Narcotic analgesics

The classic representative of narcotic analgesics is morphine. It causes depression of the central nervous system, relieves pain of various origins. The name was given in honor of the son of the ancient Greek god of sleep, Morpheus.

Opium (the frozen milky juice of immature carotid poppy heads) has been the main source of morphine since prehistoric times in medical practice.

In Chinese, Arabic, Indian medicine, in the XV-XVI centuries it was used as an antidiarrheal and intoxicating agent. Opium contains more than 20 alkaloids, which by chemical structure are either derivatives of piperidine phenanthrene – possess the properties of narcotic analgesics (morphine, codeine), or isoquinoline (papaverine, etc.) – have a myotropic antispasmodic effect on the smooth muscles of internal organs and blood vessels. Narcotic analgesics by origin are divided into:

1) natural, obtained from opium – morphine, codeine, omnopon;

2) synthetic -trimeperidine hydrochloride (promedol), fentanyl, pentazocine (lexir, fortral), pyritramide (dipidolor), tramadol (tramal).

Painkillers isolated from opium are commonly referred to as opiates, and their synthetic substitutes opioids or opiate-like agents.

According to the selectivity and the nature of the effect on opiate receptors, narcotic analgesics are divided into:

1) agonists: morphine, trimeperidine hydrochloride (promedol), fentanyl, pyritramide (dipidolor) – are used as painkillers;

2) antagonist agonists: pentazocine (used as an analgesic), nalorphine is used for moderate overdose of narcotic analgesics (except pentazocine);

3) antagonists: naloxone, naltrexone (they are antagonists of all analgesics, including pentazocine).

Narcotic analgesics are used for any injuries (domestic, operating, wounds, etc.), diseases accompanied by severe pain (malignant neoplasms, myocardial infarction, etc.).

Morphine is the main alkalioid of opium and makes up about 10% of its mass. The main effects are associated with the effect on the central nervous system.

The effect of morphine on its various departments is not the same: it inhibits some structures, while it excites others. Morphine gives deep analgesia, but there is no loss of consciousness, no amnesia is observed. The drug causes euphoria, has a calming and hypnotic effect; the morphine dream is shallow, rich in vivid dreams. By suppressing pain irritations, morphine even exacerbates the perception of sound, light and tactile irritations.

A characteristic action of morphine is inhibition of the respiratory center. In small doses, it causes a decrease and deepening of the respiratory movements, and in large doses it reduces not only the frequency, but also the depth of breathing. At the same time, ventilation decreases and hypoxia develops. With an overdose of morphine, death occurs from paralysis of the respiratory center. Penetrating the placenta, he, like other narcotic analgesics, can cause asphyxiation of the newborn. Morphine is dangerous for respiratory failure (emphysema, bronchial asthma). All narcotic analgesics, inhibiting the cough center of the medulla oblongata, suppress cough, but increase the accumulation of secretions in the respiratory tract (there is no expectorant effect). Vomiting, which can be observed with morphine, is associated with the initiation of chemoreceptor trigger (“trigger”) zones of the medulla oblongata. However, especially in large doses, the drug has an antiemetic effect (blockage of the vomiting center). Naturally, with morphine poisoning, emetics are useless.

Morphine constricts the pupils (excitation of the centers of the oculomotor nerves). For chronic drug poisoning, “point” pupils are characteristic. By stimulating the vagus nerve nucleus, morphine causes bradycardia and can lower blood pressure. The effect of morphine and other narcotic analgesics on the intestines is also partially related to the effect on opiate receptors. Morphine enhances the spasm of the sphincters of the gastrointestinal tract, which leads to a slowdown, and sometimes the cessation of the passage of intestinal contents from one section to another – a “blocking effect”, which is also facilitated by a decrease in bile secretion (spasm of the distal portion of the common bile duct – the Oddy sphincter inhibits it discharge and increases pressure in the gallbladder); the drug inhibits the secretion of the digestive glands and pancreas. Morphine reduces diuresis by cramping the sphincters of the bladder. In addition, urination is inhibited due to increased secretion of antidiuretic hormone (vasopressin). A decrease in the activity of metabolic processes with the introduction of morphine, a decrease in the respiratory rate and the expansion of peripheral vessels against the background of inhibition of the thermoregulation center, leads to a decrease in body temperature (hypothermia). Morphine even in therapeutic doses can cause an increase in intracranial pressure (due to respiratory depression and the accumulation of carbon dioxide in the blood, the vessels of the brain expand and swelling increases), therefore it is not indicated for traumatic brain injury. Morphine helps release histamine from mast cells, causing swelling of the bronchial mucosa and bronchospasm, hyperemia, itching, sweating.

Morphine is administered orally and parenterally. The effect lasts 3-6 hours. When administered, the effect develops in 20-30 minutes. Morphine-like products are not well absorbed from the gastrointestinal tract and are biotransformed in the liver upon first passage through it. Therefore, to obtain a quick effect, drugs are administered parenterally. After subcutaneous administration, the action begins in 10-15 minutes. In shock, the peripheral vessels are narrowed, and the absorption of the drug with subcutaneous administration slows down, so morphine is administered intramuscularly or slowly intravenously. Regional analgesia is also used when narcotic analgesics are directly delivered to the structures of the spinal cord (epidural and subarachnoid administration). With this appointment, a direct effect on the neuronal systems is achieved, and lower doses are required to obtain a painkiller effect (the likelihood of developing complications is reduced). In recent years, morphine began to be used periodically (0.2-0.5 ml of a 1% solution of the drug in 10 ml of isotonic sodium chloride solution): the effect occurs in 10-15 minutes and lasts for 8-12 hours.

Narcotic analgesics penetrate well into parenchymal organs and into skeletal muscles, but poorly in brain tissue (about 1%). Morphine is excreted as metabolites mainly by the kidneys.

Almost all the effects of narcotic analgesics, except for painkillers, are undesirable, especially such as addiction, drug dependence and respiratory depression, which limit the use of morphine-like agents. The development of drug dependence (mental and physical) is the main disadvantage of treatment with narcotic analgesics and morphine in particular. With addiction to morphine, withdrawal symptoms begin 6-12 hours after drug administration, it is very difficult and can end fatally.

Treatment for morphine addiction is difficult, lengthy, carried out in a hospital and not always successful – relapses are frequent. The principle of treatment is the gradual replacement of morphine with longer-acting narcotic analgesics (most often methadone) against the background of symptomatic therapy. Methadone, unlike morphine, acts longer (72 hours), is less likely to cause addiction, withdrawal symptoms are easier. Prescribe the drug inside, daily, reducing the dose to 20%.

Acute morphine poisoning is characterized by respiratory depression, a sharp narrowing of the pupil (with severe hypoxia, they can be dilated), cyanosis, hypothermia, coma. Death occurs from paralysis of the respiratory center. Main

treatment is aimed at restoring breathing; the most effective is mechanical ventilation with intubation of the trachea.

Morphine-like antagonists are nalorphine (an antagonist agonist) and “pure” opiate antagonists lacking morphine-like activity – naloxone, naltrexone. In case of morphine poisoning, in addition, the stomach is repeatedly washed (a certain part of it is secreted by the mucous membrane and can be resorbed) with a 0.05-0.1% potassium permanganate solution (oxidizes morphine) and a suspension of activated carbon. Assign a saline laxative.

Omnopon is new galenic, that is, opium free from ballast substances, which is a mixture of hydrochlorides of its main alkaloids, including morphine (50%). Unlike morphine, omnopon is less likely to cause smooth muscle spasms, as it contains substances with an antispasmodic effect – papaverine, narcotine (isoquinoline derivatives).

Codeine (methylmorphine) is an opium alkaloid. It has all the pharmacological properties of morphine, but less pronounced. It is used as an antitussive and for mild pain, often in combination with non-narcotic analgesics.

Trimeperidine (promedol) is a synthetic drug slightly weaker than morphine, has a moderate antispasmodic effect, less depresses the respiratory center, less pronounced vagal effect and less likely to cause nausea and vomiting. It is used for pain – traumatic, cancerous, postoperative, birth, myocardial infarction, renal and hepatic colic.

Fentanyl – in terms of analgesic effect, is many times superior to morphine, acting quickly (after 1-2 minutes) and very short (15-30 minutes). The fast and strong analgesic effect is explained by high lipophilicity and easy passability through the blood-brain barrier. With intravenous administration of large doses, bronchospasm, bradycardia and respiratory depression are sometimes possible. Fentanyl is widely used in combination with the short-acting antipsychotic droperidol for neuroleptanalgesia (NLA) or ataralgesia (with a tranquilizer sibazonum). Both methods give a powerful calming effect, neurovegetative inhibition, loss of pain sensitivity while maintaining consciousness.

Pentazocine (fortral) – refers to a group of antagonist agonists. Morphine is inferior in strength and duration of the analgesic effect, but it depresses breathing to a lesser extent and causes constipation less often, drug dependence does not develop so naturally (compared to other narcotic analgesics). Pentazocine activates the central mechanisms of the sympathoadrenal system, and, as a result, increases blood pressure, and can cause tachycardia. Therefore, it is undesirable to use with coronary heart disease. The effects of pentazocine are removed only by naloxone (not nalorphine!).

Pyritrimide (dipidolor) – by its analgesic effect, is 1.5-2 times higher than morphine, acts quickly, less depresses breathing, less often causes nausea and vomiting. Used for “balanced analgesia” (ataralgesia).

Tramadol (tramal) – discharges morphine in painkiller activity, acts quickly and for longer; depresses breathing slightly, does not significantly affect blood circulation and the gastrointestinal tract.

Naloxone is a “pure” competitive antagonist of narcotic analgesics. It removes the effect of morphine-like agents on opiate receptors (more on m- and k-receptors). The duration of the effect of naloxone is about 1-3 hours, and it must be re-entered, since narcotic analgesics act for a long time. Against the background of an overdose of narcotic analgesics, intravenous administration of naloxone normalizes respiration after 1-2 minutes. In addition, the drug is used for alcoholic coma, shock conditions, and some mental illnesses.

Morphine-like antagonists include naltrexone and nalorphine,

Naltrexone acts like naloxone, but for a longer time – up to 24-40 hours, used orally, in tablets, the effect occurs after 1-2 hours.

Nalorphine is an antagonist agonist, rarely used in case of overdose of narcotic analgesics. The analgesic effect of the drug is not used, since nalorphine causes agitation and hallucinations.

Narcotic analgesics are used for traumatic, postoperative pain, for malignant neoplasms, myocardial infarction, renal and hepatic colic (necessarily with antispasmodics). Widely used in anesthesiology for sedation (enhance the action of general and local anesthetics) and antipsychotics.

Preparations of different groups that have a central analgesic effect.

Clonidine (clonidine) – refers to central antihypertensive drugs, but has recently been widely used as a non-opioid analgesic in anesthesiology practice, in the postoperative period, in obstetrics, with cardiogenic traumatic and oncological pains. It even surpasses morphine in its analgesic effect, but it does not depress respiration and does not cause drug dependence. In addition, clonidine normalizes hemodynamic changes in pain of various origins and weakens its motor and emotional affective manifestations. The mechanism of action of the drug is associated with an effect on central adrenopositive structures (through the excitation of central a2-adrenergic receptors), which are involved in the activity of the antinociceptive system. Clonidine has a sedative effect, prolongs and potentiates the action of CNS depressants, and can also be used for sedation in anesthesiology. Sometimes used to relieve opiate and alcohol withdrawal.

Amitriptyline (a tricyclic antidepressant) has an analgesic effect. It is explained by a decrease in neuronal uptake of serotonin in the descending paths and inhibition of the transmission of pain impulses from afferent neurons to the posterior horns of the spinal cord. Amitriptyline can be prescribed for chronic pain, especially against the background of elements of depression.

Ketalar (ketamine) is a non-inhalation anesthetic, along with a general anesthetic, and has an analgesic property. The analgesic effect is associated with activation of serotonin and opiate receptors in the brain. After anesthesia, analgesia lasts 3-4 hours. Side effects – psychomotor agitation, hallucinations (easily eliminated by seduxen, as well as the introduction of antihypoxant – amtizol).

The antiepileptic agent carbamazepine, which is widely used for trigeminal neuralgia, has an analgesic effect.

Preparations:

Morphine hydrochloride

The drug is prescribed orally and subcutaneously.

Available in tablets of 0.01 g, in ampoules and syringe tubes of 1 ml of 1% solution.

Codeine

The drug is taken orally.

Available in powder and tablets of 0.015 g with sodium bicarbonate.

Omnopon

Enter inside and under the skin.

Available in powder, in ampoules of 1 ml of 1% and 2% solution.

Promedol (Trimeperidine)

Apply subcutaneously, intramuscularly and inside.

Available in tablets of 0.025 g; in ampoules and syringe tubes, 1 ml of 1% and 2% solution.

Pentazocine hydrochloride

Applied orally, subcutaneously, intramuscularly, intravenously.

Available in tablets of 0.05 g of pentazocine hydrochloride; in 1 ml ampoules containing 0.03 g of the drug in the form of lactate.

Fentanyl

The drug is administered intramuscularly and intravenously.

Available in ampoules of 2 and 5 ml of 0.005% and solution.