changes in blood circulation when using ketamine does not require special therapy and these changes are short-lived (5-10 min).

Thus, the use of ketamine allows for anesthesia to be performed while maintaining spontaneous breathing; the risk of aspiration syndrome is significantly lower.

There are quite contradictory data in the literature on the effect of ketamine on uterine contractility. This is probably due to both the concentration of the anesthetic in the blood and the tone of the autonomic nervous system.

Currently, ketamine is used as an induction anesthetic for cesarean section, as a monoanesthetic to ensure abdominal delivery and “minor” obstetric operations, and also for the purpose of pain relief during labor with intramuscular administration of the drug using drip perfusion.

Some authors use a combination of ketamine with diazepam or synthodian at 2 ml for the purpose of pain relief during labor, which is equivalent to the effectiveness of 5 mg of droperidol with ketamine intramuscularly at a dose of 1 mg/kg.

E. A. Lancev et al. (1981) developed methods of pain relief during labor, induction of anesthesia, anesthesia with ketamine against the background of artificial ventilation of the lungs or spontaneous breathing, as well as pain relief of minor obstetric operations with ketamine. The authors came to the conclusion that ketamine has a relatively small number of contraindications. These include the presence of late toxicosis of pregnancy, post-severance of various etiologies in the systemic and pulmonary circulation, psychiatric diseases in the anamnesis. Bertoletti et al. (1981) indicate that with intravenous administration of 250 mg of ketamine per 500 ml of 5% glucose solution, 34% of women in labor experienced a slowdown in the rate of uterine contractions, which correlated with the administration of oxytocin. Methfessel (1981) investigated the effect of ketamine monoanesthesia, ketamine-seduxen anesthesia, and ketamine monoanesthesia with preliminary preparation with tocolytics (partusisten, dilatol) on intrauterine pressure indices. It was found that preliminary (prophylactic) administration of partusisten significantly weakens the effect of ketamine on intrauterine pressure. Under conditions of combined ketamine-seduxen anesthesia, this undesirable effect is completely blocked. In an experiment on rats, ketamine only slightly changes the reactivity of the myometrium to bradykinin, but causes a gradual loss of sensitivity of the rat myometrium to prostaglandin.

Caloxto et al. also demonstrated in experiments on isolated rat uterus to determine the mechanism of ketamine action its inhibitory effect on the myometrium, apparently due to inhibition of Ca ²⁺ transport. Other authors did not detect any inhibitory effect of ketamine on the myometrium or on the course of labor in clinical settings.

No negative effect of ketamine on the condition of the fetus and newborn child was detected either during labor pain relief or during operative delivery; no effect of ketamine on cardiotocogram parameters or acid-base status of the fetus and newborn was noted.

Thus, the use of ketamine expands the arsenal of means for providing cesarean section and pain relief during labor using various techniques.

Butorphanol (moradol) is a strong analgesic for parenteral use and is similar in action to pentazocine. In strength and duration of action, speed of onset of effect it is close to morphine, but is effective in smaller doses; A dose of 2 mg of moradol causes strong analgesia. Since 1978, moradol has been widely used in clinical practice. The drug penetrates the placenta with minimal impact on the fetus.

Moradol is administered intramuscularly or intravenously in a dosage of 1-2 ml (0.025-0.03 mg/kg) when persistent pain occurs and the cervix is 3-4 cm dilated. An analgesic effect was achieved in 94% of women in labor. With intramuscular administration, the maximum effect of the drug was observed after 35-45 minutes, and with intravenous administration - after 20-25 minutes. The duration of analgesia was 2 hours. No negative effect of moradol in the dosages used on the condition of the fetus, contractile activity of the uterus, or the condition of the newborn was found.

When using the drug, caution should be exercised in patients with high blood pressure.

Tramadol (tramal) - has a strong analgesic activity, gives a quick and long-lasting effect. However, it is inferior in activity to morphine. When administered intravenously, it has an analgesic effect in 5-10 minutes, when administered orally - in 30-40 minutes. It acts for 3-5 hours. It is administered intravenously at a dose of 50-100 mg (1-2 ampoules, up to 400 mg, 0.4 g) per day. In the same dose, it is administered intramuscularly or subcutaneously. No negative effect on the body of the mother in labor or contractile activity of the uterus has been identified. An increased amount of meconium impurity in the amniotic fluid has been noted, without changing the nature of the fetal heartbeat.

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