The strongest painkillers. Analgesics Means with maximum analgesic activity

These drugs selectively reduce, suppress pain sensitivity, without significantly affecting other types of sensitivity and without disturbing consciousness (analgesia - loss pain sensitivity; an - negation, algos - pain). Since ancient times, doctors have tried to save the patient from pain. Hippocrates 400 BC e. wrote: "... the removal of pain is a divine work." Based on the pharmacodynamics of the respective drugs, modern painkillers are divided into 2 large groups:

I-I - narcotic analgesics or the morphine group. This group of funds is characterized by the following points (conditions):

1) have a strong analgesic activity, allowing them to be used as highly effective pain relievers;

2) these drugs can cause drug addiction, that is, addiction, drug dependence associated with their special effect on the central nervous system, as well as the development of a painful condition (withdrawal) in people with developed dependence;

3) in case of an overdose, the patient develops a deep sleep, turning successively into anesthesia, coma, and, finally, ending with a stop in the activity of the respiratory center. Therefore, they got their name - narcotic analgesics.

The second group of drugs are non-narcotic analgesics, the classic representatives of which are: aspirin or acetylsalicylic acid. There are many drugs here, but all of them are not addictive, because they have different mechanisms of action.

Let's analyze I-th group means, namely drugs of the morphine group or narcotic analgesics.

Narcotic analgesics have a pronounced inhibitory effect on the central nervous system. Unlike drugs that depress the central nervous system indiscriminately, it manifests itself as an analgesic, moderately hypnotic, antitussive effect that depresses the respiratory centers. In addition, most narcotic analgesics cause drug (mental and physical) dependence.

The most prominent representative of this group of funds, because of which this group got its name, is morphine.

Morphini hydrochloridum (table at 0.01; amp. 1% - 1 ml). The alkaloid morphine is isolated from opium (Greek - opos - juice), which is the frozen, dried juice of unripe bolls of the soporific poppy (Papaver somniferum). Poppy is native to Asia Minor, China, India, Egypt. Morphine got its name from the name of the ancient Greek god of dreams, Morpheus, who, according to legend, is the son of the god of sleep, Hypnos.

Morphine in opium contains 10-11%, which is almost half of the proportion of all alkaloids present in it (20 alkaloids). They have been used in medicine for a long time (5000 years ago as an anesthetic, antidiarrheal). Despite the synthesis of morphine carried out in 1952 by chemists, it is still obtained from opium, which is cheaper and easier.

According to the chemical structure, all pharmacologically active opium alkaloids are either phenanthrene derivatives or isoquinoline derivatives. The alkaloids of the phenanthrene series include: morphine, codeine, thebaine, etc. It is the phenanthrene alkaloids that are characterized by a pronounced inhibitory effect on the central nervous system (analgesic, antitussive, hypnotic, etc.).

For isoquinoline derivatives, a direct antispasmodic effect on smooth muscles is characteristic. A typical isoquinoline derivative is papaverine, which has no effect on the central nervous system, but affects smooth muscles, especially in a state of spasm. Papaverine acts in this case as an antispasmodic.

PHARMACOLOGICAL PROPERTIES OF MORPHINE

1. Effect of morphine on the central nervous system

1) Morphine primarily has an analgesic or analgesic effect, while doses that do not significantly alter the functions of the central nervous system have an analgesic effect.

The analgesia caused by morphine is not accompanied by blurred speech, impaired coordination of movements, touch, vibration sensitivity, and hearing are not weakened. The analgesic effect is the main one for morphine. AT modern medicine it is one of the most powerful painkillers. The effect develops a few minutes after the injection. More often, morphine is administered intramuscularly, s / c, but it can also be intravenously. The action lasts 4-6 hours.

As you know, pain consists of 2 components:

a) the perception of pain, depending on the threshold of pain sensitivity of a person;

b) mental, emotional reaction to pain.

In this regard, it is important that morphine sharply inhibits both components of pain. It increases, firstly, the threshold of pain sensitivity, thus reducing the perception of pain. The analgesic action of morphine is accompanied by a feeling of well-being (euphoria).

Second, morphine changes the emotional response to pain. In therapeutic doses, it may not even completely eliminate the sensations of pain, but patients perceive it as something extraneous.

How and in what way does morphine effect these effects?

MECHANISM OF ACTION OF NARCOTIC ANALGESICS.

In 1975, Hughes and Kosterlitz discovered specific "opiate" receptors of several types in the nervous system of humans and animals, with which narcotic analgesics interact.

Currently, five types of these opiate receptors are distinguished: mu, delta, kappa, sigma, epsilon.

It is with these opiate receptors that various endogenous (produced in the body itself) peptides with high analgesic activity normally interact. Endogenous peptides have a very high affinity (affinity) for these opiate receptors. The latter, as it became known, are located and function in various parts of the central nervous system and in peripheral tissues. Due to the fact that endogenous peptides have a high affinity, they are also called in the literature in relation to opiate receptors LIGANDS, that is (from Latin - ligo - I bind) directly binding to receptors.

There are several endogenous ligands, they are all oligo-peptides containing different amounts of amino acids and united under the name "ENDORPHINS" (that is, endogenous morphines). Peptides, which include five amino acids, are called enkephalins (methionine-enkephalin, lysine-enkephalin). Currently, this is a whole class of 10-15 substances that have in their molecules from 5 to 31 amino acids.

Enkephalin, according to Hughes, Kosterlitz are "substances in the head".

Pharmacological effects of enkephalins:

Release of pituitary hormones;

Memory change;

Breathing regulation;

Modulation of the immune response;

Anesthesia;

A condition similar to catatonia;

Convulsive seizures;

Body temperature regulation;

Appetite control;

reproduction functions;

sexual behavior;

Reactions to stress;

Decreased blood pressure.

MAIN BIOLOGICAL EFFECTS OF ENDOGENOUS OPIATES

The main effect, role, biological function of endorphins is the inhibition of the release of "pain neurotransmitters" from the central endings of afferent unmyelinated C-fibers (including norepinephrine, acetylcholine, dopamine).

As you know, these mediators of pain can be, first of all, substance P (a peptide of amino acids), cholecystokinin, somatostatin, bradykinin, serotonin, histamine, prostaglandin. Pain impulses propagate along the C- and A-fibers (A-delta fibers) and enter the posterior horns of the spinal cord.

When pain occurs, a special system of enkephalinergic neurons, the so-called antinociceptive (anti-pain) system, is normally stimulated, neuropeptides are released, which has an inhibitory effect on the pain system (nociceptive) of neurons. The end result of the action of endogenous peptides on opiate receptors is an increase in the threshold of pain sensitivity.

Endogenous peptides are very active, they are hundreds of times more active than morphine. Currently, they are isolated in their pure form, but in very small quantities, they are very expensive, while they are mainly used in experiments. But there are already results in practice. Synthesized, for example, the domestic peptide DALARGIN. The first results have been obtained, and already in the clinic.

In case of insufficiency of the antinoceceptive system (anti-pain enkephalinergic), and this happens with an excessively pronounced or prolonged damaging effect, pain has to be suppressed with the help of painkillers - analgesics. It turned out that the site of action of both endogenous peptides and exogenous drugs are the same structures, namely, opiate receptors of the nociceptive (pain) system. In this regard, morphine and its analogues are opiate receptor agonists. Separate endo- and exogenous morphines act on different opiate receptors.

In particular, morphine acts mainly on mu receptors, enkephalins on delta receptors, etc. ("responsible" for pain relief, respiratory depression, reduction in CCC frequency, immobilization).

Thus, narcotic analgesics, in particular morphine, playing the role of endogenous opiate peptides, being essentially imitators of the action of endogenous ligands (endorphins and enkephalins), increase the activity of the antinociceptive system and enhance its inhibitory effect on the pain system.

In addition to endorphins, serotonin and glycine, which are synergists of morphine, function in this antinociceptive system. Influencing predominantly on mu-receptors, morphine and other drugs of this group mainly suppress aching, pulling pain associated with the summation of nociceptive impulses coming from the spinal cord along a non-specific path to the non-specific nuclei of the thalamus, disrupting its distribution to the superior frontal, parietal gyrus of the cerebral cortex (that is, the perception of pain), as well as to other parts of it, in particular, to the hypothalamus, the amygdala complex, in which vegetative, hormonal, and emotional reactions to pain are formed.

By suppressing this pain, drugs inhibit the emotional reaction to it, as a result of which narcotic analgesics prevent dysfunction of the cardiovascular system, the occurrence of fear, and suffering associated with pain. Strong analgesics (fentanyl) are able to suppress the conduction of excitation along a specific nociceptive pathway.

By stimulating enkephalin (opiate) receptors in other brain structures, endorphins and narcotic analgesics affect sleep, wakefulness, emotions, sexual behavior, convulsive and epileptic reactions, autonomic functions. It turned out that almost all known systems of neurotransmitters are involved in the implementation of the effects of endorphins and morphine-like drugs.

Hence, various other pharmacological effects morphine and its preparations. So, the 2nd effect of morphine, a sedative and hypnotic effect. The sedative effect of morphine is very pronounced. Morpheus is the son of the god of sleep. The sedative effect of morphine is the development of drowsiness, some obscuration of consciousness, a violation of the ability of logical thinking. From sleep caused by morphine, patients easily wake up. The combination of morphine with hypnotics or other sedatives makes the CNS depression more pronounced.

3rd effect - the effect of morphine on mood. Here the influence is twofold. In some patients, and more often in healthy individuals, after a single administration of morphine, there is a feeling of dysphoria, anxiety, negative emotions, no pleasure, and a decrease in mood. As a rule, this occurs in healthy individuals who do not have indications for the use of morphine.

With repeated administration of morphine, especially when there are indications for the use of morphine, the phenomenon of euphoria usually develops: there is an increase in mood with a feeling of bliss, lightness, positive emotions, pleasantness throughout the body. Against the background of emerging drowsiness, reduced physical activity, difficulty in concentrating attention develops, and a feeling of indifference to the outside world arises.

Thoughts and judgments of a person lose their logical sequence, the imagination becomes fantastic, bright colorful pictures, visions appear (dream world, "high"). The ability to engage in art, science, creativity is lost.

The occurrence of these psychotropic effects is due to the fact that morphine, like other analgesics of this group, directly interacts with opiate receptors localized in the cerebral cortex, hypothalamus, hippocampus, amygdala complex.

The desire to experience this state again is the cause of a person's mental dependence on the drug. Thus, it is euphoria that is responsible for the development of drug addiction. Euphoria can come even after one injection.

The 4th pharmacological effect of morphine is associated with its effect on the hypothalamus. Morphine inhibits the thermoregulatory center, which can lead to a sharp decrease in body temperature in case of morphine poisoning. In addition, the effect of morphine on the hypothalamus is also related to the fact that, like all narcotic analgesics, it stimulates the release of antidiuretic hormone, which leads to urinary retention. In addition, it stimulates the release of prolactin and growth hormone, but delays the release of luteinizing hormone. Under the influence of morphine appetite decreases.

5th effect - morphine, like all other drugs of this group, has a pronounced effect on the centers of the medulla oblongata. This action is ambiguous, since it excites a number of centers, and a number depresses.

Respiratory depression occurs most easily in children. Inhibition of the respiratory center is associated with a decrease in its sensitivity to carbon dioxide.

Morphine inhibits the central links of the cough reflex and has a pronounced antitussive activity.

Narcotic analgesics, like morphine, can contribute to the stimulation of neurons in the chemoreceptor trigger (starter) zone of the bottom of the IV ventricle, causing nausea and vomiting. Morphine itself depresses the vomiting center in large doses, so repeated administration of morphine does not cause vomiting. In this regard, the use of emetics in morphine poisoning is useless.

6th effect - the effect of morphine and its drugs on the vessels. Therapeutic doses have little effect on blood pressure and the heart, toxic doses can cause hypotension. But morphine causes dilatation of peripheral blood vessels, especially capillaries, partly through a direct action and partly through the release of histamine. Thus, it can cause reddening of the skin, an increase in its temperature, swelling, itching, sweating.

EFFECT OF MORPHINE ON THE GIT AND OTHER SMOOTH MUSCLE ORGANS

The influence of narcotic analgesics (morphine) on the gastrointestinal tract is attributed mainly to their increase in the activity of the neurons of the n center. vagus, and to a lesser extent due to a direct effect on the nervous elements of the gastrointestinal tract wall. In this regard, morphine causes a strong spasm of the smooth muscles of the intestine, imocecal and anal sphincters and at the same time reduces motor activity, reducing peristalsis (GIT). The spasmodic effect of morphine is most pronounced in the area duodenum and large intestine. The secretion of saliva, hydrochloric acid of gastric juice and the secretory activity of the intestinal mucosa are reduced. The passage of feces slows down, the absorption of water from them increases, which leads to constipation (morphine obstipation - an increase in the tone of all 3 muscle groups). Morphine and its analogues increase the tone of the gallbladder, contribute to the development of spasm of the sphincter of Oddi. Therefore, although the analgesic effect alleviates the patient's condition with biliary colic, the course of the pathological process itself is aggravated.

EFFECT OF MORPHINE ON OTHER SMOOTH MUSCLE FORMATIONS

Morphine increases the tone of the uterus and Bladder, ureters, which is accompanied by "urinary haste". At the same time, the visceral sphincter is reduced, which, if there is insufficient response to urges from the bladder, leads to urinary retention.

Morphine increases the tone of the bronchi and bronchioles.

INDICATIONS FOR THE USE OF MORPHINE

1) Acute pain, threatening the development of pain shock. Examples: severe trauma (fractures of tubular bones, burns), relief postoperative period. In this case, morphine is used as an analgesic, anti-shock agent. For the same purpose, morphine is used for myocardial infarction, pulmonary embolism, acute pericarditis, spontaneous pneumothorax. To relieve sudden onset pain, morphine is given intravenously, which quickly reduces the risk of shock.

In addition, morphine as an analgesic is used for colic, for example, intestinal, renal, hepatic, etc. However, it must be clearly remembered that in this case morphine is administered together with the antispasmodic atropine, and only when the doctor is sure of the correctness of the diagnosis .

2) Chronic pain in hopelessly dying patients with a humane goal (example: hospices - hospitals for hopeless cancer patients; admission by the hour). In general, chronic pain is a contraindication to the use of morphine. Only in hopeless, dying tumor carriers, doomed, the administration of morphine is mandatory.

3) As a means of premedication during anesthesia, before anesthesia, that is, in anesthesiology.

4) As an antitussive for cough that threatens the life of the patient. By this indication morphine is prescribed, for example, for major operations, chest injuries.

5) In acute left ventricular failure, that is, with cardiac asthma. In this case, the effect is due to a decrease in the excitability of the central nervous system and pathological dyspnea. It causes expansion of peripheral vessels, as a result of which there is a redistribution of blood from the system of pulmonary arteries to dilated peripheral vessels. This is accompanied by a decrease in blood flow and a decrease in pressure in the pulmonary artery and CVP. Thus, the work of the heart is reduced.

6) In acute pulmonary edema.

SIDE EFFECTS OF MORPINE

The breadth of the pharmacological effects of morphine also determines its many adverse reactions. These are, first of all, dysphoria, constipation, dry mouth, cloudy thinking, dizziness, nausea and vomiting, respiratory depression, headache, fatigue, paresthesia, bradycardia. Sometimes there are intolerance in the form of tremor and delirium, as well as allergic reactions.

CONTRAINDICATIONS TO THE USE OF MORPHINE

There are no absolutes, but there is a whole group of relative contraindications:

1) early childhood(up to 3 years) - danger of respiratory depression;

2) in pregnant women (especially at the end of pregnancy, during childbirth);

3) at the most various types respiratory failure (emphysema, bronchial asthma, kyphoscoliosis, obesity);

4) with severe head injuries (increased intracranial pressure; in this case, morphine, further increasing intracranial pressure, causes vomiting; vomiting, in turn, increases intracranial pressure and thus a vicious circle is formed).

In our country, a very powerful analgesic with a long-term effect has been created on the basis of morphine - MORPHILONG. It is a new drug containing morphine hydrochloride and narrowly fractionated polyvinylpyrrolidone. Morfilong as a result acquires a longer duration of action (22-24 hours of its analgesic effect) and a greater intensity of the effect. Less pronounced side effects. This is its advantage over morphine (the duration is 4-6 times longer than the duration of the action of morphine). Used as an analgesic prolonged remedy:

1) in the postoperative period;

2) with a pronounced pain syndrome.

OMNOPON (Omnoponum in amp. 1 ml - 1% and 2% solution). Omnopon is a new-galenic opium preparation in the form of a mixture of 5 opium alkaloids. It contains 48-50% morphine and 32-35% other alkaloids of both the phenanthrene and isoquinoline series (papaverine). In this regard, omnopon has a lesser spasmodic effect. In principle, the pharmacodynamics of omnopon is similar to that of morphine. However, omnopon is still used together with atropine. Indications for use are almost the same.

In addition to morphine, many synthetic and semi-synthetic drugs have found application in medical practice. These drugs were created with 2 goals:

1) to get rid of poppy plantations;

2) so that addiction is not formed in patients. But this goal failed, since all narcotic analgesics have common mechanisms of action (via opiate receptors).

Of considerable interest is PROMEDOL, which is a synthetic drug derived from piperidine.

Promedolum (table - 0.025; amp. 1 ml - 1% and 2% solution). In terms of analgesic activity, it is 2-4 times inferior to morphine. The duration of action is 3-4 hours. Rarely causes nausea and vomiting, to a lesser extent depresses the respiratory center. Unlike morphine, promedol reduces the tone of the ureters and bronchi, relaxes the cervix and slightly increases the contraction of the uterine wall. In this regard, promedol is preferred for colic. In addition, it can be used during childbirth (according to indications, since it depresses fetal breathing to a lesser extent than morphine, and also relaxes the cervix).

In 1978, a synthetic analgesic appeared - MORADOL, which is a derivative of phenanthrene in terms of its chemical structure. A similar synthetic drug is TRAMAL. Moradol (butorphanol tartrate) when administered intramuscularly and intramuscularly provides a high degree of analgesic efficacy, while analgesia occurs faster than with the introduction of morphine (after 30-60 minutes, morphine - after 60 minutes). The action lasts 3-4 hours. However, it has significantly less side effects and most importantly, a very low risk of developing physical dependence, even with prolonged use, since moradol rarely causes euphoria (it acts mainly on other delta opiate receptors). In addition, it depresses breathing to a limited extent, even in large doses. Use: for the same indications as morphine, but in the case of a long-term need for use. In therapeutic doses, it does not depress the respiratory center, it is safe for the mother and fetus.

Another synthetic representative of piperidine-phenanthrene derivatives is FENTANIL. Fentanyl has a very high analgesic activity, surpasses morphine in activity (100-400 times). A distinctive feature of fentanyl is the short duration of pain relief it causes (20-30 minutes). The effect develops in 1-3 minutes. Therefore, fentanyl is used for neuroleptanalgesia in conjunction with the neuroleptic droperidol (talomonal).

This type of analgesia is used when the patient must be conscious, for example, with myocardial infarction. The very form of anesthesia is very convenient, since the patient does not respond to pain irritation (analgesic effect) and treats everything that happens with complete indifference (neuroleptic effect, consisting of a super-sedative and a strong tranquilizing effect).

Opium alkaloid CODEIN stands apart (Codeinum in Table 0.015). As an analgesic, it is much weaker than morphine. It has a weaker affinity for opiate receptors. The antitussive effect of codeine is weaker than that of morphine, but quite sufficient for practice.

Benefits of codeine:

1) unlike morphine, it is well absorbed when taken orally;

2) codeine depresses respiration less;

3) less causes drowsiness;

4) has less spasmodic activity;

5) addiction develops more slowly to codeine.

INDICATIONS FOR THE USE OF CODEINE:

1) with dry, raw, unproductive cough;

2) the second stage of the fight against chronic pain in a cancer patient (WHO), according to a three-stage scheme. Codeine (50-150 mg every 5 hours) plus a non-narcotic analgesic, plus adjuvants (glucocorticoids, antidepressants, anticonvulsants, psychotropic, etc.).

ACUTE POISONING WITH MORPINE AND MORPHINE-LIKE DRUGS

Acute poisoning morphine can occur with an overdose of the drug, as well as with accidental intake of large doses in patients with addiction. In addition, morphine can be used for suicidal purposes. For adults, the lethal dose is 250 mg.

In acute morphine poisoning, the clinical picture is characteristic. The patient's condition is very serious. At first, sleep develops, passing into the stage of anesthesia, then coma, leading to paralysis of the respiratory center.

The clinical picture consists primarily of respiratory depression, its slowing down. The skin is pale, cold, cyanotic. There is a decrease in body temperature and urination, at the end of poisoning - a decrease in blood pressure. Bradycardia develops, a sharp narrowing of the pupil (point size of the pupil), at the end of hypoxia, the pupil expands. Death occurs due to respiratory depression or shock, pulmonary edema, and secondary infection.

TREATMENT of patients with acute morphine poisoning is based on the same principles as the treatment of acute intoxication with barbiturates. Assistance measures are distinguished specific and non-specific.

SPECIFIC MEASURES OF ASSISTANCE are associated with the introduction of specific morphine antagonists. The best antagonist is NALOXONE (narcan). There is practically no naloxone in our country, and therefore a partial antagonist, NALORFIN, is used more often.

Naloxone and nalorphine eliminate the effect of morphine and its drugs on opiate receptors and restore normal CNS function.

Narorphine, a partial antagonist of morphine, in its pure form (single drug) acts like morphine (causes an analgesic effect, but weaker, depresses respiration, gives bradycardia, narrows the pupils). But against the background of the administered morphine, nalorphine manifests itself as its antagonist. Nalorphine is usually used in / in a dose of 3 to 5 mg, if necessary, repeating injections after 30 minutes. Its effect literally occurs at the "tip of the needle" - during the first minute of administration. In case of an overdose of these drugs, a person poisoned with morphine can quickly develop withdrawal syndrome.

NON-SPECIFIC AID MEASURES are associated with the removal of unabsorbed poison. Moreover, gastric lavage should be done even with parenteral administration of morphine, since it is partially secreted by the gastrointestinal mucosa into the intestinal lumen. It is necessary to warm the patient, if convulsions occur, use anticonvulsants.

With deep respiratory depression, artificial ventilation of the lungs is performed.

CHRONIC MORPINE POISONING, as a rule, is associated with the development of addiction to it. The development of addiction, drug addiction is naturally accompanied by repeated administration of narcotic analgesics. Distinguish between physical and mental dependence.

A manifestation of the formed PHYSICAL DEPENDENCE on narcotic analgesics is the occurrence of a withdrawal or withdrawal syndrome when the repeated administration of morphine is stopped. Withdrawal syndrome consists of a series characteristic features: 6-10-12 hours after the last injection of morphine, the morphine user develops rhinorrhea, lacrimation, terrible yawning, chills, goose bumps, hyperventilation, hyperthermia, mydriasis, muscle pain, vomiting, diarrhea, tachycardia, weakness, sweating, disorders sleep, hallucinations, anxiety, restlessness, aggressiveness.These symptoms last for 2-3 days.To prevent or eliminate these phenomena, the addict is ready to do anything, even crime.Constant use of the drug leads a person to physical and mental degradation.

The mechanism of withdrawal development is associated with the fact that narcotic analgesics, by activating opiate receptors on the feedback principle (as in endocrinology), inhibit the release, and perhaps the synthesis of endogenous opiate peptides, gradually replacing their activity. As a result of the abolition of analgesics, there is a deficiency of both the previously administered analgesic and the endogenous peptide. An abstinence syndrome develops.

Before physical dependence develops mental dependence. The basis for the emergence of mental dependence is euphoria, sedation and an indifferent attitude to environmental influences that disturb a person. In addition, the repeated administration of morphine causes very pleasant sensations for the morphine user in abdominal cavity, sensations of unusual warmth in the epigastric region and lower abdomen, reminiscent of those with intense orgasm.

In addition to mental and physical dependence, there is a third sign of drug addiction - the development of tolerance, stability, addiction. In this regard, the addict is constantly forced to increase the dose of the analgesic.

Treatment of addiction to morphine is not fundamentally different from the treatment of addiction to alcohol or barbiturates. Treatment of drug addicts is carried out in special institutions, but the results are not yet encouraging (a few percent). Frequent development of deprivation syndrome (withdrawal), relapses of addiction.

There is no special tool. Use fortifying, vitamins. It is easier to prevent addiction than to treat it. The danger of developing drug addiction is main reason restrictions on the use of these drugs in medicine. From pharmacies they are released only on special prescriptions, the drugs are stored according to the "A" list.

NON-NARCOTIC ANALGESICS are painkillers, analgesics that do not have a significant effect on the central nervous system, do not cause drug addiction and anesthesia. In other words, unlike narcotic analgesics, they do not have a sedative and hypnotic effect; euphoria, addiction and drug dependence do not occur with their use.

Currently, a large group of drugs has been synthesized, among which the so-called:

1) old or classic non-narcotic analgesics

2) new, more modern and more anti-inflammatory action - the so-called non-steroidal anti-inflammatory drugs - NSAIDs.

According to the chemical structure, old or classic non-narcotic analgesics are divided into 3 main groups:

1) derivatives salicylic acid(ortho-hydroxybenzoic acid) - salicylates:

a) Acetylsalicylic acid - (aspirin, Acidum acetylsalicylicum);

b) sodium salicylate (Natrii salicylas).

More drugs in this group: salicylamide, methyl salicylate, as well as diflunisal, benortan, tosiben.

2) pyrazolone derivatives:

a) amidopyrine (Amidopyrinum, in the table at 0, 25) - discontinued as a monopreparation, used in combined products;

b) analgin (Analginum, in tab. 0, 5; amp. 1; 2 ml - 25% and 50% solution);

c) butadione (Butadionum, in the table at 0.15);

3) aniline derivatives:

a) phenacetin (Phenacetinum - in combined tablets);

b) paracetamol (Paracetamolum, in tab. 0, 2).

Non-narcotic analgesics have 3 main pharmacological effects.

1) Analgesic or analgesic effect. Analgesic activity non-narcotic analgesics It manifests itself with certain types of pain: mainly with neuralgic, muscle, joint pain, as well as with headache and toothache.

At severe pain associated with trauma, abdominal surgery, malignant formations they are practically ineffective.

2) Antipyretic or antipyretic effect, manifested in febrile conditions.

3) Anti-inflammatory action, expressed to varying degrees in various compounds of this group.

Let's start with salicylates. The main drug in this group is acetylsalicylic acid or ASPIRIN (Acidum acetylsalicylicum in Table 0.1 for children; 0.25; 0.5) (AA).

Salicylates have been known for a long time, they are already more than 130 years old, they were the first drugs that have a specific anti-inflammatory effect, combined with an analgesic and antipyretic effect. The complete synthesis of acetylsalicylic acid was carried out in 1869. Salicylates have since become widespread in medical practice.

Salicylates, including AA (aspirin), have 3 main pharmacological effects.

1) Anesthetic or analgesic effect. This effect is somewhat less pronounced, especially in visceral pain, than that of morphine. AA acid is effective drug with the following types of pain: with headache; toothache; pain emanating from muscle and nervous tissues (myalgia, neuralgia), with joint pain (arthralgia), as well as pain emanating from the small pelvis.

The analgesic effect of non-narcotic analgesics, in particular salicylates, is especially pronounced in inflammation.

2) The second effect of AA is antipyretic (antipyretic). This effect is to reduce feverish, but not normal body temperature. Usually, as antipyretic drugs, salicylates are indicated starting from a temperature of 38.5-39 degrees, that is, at a temperature that violates the general condition of the patient. This provision applies especially to children.

At lower body temperatures, salicylates are not recommended as antipyretics, since fever is one of the manifestations of the body's defense response to infection.

3) The third effect of salicylates, and hence AA, is anti-inflammatory. The anti-inflammatory effect is manifested in the presence of inflammation in the connective tissue, that is, with various disseminated systemic tissue diseases or collagenoses (rheumatism, rheumatoid arthritis, ankylosing spondylitis, arthralgia, systemic lupus erythematosus).

The anti-inflammatory effect of AA begins after reaching a constant level of salicylates in the tissues, and this happens after 1-2 days. The intensity of the pain reaction decreases in the patient, exudative phenomena decrease, which is clinically manifested by a decrease in swelling and edema. Usually the effect persists during the period of drug use. The reduction of inflammation associated with the restriction (inhibition) of the exudative and proliferative phases of inflammation by salicylates is a causal element of the analgesic effect, that is, the anti-inflammatory effect of salicylates also enhances their analgesic effect.

It should be said that in salicylates, all 3 listed pharmacological effects are approximately equal in severity.

In addition to the above effects, salicylates also have an antiaggregatory effect on blood platelets, and with long-term use, salicylates also have a desensitizing effect.

MECHANISM OF ACTION OF SALICILATES

The action of salicylates is associated with inhibition (inhibition) of the synthesis of prostaglandins of various classes. These highly active compounds were discovered in 1930 by Swedish scientists. Normally, prostaglandins are present in tissues in trace amounts, but even with minor influences (toxic substances, some hormones), their concentration in tissues increases sharply. At their core, prostaglandins are cyclic fatty acids with 20 carbon atoms in the chain. They arise from free fatty acids, primarily from arachidonic acid, ingested with food. They are also formed from linoleic and linolenic acids after their conversion into arachidonic acid. These unsaturated acids are part of phospholipids. From phospholipids, they are released under the action of phospholipase 2 or phospholipase A, after which they become a substrate for the biosynthesis of prostaglandins. Calcium ions are involved in the activation of prostaglandin synthesis.

Prostaglandins are cellular, local hormones.

The first step in the biosynthesis of prostaglandins (PG) is the oxidation of arachidonic acid, carried out by the PG-cyclogenase-peroxidase complex associated with microsomal membranes. A circular structure of PGG-2 appears, which, under the action of peroxidase, passes into PGH-2. From the obtained products - cyclic endoperoxides - under the influence of PG-isomerase, "classical" prostaglandins - PGD-2 and PGE-2 are formed (the two in the index means the presence of two double bonds in the chain; the letters indicate the type and position of the side radicals of the cyclopentane ring).

Under the influence of PG-reductase, PGF-2 is formed.

Enzymes catalyzing the synthesis of other PGs have been found; having special biological properties: PG-I-isomerase, -oxocyclase, catalyzing the formation of prostacyclin (PG I-2) and PG-thromboxane -A-isomerase, catalyzing the synthesis of thromboxane A-2 (TxA-2).

The decrease, suppression of the synthesis of prostaglandins under the action of salicylates is associated primarily with the inhibition of PG synthesis enzymes, namely the inhibition of cyclooxygenases (COX). The latter leads to a decrease in the synthesis of pro-inflammatory prostaglandins (especially PGE-2) from arachidonic acid, which potentiates the activity of inflammatory mediators - histamine, serotonin, bradykinin. Prostaglandins are known to cause hyperalgesia, that is, they increase the sensitivity of pain receptors to chemical and mechanical stimuli.

Thus, salicylates, inhibiting the synthesis of prostaglandins (PGE-2, PGF-2, PGI-2), prevent the development of hyperalgesia. The threshold of sensitivity to pain stimuli increases. The analgesic effect is most pronounced in inflammation. Under these conditions, the release and interaction of prostaglandins and other "inflammatory mediators" occur in the focus of inflammation. Prostaglandins cause the expansion of arterioles in the focus of inflammation and hyperemia, PGF-2 and TxA-2 - narrowing of venules - stasis, both prostaglandins increase the permeability of the vascular wall, contributing to the exudation of fluid and white blood elements, increase the effect on the vascular wall and other inflammatory mediators. TxA-2 promotes the formation of platelet thrombi, endoperoxides initiate free radical reactions that damage tissues. Thus, Pg contribute to the implementation of all phases of inflammation: alteration, exudation, proliferation.

Suppression of the participation of inflammatory mediators in the development of the pathological process by non-narcotic analgesics, in particular salicylates, leads to the utilization of arachidonic acid through the lipoxygenase pathway and to an increased formation of leukotrienes (LTD-4, LTS-4), including the slowly reacting substance of anaphylaxis, which causes vasoconstriction and limitation of exudation. The inhibition of the synthesis of prostaglandins by salicylates explains their ability to suppress pain, reduce the inflammatory response, as well as feverish body temperature. The antipyretic effect of salicylates is to reduce feverish, but not normal body temperature. an increase in the concentration of PgE-2 in the cerebral fluid, which is manifested by an increase in heat production and a decrease in heat transfer.Salicylates, inhibiting the formation of PGE-2, restore the normal activity of the neurons of the thermoregulation center.As a result, heat transfer increases by radiating heat from the surface of the skin and evaporating copious amounts of sweat. this practically does not change.The hypothermic effect of salicylates is quite distinct only if they are used against the background of fever.With normothermia, they practically do not change body temperature.

INDICATIONS FOR THE USE of salicylates and acetylsalicylic acid (Aspirin)

1) AA is used as an analgesic for neuralgia, myalgia, arthralgia (joint pain). Usually acetylsalicylic acid is used for the symptomatic treatment of aching and chronic pain. The drug is effective for many types of pain (with shallow, moderate intensity of postoperative and postpartum pain, as well as pain caused by soft tissue injury, thrombophlebitis of superficial veins, headache, dysmenorrhea, algomenorrhea).

2) As an antipyretic for fever, for example, rheumatic etiology, with fever of infectious and inflammatory genesis. The appointment of salicylates in order to reduce body temperature is advisable only with very high temperature, which adversely affects the patient's condition (39 or more degrees); i.e., with febrile fever.

3) As an anti-inflammatory agent for the treatment of patients with inflammatory processes, in particular with arthritis and myositis, acetylsalicylic acid is mainly used. It reduces the inflammatory response, but does not interrupt it.

4) As an antirheumatic agent, with collagenoses (rheumatism, rheumatoid arthritis, SLE, etc.), i.e. with systemic diffuse diseases connective tissue. In this case, all effects are used, including the desensitizing effect.

When used in high doses, salicylates dramatically reduce signs of inflammation for 24-48 hours. Reduced pain, swelling, immobility, increased local temperature, redness of the joint.

5) As an anti-aggregating agent for the prevention of the formation of lamellar-fibrin thrombi. For this purpose, aspirin is used in small doses, approximately 150-300 mg / day. Daily intake of such doses of the drug has proven itself for the prevention and treatment of intravascular coagulation, for the prevention of myocardial infarction.

6) Small doses of ASA (600-900 mg) - when used prophylactically, they prevent symptoms of food intolerance. In addition, AA is effective for diarrhea, as well as for radiation sickness.

SIDE EFFECTS

1) The most common complication in the use of ASA is irritation of the gastric mucosa (a consequence of the suppression of the synthesis of cytoprotective prostaglandins, in particular PGI-2 prostacyclin), the development of erosions, sometimes with bleeding. The dual nature of this complication: AA - acid, which means that it irritates the mucous membrane itself; inhibition of the synthesis of prostaglandins in the mucosa, - prostacyclin, the second contributing factor.

In a patient, salicylates cause dyspepsia, nausea, vomiting, and with prolonged use, they can have an ulcerogenic effect.

2) Frequent complication when taking salicylates, there are hemorrhages (hemorrhages and bleeding), which are the result of inhibition of platelet aggregation by salicylates and antagonism in relation to vitamin K, which is necessary for the activation of prothrombin, proconvertin, IX and X coagulation factors, as well as to maintain the normal structure of the vascular wall. Therefore, the use of salicylates not only disrupts blood clotting, but also increases the fragility of blood vessels. To prevent or eliminate this complication, vitamin K preparations are used. Most often, vikasol, but it is better to prescribe phytomenadione, an analogue of vitamin K, which is faster absorbed, more effective and less toxic.

3) In high doses, AA causes cerebral symptoms, manifested by tinnitus, ringing in the ears, hearing loss, anxiety, and in a more severe case - hallucinations, loss of consciousness, convulsions, respiratory failure.

4) In persons suffering from bronchial asthma or obstructive bronchitis, salicylates can cause an increase in bronchospasm attacks (which is a consequence of the suppression of the synthesis of antispasmodic prostaglandins and the predominant formation of leukotrienes, including the slowly reacting substance of anaphylaxis from their common precursor - arachidonic acid).

5) Some patients may have hypoglycemic conditions - a consequence of the suppression of the synthesis of PGE-2 and thereby eliminating its inhibitory effect on the release of insulin from the beta cells of the islet tissue of the pancreas.

6) When using AA at the end of pregnancy, delivery may be delayed by 3-10 days. Newborns whose mothers, according to indications, took salicylates (AA) at the end of pregnancy may develop severe vascular diseases lungs. In addition, salicylates (AA) taken during pregnancy can disrupt the course of normal organogenesis, in particular, lead to non-closure of the ductus botalis (due to inhibition of the synthesis of prostaglandins necessary for normal organogenesis).

7) Rarely (1: 500), but there are allergic reactions for salicylates. Intolerance can be manifested by skin rashes, urticaria, itching, angioedema, thrombocytopenic purpura.

Salicylic acid is an ingredient in many substances, including fruits (apples, grapes, oranges, peaches, plums), some soaps, fragrances and drinks (especially birch sap).

Of the salicylates, in addition to AA, SODIUM SALICYLATE is used - this drug gives an analgesic effect, which is only 60% of that of Aspirin; its analgesic and anti-inflammatory effects are even weaker, so it is used relatively rarely. It is used mainly for systemic diffuse tissue diseases, for collagenoses (RA, rheumatism). A similar drug is methyl salicylate.

The second group of non-narcotic analgesics are pyrazolone derivatives. This group of drugs includes AMIDOPIRINE, BUTADION, and ANALGIN.

AMIDOPIRINE (PYRAMIDONE) (Amidopyrinum powder; tab. 0, 25). Pyros - fire. It is a powerful analgesic and antipyretic.

The drug is completely and rapidly absorbed from the intestine and almost completely metabolized in the body. However, due to high toxicity, in particular, a pronounced inhibitory effect on hematopoiesis, amidopyrine is practically not used in the clinic; It is excluded from use as an independent agent and is included only in some combined preparations.

ANALGIN (Analginum; powder; in tab. 0, 5; in amp. 1 and 2 ml - 25% and 50% solution). Analgin is chemically and pharmacologically similar to amidopyrine. Analgin is highly soluble in water, so it can also be administered parenterally. As with amidopyrine, this drug has a more pronounced analgesic effect than antipyretic, and especially anti-inflammatory effects.

Analgin is used for short-term analgesic and antipyretic effects in case of neuralgia, myositis, headache, toothache. In this case, as a rule, a tablet form is used. In more pronounced cases, when it is necessary to quickly have an effect, analgin injections are used. At the same time, analgin quickly reduces elevated temperature body. Assign analgin as an antipyretic only in case of febrile fever, when the drug is the first aid. Enter intramuscularly. The child must be well remembered not to inject 1 ml or more, as there may be a lytic temperature drop, which will lead to a temperature collapse. The child is injected with 0.3-0.4 ml. As a rule, in this case, dimed is added to the dipyrone solution.

roll. Treatment with analgin is associated with the risk of complications (primarily from the side of the blood), and therefore its use as an analgesic and antipyretic is not justified, when salicylates or other agents are equally effective.

BARALGIN (Baralginum) - developed in Germany. Very close to analgin drug. In tablet form, it comes from Bulgaria as SPASMOLGON. Baralgin consists of analgin, to which 2 more synthetic substances are added (one of which has a papaverine-like effect, the second has a weak ganglioblocking effect). From this it is clear that baralgin is indicated primarily for renal, hepatic, intestinal colic. It is also used for spasms of cerebral vessels, for headaches, and for migraines. Available in both tablets and injectable form.

Currently, a whole series of combined preparations containing analgin (Maksigan, Spazmalgin, Spazgan, Veralgan, etc.)

BUTADION (Butadionum; in the table at 0.15). It is believed that butadion in analgesic activity is approximately equal to analgin, and in anti-inflammatory activity is significantly higher than it. It is therefore used as an anti-inflammatory drug. According to this indication, butadion is prescribed for lesions of extra-articular tissues (bursitis, tendonitis, synovitis) of rheumatic and non-rheumatic origin. Indicated for ankylosing spondylitis, rheumatoid arthritis, osteoarthritis.

The maximum concentration of butadione in the blood, as well as other pyrazolone derivatives, is reached after about 2 hours. The drug actively binds to plasma proteins (98%). Long-term treatment with butadione leads to stimulation of hepatic microsomal enzymes. Due to this, butadion is sometimes used in small doses (0.005 g / kg per day) in children with hyperbilirubinemia. Butadion reduces the reabsorption of urates in the final tubules, which contributes to the removal of these salts from the body of these salts. In this regard, they are used for gout.

The drug is toxic, hence the side effects:

1) like all pyrazolone derivatives, with prolonged use it can cause anorexia, sensations of heaviness in the epigastrium, heartburn, nausea, vomiting, diarrhea, peptic ulcers. It can cause hepatitis, so it is prescribed only for 5-7 days;

2) like all pyrazolone drugs, butadione inhibits hematopoiesis (leukopenia, anemia, thrombocytopenia) to agranuloditosis;

3) during treatment with butadione, swelling may develop, since it retains sodium ions in the body, and hence water (reduces natriuresis); this can lead to congestive heart failure or even pulmonary edema.

REOPIRIN (Rheopyrinum) - a drug that is a combination of amidopyrine and butadione, has a pronounced anti-inflammatory and analgesic activity. It is used only as an anti-inflammatory agent for arthritis, rheumatic lesions, lumbago, adnexitis, parametritis, neuralgia. In addition, it, contributing to the excretion of urate salts from the body, is prescribed for gout. Available in both tablet and injectable dosage forms (Gedeon Rihter).

Recently, a group of new analgesics has been synthesized, which are called non-steroidal anti-inflammatory drugs - NSAIDs.

ANILINE DERIVATIVES (or more precisely, para-aminophenol).

Two drugs should be mentioned here: phenacetin and paracetamol.

Paracetamol as an active analgesic and antipyretic substance was discovered in 1893 by von Mehring. In 1995, it was suggested that paracetamol is a metabolite of phenacetin, and in 1948, Brody and Axelrod proved the role of paracetamol as the main metabolite of phenacetin. In our time, paracetamol is widely used as an antipyretic and analgesic agent at the stage of pre-medical pharmacological care to the patient. In this regard, paracetamol is one of the characteristic drugs of the OTC market (OTC - jver the counter), i.e. drugs sold without a doctor's prescription. One of the first pharmacological companies officially presenting OTC drugs, and in particular paracetamol (panadol in various dosage forms), is Sterling Health. Despite the fact that paracetamol is currently produced by many pharmaceutical companies under various names (Acetaminophen, Watsou, USA; Dolipran, USA-France; Miralgan, Yugoslavia; Calpol, Wellcome England; Dofalgan, France, etc.), certain conditions are required to obtain a pure product. Otherwise, the drug will contain phenacetin and 4-p-aminophenol. It was these toxic components that did not allow paracetamol to take its rightful place in the medical arsenal of doctors for a long time. Paracetamol (Panadol) is produced by Western firms, in particular by Sterling Health, under GMP conditions and contains a highly purified active ingredient.

MECHANISM OF ACTION OF PARACETAMOL.

It has been established that paracetamol is a weak inhibitor of prostaglandin biosynthesis, and its blocking effect on the synthesis of prostaglandins - mediators of pain and temperature reaction - occurs to a greater extent in the central nervous system than in the periphery. This explains the presence of a pronounced analgesic and antipyretic effect of paracetamol and a very weak anti-inflammatory effect. Paracetamol practically does not bind to plasma proteins, easily penetrates the blood-brain barrier, and is almost evenly distributed in the brain. The drug begins a rapid antipyretic and analgesic effect after about 20-30 minutes and continues to act for 4 hours. The period of complete elimination of the drug is on average 4.5 hours.

The drug is mainly excreted by the kidneys (98%), the main part of the administered dose is biotransformed in the liver. Due to the fact that paracetamol has practically no effect on the gastric mucosa, i.e., does not cause an ulcerogenic effect. This also explains the absence of bronchospasm when using paracetamol, even in people suffering from bronchial asthma. The drug does not affect, unlike aspirin, the hematopoietic system and the blood coagulation system.

These advantages, as well as the wide breadth of the therapeutic action of paracetamol, have now allowed it to take its rightful place among other non-narcotic analgesics. Preparations containing paracetamol are used for the following indications:

1) Pain syndrome of low and medium intensity of various origins (headache, toothache, neuralgia, myalgia, pain in injuries, burns).

2) Febrile fever in infectious and inflammatory diseases. It is most good as an antipyretic in pediatric practice, in pediatrics.

Sometimes aniline derivatives (phenacetin, for example) are combined in one tablet with other non-narcotic analgesics, thus obtaining combined drugs. Most often, phenacetin is combined with AA and codeine. The following combined preparations are known: asphene, sedalgin, citramon, pircofen, panadein, solpadein.

Side effects are few and more due to the administration of phenacetin than paracetamol. Reports of serious adverse reactions to paracetamol are rare and are usually associated with either drug overdose (greater than 4.0 per day) or prolonged (greater than 4 days) use of the drug. Only a few cases of thrombocytopenia and hemolytic anemia associated with taking the drug have been described. The most frequently reported development of methemoglobinemia with the use of phenacetin, as well as a hepatotoxic effect.

As a rule, modern non-narcotic analgesics have, first of all, a pronounced anti-inflammatory effect, therefore they are most often called NSAIDs.

These are chemical compounds of various groups, mainly salts of various acids:

a) derivatives acetic acid: indomethacin, sulindac, ibufenac, sofenac, pranoprofen;

b) propionic acid derivatives: ibuprofen, naproxen, ketoprofen, surgam, etc.;

c) anthranilic acid derivatives: flufenamic acid, mefenanic acid, voltaren;

d) derivatives nicotinic acid: niflumic acid, clonixin;

e) oxicams (enolinic acids): piroxicam, isoxicam, sudoxcam.

Indomethacin (Indomethacinum; capsules and dragees at 0.025; suppositories - 0.05) is a non-steroidal anti-inflammatory drug (NSAID), which is a derivative of indoleacetic acid (indole). It has anti-inflammatory, analgesic and antipyretic activity. It is one of the strongest NSAIDs and is the reference NSAID. NSAIDs - unlike salicylates, cause reversible inhibition of prostaglandin synthetase (COX).

Its anti-inflammatory effect is used in exudative forms of inflammation, rheumatism, disseminated (systemic) connective tissue diseases (SLE, scleroderma, periarthritis nodosa, dermatomyositis). The drug is best for inflammatory process accompanied by degenerative changes in the joints of the spine, with deforming osteoarthritis, with psoriatic arthropathy. Used in chronic glomerulonephritis. Very effective in acute attacks of gout, analgesic effect lasts for 2 hours.

In premature babies, it is used (1-2 times) to close the functioning arterial ductus arteriosus.

It is toxic, therefore, in 25-50% of cases, pronounced side effects occur (cerebral: headache, dizziness, tinnitus, confusion, blurred visual perceptions, depression; from the gastrointestinal tract: ulcers, nausea, vomiting, dyspepsia; skin: rashes; blood: dyscrasia; sodium ion retention; hepatotoxic). Children under 14 are not recommended.

The next NSAID - IBUPROFEN (Ibuprofenum; in Table 0, 2) - was synthesized in 1976 in England. Ibuprofen is a derivative of phenylpropionic acid. In terms of anti-inflammatory activity, analgesic and antipyretic effect, it is close to salicylates and even more active. Well absorbed from the gastrointestinal tract. Better tolerated by patients than AA. When taken orally, the frequency is lower adverse reactions. However, it also irritates the gastrointestinal tract (up to an ulcer). In addition, with an allergy to penicillin - patients will be sensitive to brufen (ibuprofen), especially patients with SLE.

For 92-99% binds to plasma proteins. It slowly penetrates into the joint cavity, but lingers in the synovial tissue, creating higher concentrations in it than in the blood plasma and slowly disappearing from it after cancellation. It is quickly excreted from the body (T 1/2 = 2-2.5 hours), and therefore frequent administration of the drug is necessary (3-4 times a day - the first dose before meals, and the rest after meals, to prolong the effect).

It is indicated for: treatment of patients with RA, deforming osteoarthritis, ankylosing spondylitis, rheumatism. It gives the greatest effect in the initial stage of the disease. In addition, ibuprofen is used as a strong antipyretic.

A drug close to brufen is NAPROXEN (naprosin; tab. 0, 25) is a derivative of naphthylpropionic acid. Rapidly absorbed from the gastrointestinal tract, the maximum concentration in the blood after 2 hours. 97-98% bound to plasma proteins. Penetrates well into tissues synovial fluid. It has a good analgesic effect. The anti-inflammatory effect is approximately the same as that of butadione (even higher). The antipyretic effect is higher than that of aspirin, butadione. It has a long-term effect, so it is prescribed only 2 times a day. Well tolerated by patients.

Apply it:

1) as an antipyretic; in this regard, it is more effective than aspirin;

2) as an anti-inflammatory and analgesic agent in RA, chronic rheumatic diseases, with myositis.

Adverse reactions are rare, realized in the form of dyspeptic symptoms (heartburn, abdominal pain), headache, sweating, allergic reactions.

The next modern NSAID is SURGAM or thioprofenic acid (Tables 0, 1 and 0, 3) is a derivative of propionic acid. It has analgesic and anti-inflammatory effects. The antipyretic effect of the drug was also noted. Same indications and side effects.

DICLOFENAC-SODIUM (Voltaren, Ortofen) is a derivative of phenylacetic acid. Today it is one of the most active anti-inflammatory drugs, in terms of strength it is approximately equal to indomethacin. In addition, it has a pronounced analgesic, as well as antipyretic effect. According to the anti-inflammatory and analgesic effect, it is more active than aspirin, butadione, ibuprofen.

It is well absorbed in the gastrointestinal tract, when taken by mouth, the maximum concentration in the blood occurs after 2-4 hours. Intensively undergoes presystemic elimination, and only 60% of the accepted dose enters the circulatory system. 99% bound to plasma proteins. Quickly penetrates into the synovial fluid.

It has low toxicity, but a significant breadth of therapeutic action. Well tolerated, sometimes only causing dyspeptic and allergic reactions.

It is indicated for inflammation of any localization and etiology, but it is mainly used for rheumatism, RA and other connective tissue diseases (with Bechterew's disease).

PIROXICAM (izoxicam, sudoxicam) is a new non-steroidal anti-inflammatory drug that differs from other NSAIDs, a derivative of oxicam.

Satisfactorily absorbed from the gastrointestinal tract. The maximum concentration in the blood occurs after 2-3 hours. When taken orally, it is well absorbed, its half-life is about 38-45 hours (this is with short-term use, and with long-term use - up to 70 hours), so it can be used once a day.

SIDE EFFECTS: dyspepsia, occasionally hemorrhages.

Piroxicam inhibits the formation of interleukin-1, which stimulates the proliferation of synovial cells and their production of neutral proteolytic enzymes (collagenase, elastase) and prostaglandin E. IL-1 activates the proliferation of T-lymphocytes, fibroblasts and synovial cells.

In plasma, it is 99% bound to proteins. In patients with rheumatoid arthritis, it penetrates well into the synovial fluid. Doses of 10 to 20 mg (1 or 2 tablets) cause analgesic (30 minutes after ingestion) and antipyretic effects, and higher doses (20-40 mg) - anti-inflammatory (by the end of 1 week of continuous use). Unlike aspirin, it is less irritating to the gastrointestinal tract.

The drug is used for RA, ankylosing spondylitis, osteoarthritis and exacerbation of gout.

All of the above agents, with the exception of salicylates, have a more pronounced anti-inflammatory effect than other agents.

They well suppress exudative inflammation and the accompanying pain syndrome and significantly less actively affect the alterative and proliferative phases.

These drugs are better tolerated by patients than aspirin and salicylates, indomethacin, butadione. This is why these drugs have been mainly used as anti-inflammatory drugs. Hence they got the name - NSAIDs (non-steroidal anti-inflammatory drugs). However, in addition to these new NSAIDs, non-steroidal PVAs by and large now also include old drugs - non-narcotic analgesics.

All new NSAIDs are less toxic than salicylates and indomethacin.

Not only do NSAIDs not have an inhibitory effect on destructive processes in cartilage and bone tissues, but in some cases they can even provoke them. They disrupt the ability of chondrocytes to synthesize protease inhibitors (collagenase, elastase) and thereby increase cartilage and bone damage. By inhibiting the synthesis of prostaglandins, NSAIDs inhibit the synthesis of glycoproteins, glycosaminoglycans, collagen and other proteins necessary for cartilage regeneration. Fortunately, deterioration is observed only in some patients, while in the majority, limiting inflammation can prevent further development of the pathological process.

LECTION lecture No. 9 109

ANALGESIATORS.

Lecture plan.

22. Analgesics (definition, classification, comparative characteristics of drug groups).

23. Narcotic analgesics: definition, classification (taking into account the effect on opiate receptors), mechanism of action.

22. Comparative characteristics groups of analgesics.

22. Pharmacological characteristics of non-narcotic analgesics (analgesics-antipyretics), application.

23. Nociceptive and antinociceptive systems, their relationship.

23. Narcotic analgesics: definition, class and fication (taking into account the effect on opiate receptors), mechanism of action, comparative characteristics, application.

23. Medico-biological and social problems of opium addiction.

23. Acute morphine poisoning (clinic, drug assistance).

Lecture EECTION No. 109 10

Analgesics.

The nociceptive system is the system that sends pain sensations to the brain. Pain messages travel to the brain via two different pathways (Figure 10.1).

The first route of pain transmission(red): These are myelinated fast-conducting thick fibers. Their activation gives a feeling acute pain. These fibers (the "fast track") travel from pain receptors directly to the thalamus. and further Then to the sensory and motor areas of the posterior central gyrus of the cerebral cortex. This system performs a warning function. It immediately delivers information to the brain about the damage, its size and location. She answers the question “where does it hurt?”

The second route of pain transmission(blue): Myelin-free slow-conducting fibers. When they are excited, diffuse aching pain occurs. These fibers ("slow path") go from pain receptors to the reticular formation, hypothalamus, thalamus and limbic system. They end in the superior frontal and parietal gyrus of the cerebral cortex. The presence of a large number of synapses, the absence of a myelin sheath and a smaller thickness of the fibers slow down the passage of impulses along this path. This system allows a person who has been injured to attribute certain qualities to his sensations. She answers the question: "How does it hurt"?

Pain is transmitted by: acetylcholine, norepinephrine, dopamine, serotonin, and substance R.

23. Antinociceptive system.

This is a system that inhibits the flow of pain sensations to the brain.

23. The relationship of nociceptive and antinociceptive systems.

On the bodies of neurons, the nociceptive system that transmits pain, there are synapses with other neurons. These are the neurons of the antinociceptive system, which follows it like a shadow. They distinguish 3 types of mediators, each of which consists of 5 amino acids: 1) endorphin-;, 2) enkephalin-;, 3) dynorphin. Each of them predominantly excites its own opioid receptors on the bodies of neurons of the nociceptive system: 1) endorphin mu, 2) enkephalin - delta, and 3) 3) dynorphin - kappa opioid receptor. Excitation of opioid receptors causes pharmacological effects (Fig. 10.2).

22. Definition.

22. Classification.

1. Narcotic (opioid) and 2) non-narcotic (non-opioid) analgesics.

22. Opioid analgesics.

22. Definition.

These are substances capable of suppressing intracentral conduction and perception of pain during a resorptive action, and upon repeated use, cause mental and physical dependence (morphinism).

23. Classification(Fig. 10.3).

Morphine

Heroin

Metadoin

meperidine

Trimeperidine

Fentanyl

Sufentanil

Codeine

propoxyphene

Buprenorfic

Pentazocine

Tramadol

Naloxone

Natrexone

Figure 10.3 Opioid analgesics and antagonists.

22. Analgesics.

22. Definition.

Analgesics are drugs that selectively suppress pain sensitivity during resorptive action without turning off consciousness and without inhibiting other types of sensitivity.

tichesk

tic.N).

22. Narcotic opioid analgesics.

ee

23. Classification of narcotic (opioid) analgesics(taking into account the effect on opiate receptors) (Fig. 10.3).

1. They cause hyperpolarization and inhibition of neurons of the nociceptive system due to the exit from them K + .

2. Reduce intake of C a ++ into presynaptic nerve endings of neurons of the nociceptive system. C, thereby reducing the release of the neurotransmitter into the synapse.

opioid receptors.

Serpentine. Paired with G -protein. Exogenous opioids mimic the action of endogenous ones. Vopiopeptins and cause effects depending on the type of opioid receptors they excite (Fig. 10.4).

Non-narcotic (non-opioid) analgesics. These are substances that exhibit a moderate analgesic effect mainly at the pathogenetic level, blocking the formation and action on pain endings of tissue “algogenic” substances that are formed during inflammation, ischemia and tissue trauma.

22. Comparative characteristics of drug groups(Fig. 10.1).

2 3. Nociceptive and antinociceptive systems.

The nociceptive system is the system that sends pain sensations to the brain. Pain messages travel to the brain via two different pathways (Figure 10.2).

The first route of pain transmission:these are myelinated fast-conducting thick fibers, their activation gives a sensation of acute pain. These fibers (the “fast track”) travel from the pain centers directly to the thalamus and on to the sensory and motor areas of the posterior central gyrus of the cerebral cortex. This system performs a warning function, it immediately delivers information about the damage, its size and localization. She answers the question" Where does it hurt ?"

The second way of pain transmission:unmyelinated slow conducting fibers. When they are excited, diffuse aching pain occurs. These fibers ("slow path") go from pain receptors to the reticular formation, hypothalamus, thalamus, limbic system. They end in the superior frontal and parietal gyrus of the cerebral cortex. The presence of a large number of synapses, the absence of a myelin sheath and a smaller thickness of the fibers slow down the passage of impulses along this path. This system allows a person who has been injured to attribute certain qualities to his sensations. She answers the question: "How does it hurt"? Pain is transmitted by: acetylcholine, norepinephrine, dopamine, serotonin, and substance R.

23. Antinociceptive system. This is a system that inhibits the flow of pain sensations to the brain.

23. The relationship of polyceptive and antinociceptive systems.

On the bodies of neurons, nociceptive, transmitting a feeling of pain, there are synapses with other neurons. These are the neurons of the antinociceptive system, which follows it like a shadow. They distinguish 3 types of mediators, each of which consists of 5 amino acids: 1) endorphin; 2) enkephalin; 3) dynorphin. Each of them predominantly excites its own opioid receptor: 1) endorphin MU, 2) enkephalin-delta, and 3) dynorphin-kappa opioid solution. Excitation of opioid receptors causes effects (Fig. 4).

In people with insufficient production of opiopeptins, a slight blow or scratch causes severe pain. The largest number opiopeptins are released in the region of the central periaqueductal substance. They inhibit the conduction of pain impulses in the central nervous system.

23. Narcotic (opioid) analgesics.

23. Definition.

Opioid analgesics are drugs that, with a resorptive effect, suppress intracentral conduction and perception of pain, and upon repeated use, cause mental and physical dependence (morphinism).

23. Classification of narcotic (opioid) analgesics(taking into account the effect on opiate receptors) (Fig. 10.5).

23. Mechanism of action of opioid analgesics.

1. Cause hyperpolarization and inhibition of neurons of the nociceptive system due to the exit from them K + .
2. Reduce output C a ++ into presynaptic nerve endings and thereby reducing transmitter release. Serpentine opioid receptors are associated with G -proteins. Exogenous opioids mimic the action of endogenous opiopeptins on the type of opioid receptors they excite (Figure 4).

23. Comparative characteristics and use of opioid analgesics.

Strong agonists.

They have a high affinity for mu receptors and a different, lower affinity for delta and kappa receptors.

Influence on the central nervous system.

These are: 1) analgesia,; 2) euphoria,; 3) lethargy;; 4) respiratory depression, 5) cough suppression, 6) miosis, 7) nausea and vomiting, 8) bradycardia. With repeated administration, a pronounced tolerance to these effects develops.

1. Analgesia. Patients receiving strong agonists do not feel pain, but sensitivity is preserved. That is, pain is perceived as something pleasant.

2. Euphoria . The pain patient or addict experiences great satisfaction and well-being after administration of strong agonists. Disappear anxiety and discomfort. Euphoria is due to stimulation of the ventral tegmentum.

3. Lethargy. Manifested by drowsiness, clouding of consciousness, impaired ability to reason. Sleep develops more often in young people healthy people than in the elderly. He's not deep. The combination of strong agonists with sedative and hypnotic hypnotic drugs potentiates their action. Has a more pronounced sedative effect morphine . and to a lesser extent - synthetic substances mmeperidine and, fentanyl.

4. Respiratory depression. Dose-dependent.s Until the stop. mMechanism: the sensitivity of neurons of the respiratory center to CO decreases 2 . As a result of respiratory depression, CO accumulates in the blood 2 . This leads to the expansion and decrease in the resistance of the cerebral vessels. Increased cerebral blood flow and intracranial pressure. That's why morphine contraindicated in people with severe brain damage.

Note. Respiratory depression is the cause of death in acute opioid overdose.

5. Cough suppression.Does not correlate with analgesic effect and respiratory depression. The receptors involved in antitussive action are different from those involved in analgesia.

Cough suppression with cough opioids can lead to accumulation of secretions with subsequent obstruction. respiratory tract and atelectasis. Tolerance develops to this effect.

6) MiosisMiosis (sS ). Opioids excite the nuclei oculomotor nerves. Increased parasympathetic stimulation of the eyes. Tolerance does not develop. All drug addicts find out the state of the pupil.

Note . This is an important diagnostic technique. In most other cases of coma and respiratory depression, mydriasis develops. Miosis is eliminated by atropine and an antagonist.

7.8. Nausea and vomiting.Opioid analgesics activate the brainstem chemoreceptor trigger zone and can cause nausea and vomiting. Stimulate the vestibular apparatus. Nausea and vomiting are aggravated by movement. Vomiting does not cause discomfort.

Note. The vomiting center is oppressed.

8. Bradycardia . A consequence of stimulation of the nuclei of the vagus nerves.

Neuroendocrine effects. Strong agonists inhibit the release of gonadotropin and corticotropin releasing hormones. Reduce the concentration of: luteinizing, follicle-stimulating, adrenocorticotropic hormones and beta-endorphins; testosterone and cortisol. They increase the release of prolactin and growth hormone by weakening their dopaminergic inhibitory effect.

peripheral effects.

Rigidity of the muscles of the body. Strong agonists increase skeletal muscle tone. The action develops at the spinal level. The effectiveness of the work of the pectoral muscles decreases. Decreased pulmonary ventilation. The effect is most pronounced with rapid intravenous administration of large doses of lipophilic opioids ( fentanyl, sufentanil ). Eliminated by opioid antagonists. is becoming more frequent CO 2

gastrointestinal tract . Constipation. Opioid receptors have a high density in the gastrointestinal tract. Mechanism. The release of acetylcholine in the gastrointestinal tract is blocked.

Urogenital system.Opioids reduce the intensity of blood flow to the kidneys and reduce their function. The tone of the ureters and bladder increases. An increase in the tone of the urethral sphincter leads to urinary retention, especially in the postoperative period.

Uterus . Opioid analgesics prolong labor.if

Other effects . Opioid analgesics cause reddening of the skin and a feeling of warmth due to (vasodilatation), and sometimes combined with sweating and urticaria. These reactions are associated with:

central effects and;

release of histamine from mast cells.

Tolerance and physical dependence.

With frequently repeated administrations in therapeutic doses morphine and its analogues develops tolerance. To obtain a response equal to the original, you have to increase the dose. From this period, physical dependence is formed. It becomes necessary to continue the administration of the substance to prevent the occurrence of a withdrawal or withdrawal syndrome.

Mechanisms for the development of tolerance and physical dependence:

1) :

changing the system of secondary intermediaries; 2)

inhibition of adenylate cyclase; 3)

synthesis of G-proteins.

The degree of tolerance to some effects of opioids Fig. .10.5).

Opioid analgesics cross the placenta. Their use for pain relief in obstetrics can lead to the birth of a child with depressed breathing.

Newborns born to mothers who are drug addicts are characterized by physical dependence with symptoms of opioid withdrawal if they do not enter their body.

Characteristics of drugs.

Morphine . Effective in the treatment of severe pain syndrome.

Application.

Anesthesia. Causes pain relief and sleep. This is important, especially in intensive care after surgery. Can be used as an adjunct to sleeping pills when pain is reduced.

Diarrhea treatment. Morphine reduces the contractility of the smooth muscles of the intestine and increases its tone. Used for cholera.

Cough relief. Morphine suppresses the cough reflex. Chs; however, more commonly used codeine or dextromethorphan.

Side effect.Severe respiratory depression, vomiting, dystrophyaphoria, hypotension. Raises

Increased intracranial pressure. This leads to ischemia of the brain and spinal cord. With prostatic hypertrophy, it can cause acute urinary retention. Serious complication Respiratory depression in emphysema and in patients with pulmonary heart disease.

Heroin.

Receipt. (Fig. 6).

Heroin. Not found in nature. Obtained by acetylation morphine in the position indicated by the dot (Fig. 10.6).

Action. 3 times stronger than morphine. Causes pronounced epharia.

Pharmacokinetics.

This Heroin is more fat soluble. Faster morphine crosses the blood-brain barrier. In the brain it turns into morphine . causing pronounced euphoria while causing pronounced euphoria Application . Not used in medicine.

Methadone . Synthetic oral opioid. . W. Longer

Mechanism of action. Methadone predominantly excites mu-receptors. It has a pronounced effect on myo-receptors.

Action. Pain relieving activity methadone is equivalent to morphine . It has a strong analgesic effect when taken by mouth.

Note. Morphine , partially absorbed from the gastrointestinal tract. Pupil constriction and respiratory depression methadone last 24 hours. Increases pressure in bile ducts and causes constipation. Euphoria is less pronounced than that of morphine.

Pharmacokinetics.

Methadone well absorbed when taken by mouth.

Application. 1. To control withdrawal symptoms in heroin and morphine addicts. 2. For the treatment of drug addicts. Patients are then slowly removed from methadone dependence.

Note. Methadone causes moderate withdrawal syndromes. It proceeds not so hard that develop,. It is easier to carry. than withdrawal syndromes morphine.

Side effect. Addiction. Withdrawal syndromes are expressed in an average degree and longer (from days to weeks).

Meperidine. With meperidine Synthetic opioid for oral and parenteral administration.

Mechanism of action. Opioid receptor agonist, especially kappa.

Action.

Breath. Oppression. breathing like morphine.

The cardiovascular system.Slight effect when taken by mouth. When administered intravenously, it causes: 1) a decrease in peripheral vascular resistance and 2) an increase in peripheral blood flow; 32) tachycardia. The latter due to antimuscarinic properties. It has a negative inotropic effect. Expands the vessels of the brain and increases the pressure of the cerebrospinal fluid.

GIT. meperidine reduces smooth muscle. Leads to constipation.

Eye . Meperidine, as opposed to morphine , causes pupil dilation.

Application . meperidine causes pain relief in severe pain. Unlike morphine not used for diarrhea or cough. Causes less urinary retention than morphine.

Side effect. Large doses of meperidine cause trembling, muscle twitching and convulsions. It differs from other opioids in that it dilates the pupil at high doses and causes excessive reflexes. meperidine drug. Replace morphine and heroin when used by addicts. In patients with renal insufficiency, its metabolite, normeperidine, accumulates. Seizures develop.

Fentanyl subgroup fentanyl, sufentanil and alfentanil.

Trimeperidine (promedol).

Action . Strong analgesic. with the introduction of anesthetics Weaker morphine depresses respiration, nuclei of the vagus nerve and the vomiting center. Antispasmodic, but stimulates the uterus.

Pharmacokinetics.

Absorbed quickly. Effective when taken orally and parenterally.

Interaction . Enhances the effect of local anesthetics.

Fentanyl.

Action. The strength of the analgesic effect is 80 times greater than morphine.

Pharmacokinetics.

It has a fast onset and a short (15-30 minutes) duration of action.

Interaction. In combination with droperidol it causes uncoupled anesthesia (neuroleptanalgesia).

Sufentanil. Action. вВ 5-7 times more active fentanyl.

moderate agonists.

Codeine. Action. Weaker than morphine . However, when taken orally codeine more effective morphine.

Application. Rarely used alone. More often in combined dosage forms with aspirin, paracetamol and other NSAIDs. It has a good antitussive effect in doses that do not eliminate pain. The analgesic effect is equivalent aspirin.

Side effects. Codeine causes less euphoria than morphine . Rarely causes addiction. [Note:. B To eliminate cough instead of use codeine dextromethorphan. This synthetic substance has no analgesic effect. Has low addiction potential].

Weak agonists.

propoxyphene.

Action. Methadone derivative . When parenterally applied, it causes pain relief, which is 2 times weaker than that of codeine . When taken orally, its activity is only 1/3 that of codeine.

Pharmacokinetics.Well absorbed after oral administration with peak plasma levels after 1 hour. Metabolized in the liver.

Application . In combination with aspirin to enhance the analgesic effect.

Side effects.through nausea, aporexia, constipation.

Overdose . Lethargy, respiratory depression, convulsions, hallucinations. Cardiotoxicity and pulmonary edema.

Help with overdose. Naloxone . Eliminates lethargy and respiratory depression, but not cardiotoxicity. At

Interaction . With alcohol and sedatives. Severe CNS depression develops, leading to death from respiratory depression and cardiotoxicity.

Partial agonists.

Buprenorphine . Active and long-acting opioid. Partial mu receptor agonist.

Action. Long. action due to strong binding to mu receptors.

Note. Used for detoxification and maintenance treatment of heroin addicts.

Agonists-antagonists.(Fig. 10.7).

Mechanism of action.SOpioids, which stimulate some but block other receptors (Fig. 10.7).

Action. called agonist-antagonist. In people who have recently received opioids, agonist-antagonists have an agonistic effect. Is elimination In patients with dependence on opioids, they have an antagonistic effect. Oh, exacerbate withdrawal symptoms. They cause not more dystrophy than euphoria, but dysphoria (bad mood).

Note. Pain syndrome.

Characteristics of drugs..

Pentozocin.

Mechanism of action.Agonist of kappa-, and delta- and c Weak Possesses weak antagonistic activity to mu- and delta-receptors. IueliminationApply

Action. Euphoria, less pronounced than that of morphine.

Pharmacokinetics.Apply by mouth and parenterally.

Note. Moderate pain. To reduce symptoms of morphine addiction.

Side effects.In large doses, it inhibits respiration and gastrointestinal motility. Boosts boosts blood pressure. May and may Causes hallucinations, nightmares and dizziness. With angina pectoris pentazocine increases pressure in the aorta and pulmonary artery. Therefore, and therefore increases the load on the heart. Reduces blood flow in the kidneys.

Interaction. With morphine. Does not relieve respiratory depression. Can symptoms

Tramadol.

Note. Strong analgesic.

Pharmacokinetics. Assign inside and parenterally. Acts quickly and for a long time.

Note Introduction Application. Strong pains. Especially in cancer patients.

Partial agonists.

Buprenorphine An active and long-acting opioid. Mu receptor partial agonist. Long-term action due to strong binding to mu-receptors, which makes it resistant to elimination naloxone . Used in detoxification and maintenance treatment of heroin addicts.

Antagonists.

Structure. Morphine derivatives with bulky substituents at the nitrogen atom (see Fig. 10.7).

Mechanism of action.Blockade of opioid receptors, especially with mui block them.

Action. elicit a receptor-mediated response. Normal people don't work. Addicts quickly lead to the cessation of heroin. Withdrawal syndrome develops. Mechanism: displace heroin from the receptor.

Characteristics of drugs.(See Figure 10.7).

Naloxone.

Mechanism of action.Competitive opioid antagonist. Quickly displaces them from the receptors. Blocks the receptor (Figure 10.7). receptors.

Application . Opioid overdose. (Figure 10.7).

Within 30 seconds after intravenous administration naloxone the respiratory depression and coma characteristic of a heroin overdose disappear. Consciousness returns, appears bringing the patients to their senses and alertness. Naloxone competitive opioid receptor antagonist.

Naltrexone. See naloxone.

Action . Lasts longer on the loxon. like naloxone . Has a longer duration of action than naloxone . With a single ingestion, it blocks the action of injected heroin for 48 hours. [Note. Tolerance and withdrawal syndrome to naltrexone and naloxone does not develop].

Application. June 1. Naltrexone is used to create opiate-dependent maintenance programs for the treatment of drug addicts. In opioid dependent patients who appear normal on the outside naltrexone causes withdrawal syndrome. 2. With prolonged use, the syndrome does not develop NS reduces cravings for alcohol in chronic alcoholics.

23. Medico-biological problems of opium addiction.

1. Risk of fatal overdose. 2.

Polydrug addiction. Alcohol, sedatives and stimulant substitutes for opioids. 3.

Hepatitis B. 4.

AIDS. 5.

Bacterial infections with septic complications (meningitis, osteomyelitis, abscesses in the internal organs).

23. Social problems opium addiction.

Murders, suicides, accidents, public spending on drug treatment, family breakdown.

23. Acute morphine poisoning: clinic.

Euphoria, anxiety, sensation of heat, dry mouth, dizziness, headache, sweating, urge to urinate, drowsiness, stupor, coma. Rare (3-5 breaths per minute) and shallow breathing. Decreased blood pressure, pinpoint sharply constricted pupils. ([Note: As hypoxia progresses, the pupils dilate]). P; elevated spinal reflexes, hypothermia,. With death as a result of paralysis of the respiratory center.

23. Drug help. Naloxone by vein.

Use of opioids (summary)..

Morphine . Pain, diarrhea with cholera, cough with broken ribs.

Heroin. Not Not applicable.

Methadone . To control withdrawal symptoms in drug addicts.

meperidine . Trimeperidine. Pain..

Fentanyl. For compartmental anesthesia (with droperide o scrap).

Sufentanil. Pain.

Codeine. Cough.

propoxyphene . With NPFS at pains of an inflammatory origin.

Buprenorphine and pentazocine. Treatment of heroin addicts.

Tramadol . Pain in cancer patients.

Naloxone . With an overdose of opioids (coma, respiratory depression). i). To reduce cravings for alcohol.

Naltrexone . To reduce cravings for alcohol.

22. Non-narcotic pioid analgesics.

Definition. These are substances that exhibit a moderate analgesic effect, mainly at the pathogenetic level, blocking the formation and effect on the pain endings of tissue “ algogenic ”substances that are formed when:1) inflammation, 2) ischemia and 3) tissue trauma.

22. Pharmacological characteristics of non-opioid analgesics (analgesics-antipyretics), application.

e. Do not relieve pain and but reduce body temperature (analgesics-antipyretics). analgesics because they do not cause physical dependence.

These are non-steroidal anti-inflammatory drugs with little or no anti-inflammatory activity. (Fig. 10.2).

Classification (Figure 10.8).

Analgesic effect.

To a large extent, it manifests itself with pains of low and moderate intensity emanating from tissues of ectodermal origin (muscles, joints, tendons, nerve trunks, central nervous system, teeth). With severe visceral pain, they are not very effective. [Note. metamizole and ketorolac effective for colic and postoperative pain. Their effectiveness in renal colic is associated with inhibition of the formation of prostaglandin E. 2 in the kidneys by inhibiting cyclooxygenase. Decreased renal blood flow and urine production. This leads to a decrease in pressure in the renal pelvis and ureters above the site of obstruction. Provides long lasting pain relief] . The blockade of the conversion of arachidonic acid into prostaglandins by unexpected non-opioid analgesics is the main one in their analgesic activity for pains of various localization. [Note. Prostaglandins cause pain by sensitization of receptors to pain mediators (histamine, bradykinin) and mechanical action, lowering the threshold of pain sensitivity].

In addition, the analgesic effect of non-opioid analgesics is associated with impaired conduction of pain impulses in the spinal cord.

Antipyretic effect.

Reduce body temperature only with fever. Normal temperature is not affected.

Antipyretic mechanism.

Prostaglandin E 2 increases the sensitivity of the hypothalamic centers of thermoregulation to the action of endogenous pyrogens (interleukin 1 and others) formed in the body under the influence of microorganisms, viruses and toxins. Blocking the synthesis of prostaglandin E 2 they lower the body temperature.

Application.

Rheumatism; rheumatoid, gouty and psoriatic arthritis; ankylosing spondylitis, Reiter's syndrome. [Note. Reiter's syndrome is urethritis + iridocyclitis + arthritis → urethrooculosynovial syndrome]. In rheumatoid arthritis, they have only a symptomatic effect. Do not affect the course of the disease. They cannot stop the progression of the process, cause remission and prevent the development of joint deformity. But the relief that non-opioid analgesics bring to patients with rheumatoid arthritis is so significant that patients cannot do without them.

2. Non-rheumatic diseases of the musculoskeletal system (osteoarthritis, myositis, tendovaginitis, trauma). More often locally (ointments, creams, gels).

3.2. Neuralgia, sciatica, sciatica, lumbago.

43 Renal and hepatic colic.

45 Pain syndrome of various etiologies, including headache and toothache, postoperative pain.

56 Fever (usually (at a temperature above 38.5 FROM ) .

67 Dysmenorrhea. Used for primary dysmenorrhea to relieve pain associated with increased uterine tone due to hyperproduction of prostaglandin F 2a . In addition to the analgesic effect, they reduce the amount of blood loss. Assign at the first appearance of pain in a 3-day course or on the eve of menstruation. With such a short-term treatment, their side effects do not develop.

Contraindications.

Non-opioid analgesics are contraindicated in erosive and ulcerative lesions of the gastrointestinal tract (especially in the acute stage), severe violations of the liver and kidneys, bone marrow, cytopenias, individual intolerance, pregnancy.

Precautions.

Non-opioid analgesics should be used with caution in patients with bronchial asthma, as well as in people who have previously recorded side effects when taking NSAIDs.

Elderly patients are prescribed minimally effective doses in short courses.

Side effect.

GI tract. Dispep c ic disorders. Erosions, ulcers of the stomach and duodenum. Bleeding and perforation of the gastrointestinal tract.

Mechanisms of the gastrointestinal toxicity:1) inhibition of the activity of cyclooxygenase-1 (COX-1), which controls the production of prostaglandins that regulate the integrity of the gastrointestinal mucosa (the main mechanism); 2) local damage to the mucosa by non-opioid analgesics, since most of them are organic acids.

COX-1 blockade is the result of the systemic action of non-opioid analgesics. Causes gastrotoxicity in any route of administration.

The defeat of the gastric mucosa with non-opioid analgesics proceeds in 3 stages: 1) inhibition of the synthesis of prostaglandins in the mucosa; 22) reduction of prostaglandin-mediated production of protective mucus and bicarbonates; 13) ulceration;. Possibly also

2) local damage by non-opioid analgesics to the mucosa, since most of them are organic acids.

The problem of gastrotoxicity of non-opioid analgesics is complicated by their analgesic effect. Against the background of the absence of pain, a pronounced ulceration of the gastric mucosa is detected.

Kidneys.

Nephrotoxicity. It develops through two mechanisms. 1. Blockade of prostaglandin E synthesis 2 and prostacyclin in the kidneys causes vasoconstriction and deterioration of renal blood flow. Renal ischemia develops. C, glomerular filtration and diuresis decrease. Violations of water and electrolyte metabolism develop: (water retention, edema, hypernatremia, increased blood pressure).

2. Direct damage to the kidney parenchyma with the development of interstitial nephritis (“analgesic nephropathy”). Possible development of severe renal failure.

Hematotoxicity. metamizole and propifinazone can cause aplastic anemia and agranulocytosis.

Coagulopathy. Inhibition of the formation of prothrombin in the liver and platelet aggregation. The result bleeding (often the gastrointestinal tract).

Hypersensitivity reactions (allergies).

Rash, angioedema, anaphylactic shock, Lyell and Stevens-Johnson syndromes. More often (more often cause metamizole and propifinazone).

Bronchospasm. In patients with bronchial asthma.

Mechanism of bronchospasm:

1) allergy ( hypersensitivity);

2) inhibition of the synthesis of prostaglandin E 2 , which is an endogenous bronchodilator;

3) an increase in the synthesis of leukotrienes (bronchoconstrictors).

Prolongation of pregnancy and delay in labor.

due to the fact that prostaglandins E 2 and F 2α stimulate the myometrium. Their synthesis is inhibited.

sInteraction.

With indirect anticoagulants and oral hypoglycemic agents. Strengthening the action of the latter.

Mechanism. 1. Displacement from binding sites on albumin. 2. With hypotensive and diuretic. Weaken action.

3. With diuretics. Nephrotoxicity.

Mechanism. Rice. 24.5

4. With aminoglycoside antibiotics and digoxin. Increased toxicity of the latter.

5. With aluminum-containing antacids ( almagel, maalox) as well as cholestyramine. Decreased absorption of non-opioid analgesics.

6. With sedative and opioid analgesics. Strengthening the analgesic effect.

Characteristics of individual drugs.

Mefenamic acid.

Mechanism of action.Inhibition of prostaglandin biosynthesis.

Action . Analgesic Has analgesic properties.

ContraindicatedPharmacokinetics.Slowly absorbed. Partially metabolized in the liver. T½ - 4 hours.

And Application. Rheumatism : rheumatism, nonspecific infectious polyarthritis, arthralgia, myalgia, neuralgia, headache and toothache.

Side effects. More pronounced than aspirin . More toxic. Assign up to 1 week.

Contraindication. Children.

This is a phenomenon.

Action. Anti-inflammatory and analgesic.

Application . Bursitis: bursitis, tendovaginitis, articular syndrome, myositis, lumbago, sprains, dislocations, bruises.

Metamizole (analgin).

Action. Analgesic, anti-inflammatory, antipyretic, antispasmodic action.

Mechanism of analgesic action.Violation of the conduction of pain impulses in the spinal cord.

Quickly etayayaPharmacokinetics.Absorbed quickly. The maximum concentration in the blood in 1-2 hours, T½ - 2.5 hours.

Application :. Headaches of various genesis (headache, neuralgia, sciatica, rheumatism). For severe pain, it is administered parenterally.

Side effect. G : oppression of hematopoiesis (granulocytopenia, agranulocytosis), allergic reactions, anaphylactic shock(possible with intravenous administration).

Contraindications.: Increased hypersensitivity, hematopoietic disorders.

Propyphenazone.

Action . Pronounced analgesic and antipyretic.Pharmacokinetics.Rapidly absorbed from the gastrointestinal tract. The maximum concentration in the blood in 30 minutes.

Application. Included in the composition of saridon and plivalgin.

Side effects. Safe.

Paracetamol.

One one of the main drugs for the treatment of mild and moderate in cases where there is no need for an anti-inflammatory effect. Weak inhibitor of prostaglandin synthesis in peripheral tissues.

Action . I: paracetamol inhibits the biosynthesis of prostaglandins in the central nervous system. Antipyretic and analgesic action develops. Weakly affects cyclooxygenase in peripheral tissues. Therefore, it has weak anti-inflammatory activity. Does not affect platelet function or prolongs the time of blood clot formation. Deprived of many properties aspirin.

Application . It is effective for (headache, muscle and postpartum pain. In rheumatoid arthritis, it is used as an adjunct to anti-inflammatory therapy for the purpose of analgesia.

Paracetamol good substitute for analgesic and antipyretic action aspirin in patients: 1) with complaints from the gastrointestinal tract, 2) in whom prolongation of bleeding time is not advisable, 3) who do not need anti-inflammatory action aspirin.

Paracetamol the best analgesic and antipyretic in children with viral infection. [Note. Aspirin (recall that aspirin increases the risk of Reye's syndrome)] .

Paracetamol is not an antagonist of the uricosuric agent probenecid and therefore is not contraindicated in patients with gout.

Side effect:.Reddening of the skin and minor allergic reactions occur. There may be minimal disturbances in the content of leukocytes, but they pass. Increased activity of liver enzymes, but without the development of jaundice. The effect is reversible after discontinuation.

Toxicity . Dizziness, agitation and disorientation. Renal tubular necrosis and hypoglycemic coma are rare complications long-term treatment large doses paracetamol.

At doses of 10 g or more, fatal hepatic necrosis may develop in adults due to the depletion of glutathione stores consumed in detoxification reactions. paracetamol . Early symptoms liver damage is nausea, vomiting, diarrhea, abdominal pain. Treatment. - a cetylcysteine (precursor of glutathione). May be life-saving if given within 20 hours of overdose paracetamol . [Note. The prognosis is worse. Early symptoms of liver damage are nausea, vomiting, diarrhea, and abdominal pain. than with an overdose. aspirin].

Hemolytic anemia and methemoglobinemia. Unlike aspirin, paracetamol does not cause gastrointestinal bleeding.

Contraindications.Liver diseases. Yu

Ketorolac.

Action. NSAIDsPotent analgesic Non-steroidal anti-inflammatory drug medium duration actions. Instead of morphine with postoperative pain of mild to moderate severity. Only 2.5 times inferior morphine.

Side effect. Gastrotoxicity and increased bleeding (antiaggregatory effect).

Interactions. with opioid analgesics. Analgesia is potentiated. This allows them to be used in smaller doses.

FROM local anesthetics. Intravenous or intraarticular administration ketorolac with lidocaine or bupivacaine provides better pain relief than separate.

Precautions. Ketorolac should not be used before long-term operations with a high risk of bleeding, as well as for labor pain relief, pain relief in myocardial infarction.

22. Comparative characteristics of opioid and non-opioid analgesics (Fig. 10.9).

Analgesics (Analgetica; from the Greek negative prefixes an- and algos - pain) are neurotropic substances of central action, the main effect of which is the selective suppression of pain sensitivity without inhibiting the sensitivity of other species, without loss of consciousness. The analgesic effect of analgesics is independent of the hypnotic effect inherent in some of them. According to the type of action, analgesics are divided into two groups.
1. Narcotic analgesics (morphine group) include: phenanthrene derivatives - morphine (see), tekodin (see), hydrocodone (see), heroin (not used in the USSR due to toxicity and high ability to cause addiction). Opium and its preparations adjoin here, the main active principle of which is morphine; derivatives of phenylpiperidine - promedol (see), isopromedol, lidol (not used in the USSR, as it is replaced by promedol, which is close in action and has advantages); a derivative of heptanone - phenadone.

2. Non-narcotic analgesics (analgesic and antipyretic) include pyrazole derivatives - amidopyrine (see), analgin (see), antipyrine (see), butadiene (see); aniline derivative - phenacetin (see); salicylic acid derivatives (salicylates) - sodium salicylate, acetylsalicylic acid; tsinhofen, similar in action to salicylates.

Analgesics of the morphine group are the most powerful pain relievers. In appropriate doses, they are able to suppress or dramatically reduce pain of almost any intensity and any origin, including pain associated with diseases. internal organs, which distinguishes them from non-narcotic analgesics. Phenadone has the highest analgesic activity, surpassing morphine and other drugs in this respect by several times. The analgesic effect of analgesic drugs of the morphine group is associated with their inhibitory effect on the afferent systems of the brain. The main role in this is played by dysfunctions of the thalamocortical projection systems, involving the associative and nonspecific nuclei of the thalamus, and their connections with the cerebral cortex. There is a blockage of part of the afferent pathways in the underlying parts of the brain. Simultaneously with pain sensations, analgesics of the morphine group also suppress other negative sensations and emotions caused by physical (fatigue, hunger, fever, etc.) or mental (fear, anxiety, depression) causes, creating a kind of euphoria - a feeling of physical and mental comfort, well-being. This property of analgesics of the morphine group causes the danger of the emergence of a painful addiction to them - drug addiction. Preparations of this group clearly affect the intellectual sphere of a person. At moderate doses, there can be a revival of fantasy and perceptions, facilitating the performance of easy mental work. At the same time, the tension of thought and concentration of attention becomes more difficult, self-control is weakened. At high doses, depression of higher nervous activity develops. All analgesics of the morphine group have a hypnotic effect to some extent, which gives reason to designate this group of substances also by the term narcotic analgesics.

Analgesics of the morphine group have a direct inhibitory effect on the respiratory center, which is expressed primarily in a decrease in breathing. The depth of breathing with moderate doses of analgesics usually does not decrease or only slightly increases, so that pulmonary ventilation does not undergo significant changes. With an increase in doses, as well as as a result of intravenous administration, a decrease in the minute volume of respiration occurs due to a decrease in its depth and a sharp decrease. This property is most pronounced in morphine and fenadone, which makes it undesirable to use them in patients with a threat of respiratory failure and during labor pain relief due to the risk of fetal asphyxia. In such cases, it is preferable to prescribe other analgesics of this group - promedol, tekodin. Analgesics of the morphine group reduce the excitability of the cough center. Under the action of these substances, bradycardia associated with an increase in the tone of the vagus nerves can be observed. This side effect can be eliminated by atropine. A fairly constant central effect is pupillary constriction, which is of diagnostic value in acute and chronic poisoning. Often there is another side effect of the Central - nausea and vomiting.

All analgesics of the morphine group have a pronounced, although unequal, effect on smooth muscles. Phenantrene derivatives increase the contraction of the muscles of the biliary tract, bronchi, uterus, sphincters of the bladder and gastrointestinal tract. The latter, combined with inhibition of the secretion of the digestive glands and a weakening of intestinal motility, leads to constipation. The direct effect of phenylpiperidine derivatives on smooth muscles is to weaken its contractions, which is especially pronounced against the background of spasms (antispasmodic effect). Promedol relaxes the muscles of the cervix during childbirth, causing the acceleration of this act. The direct relaxing effect of phenadone on the smooth muscles of the intestine is usually masked by a centrogenous effect: excitation of the center of the vagus nerves leads to increased peristalsis.

Under conditions of repeated use of narcotic analgesics, the phenomenon of addiction is pronounced, consisting in the development of resistance (tolerance) of the body to the action of these substances. The analgesic and hypnotic effects of the applied dose, respiratory depression and cough center decrease especially quickly. Achieving the initial effect requires a progressive dose increase. There is a phenomenon of cross-addiction: the emergence of tolerance not only to the drug used, but also to other drugs of the same group.

Indications for the use of analgesics of the morphine group are mainly pains of various origins - traumatic, associated with surgical interventions, malignant neoplasms, with diseases accompanied by spasm of smooth muscles (intestinal, renal, hepatic colic), pain syndrome with myocardial infarction, severe neuralgia. The drugs of this group are widely used for pain relief during childbirth and as prenarcotic drugs. They are part of the so-called lytic cocktails. The use of narcotic analgesics before surgery reduces mental stress, anxiety of patients, fear of waiting for pain. These drugs are relatively rarely used to eliminate shortness of breath associated with excessively increased excitability of the respiratory center (cardiac asthma, pulmonary edema), and only in exceptional cases - as an antitussive. In diseases of the intestine (peritonitis, damage to the intestinal wall, some diarrhea), analgesics of the morphine group - mainly opium preparations - are used to reduce intestinal motility. When choosing narcotic analgesics, one should proceed from individual features individual representatives of this group, their relative analgesic activity, the presence by-products actions expressed in different drugs to varying degrees (see individual drug articles). One of the main factors affecting practical use analgesics of this group as a whole, is their inherent ability to cause addiction. In this regard, all narcotic analgesics are dangerous, and the greater the danger, the higher the analgesic activity of the drug. Drug addiction prevention requires the doctor to follow certain rules when prescribing narcotic analgesics. These remedies should be resorted to only in cases where all other measures to eliminate pain are not effective enough. It is necessary to avoid the regularity of giving drugs (at the same hours), striving for the largest possible intervals. It is advisable not to inform the patient about which drug he is receiving. Special instructions for the storage, transport and dispensing of narcotic analgesics must be strictly followed. General contraindications to the use of analgesics of the morphine group are: old age, a state of general exhaustion, respiratory failure. These drugs are not prescribed for children under two years of age.

Acute poisoning with narcotic analgesics is characterized by the development of a coma, collapse and severe respiratory depression, constriction of the pupils, followed by their expansion during asphyxia. Treatment consists in gastric lavage (preferably with the addition of potassium permanganate, activated carbon), the introduction of saline laxatives, the appointment of analeptics (corazol, cordiamine, caffeine, camphor). Of particular value is nalorfin (see) - a physiological antagonist of narcotic analgesics, similar in chemical structure to morphine. Very effective oxygen therapy, artificial respiration. It is recommended to warm the patient, change the position of the body, catheterization of the bladder.

Chronic poisoning with analgesics - see Drug addiction.

Non-narcotic analgesics have a relatively weak (compared to drugs of the morphine group) analgesic activity. In addition, they are effective mainly for muscle, joint, headaches, neuralgia, etc. and are ineffective for pain associated with significant injuries and diseases of the internal organs. The action of the substances of this group is directed, apparently, to the centers of pain sensitivity in the thalamus. Non-narcotic analgesics do not have a hypnotic effect, do not affect the intellectual and emotional spheres and, therefore, do not have a euphoric effect. They are also devoid of all other central effects characteristic of narcotic analgesics and do not affect smooth muscle. Non-narcotic analgesics act on the centers of thermoregulation, as a result of which heat transfer increases and body temperature decreases. This effect when using therapeutic doses is observed only in conditions of fever.

The most widespread practical application is the analgesic effect of non-narcotic analgesics. For achievement best effect often use combined preparations, including several substances of this group, sometimes in combination with barbiturates, caffeine. The use of these analgesics as antipyretics is limited; lowering the temperature with their help is considered appropriate only in cases where febrile phenomena acquire an excessive, dangerous intensity for the body. Salicylates and pyrazole derivatives have antirheumatic and anti-inflammatory properties and are widely used to treat acute articular rheumatism. These drugs, especially butadione, are also effective in the treatment of infectious and gouty arthritis.

With prolonged use of non-narcotic analgesics, especially in large doses, various kinds of side effects may occur: allergic skin reactions, dyspepsia, pain in the stomach, hemorrhages (with the use of salicylates, butadione), hearing loss, tinnitus, hallucinations (from salicylates), methemoglobinemia (from phenacetin). The most dangerous toxic effect - granulocytopenia and agranulocytosis due to bone marrow damage - is sometimes observed with the use of pyrazole derivatives.

When treating with these drugs, medical supervision, blood tests are necessary (when using butadion, every 5-7 days).

Postoperative surgery, migraine attack, malignant tumor or a fracture - unbearable pain can occur due to different reasons. In such a situation, analgin is not enough and folk remedies In order for the pain syndrome to disappear, it is necessary to choose the strongest painkillers.

Pills help with severe pain

Advantages of the tablet form

The advantage of analgesics in tablets over others dosage forms is the ease of use.

Pills are cheaper - the cost of the tablet form of drugs is slightly higher, this pays off by not having to purchase syringes, injection solution and pay for the services of a nurse.

When are painkillers prescribed?

Painkillers are prescribed for people who experience severe pain. Previously, the doctor conducts an examination, the results of the tests help determine what is causing the pain.

Analgesics can be prescribed without examination and testing in case of any surgical intervention, whether it is an appendectomy, reduction of a dislocation or a simple tooth extraction.

Pain syndrome requiring analgesics may occur as a result of the following reasons:

• in the period after the operation;
• with muscle pain, back pain;
• - both in the hands and in the legs;
• with fractures, bruises and severe sprains;
• with oncology;
• with neuralgia;
• (dysmenorrhea).

Antispasmodics and ibuprofen derivatives are prescribed for painful menstruation, and only opioid painkillers help in advanced cancers.

Analgesics used to treat muscle pain

Classification of painkillers

All existing species Analgesics are divided into 2 large groups: these are narcotic and non-narcotic. The first direction, which includes 7 different types, has become more widespread.

Pyrazolones and their combinations

"Simple analgesics" include drugs based on pyrazolones, which include the well-known Analgin. The second name of the group is justified - pyrazolones are really simple and very common on the market, but they do not always help get rid of pain.

Analgin - the most famous analgesic

Combined analgesics

Combined pain relievers combine the properties of several groups of analgesics. The basis of the drugs is paracetamol, combined with other active ingredients. The properties of the combined analgesic are determined by the groups that it combines in itself: analgesic, anti-inflammatory or antispasmodic action.

The basis of combined analgesics is paracetamol.

Antimigraine drugs

NSAIDs are used in the treatment of osteochondrosis

COX-2 inhibitors

The drugs in this group include NSAIDs, but with an important distinctive feature: they do not harm the gastrointestinal tract and, on the contrary, even protect the gastric mucosa. Inhibitors are prescribed for people with peptic ulcers, gastric erosion, and other diseases in which the use of conventional non-steroidal anti-inflammatory drugs is not medically possible.

Inhibitors are prescribed for gastric ulcer

Antispasmodics

The antispasmodic group of painkillers helps to relieve pain by dilating blood vessels and relaxing smooth muscles. Medicines help with spasmodic pains of any nature: during menstruation, migraine or.

Antispasmodics help relieve pain during menstruation

Narcotic analgesics

Opioid, or narcotic analgesics are potent drugs, the appointment of which is justified only in the case of an acute and intolerable pain syndrome. Medicines suppress the transmission of the pain impulse, and the human brain stops perceiving the pain syndrome, filling with euphoria and comfort. Since narcotic analgesics are addictive, they are sold exclusively by prescription, and are prescribed only if painkillers of other groups are ineffective.

List of effective pain pills

The principle of operation of most drugs within the same group is similar, but they can have completely different effects on the body.

In the presented list of painkillers, you can find both expensive and very cheap drugs. Most of these products can be purchased without a prescription at your local pharmacy.

For inflammatory pain

Eliminate head and toothache, severe pain in muscles, bones and joints. They are also effective in painful sensations after trauma and surgery. Non-steroidal anti-inflammatory drugs, as well as analgesics of the combined group, are best for pain syndromes of this nature.

A drug from the group of NSAIDs, created on the basis of ibuprofen. Nurofen is the most popular drug of all non-steroidal anti-inflammatory drugs, the mechanism of action of which is to block the synthesis of prostaglandins, pain mediators that support the inflammatory response in the body. Nurofen helps with any pain of an inflammatory nature, as well as with migraines, dysmenorrhea and neuralgia.

Nurofen copes with inflammatory pain

Contraindications: age under 6 years, 3rd trimester of pregnancy, severe heart failure, gastrointestinal bleeding, kidney failure, ulcer and erosion of the stomach.

Price: 90-130 rubles.

Blue tablets from the NSAID group, used for diseases of the musculoskeletal drug, neuralgia and myalgia, dental and, for tonsillitis, otitis media and fever. Like other nonsteroidal drugs, Nalgesin relieves pain by blocking the synthesis of prostaglandins.

Nalgezin - effective remedy from pain

Contraindications: erosion or gastric ulcer, inflammation in the intestines, renal or hepatic insufficiency, gastrointestinal bleeding, hypersensitivity to the drug, pregnancy and breastfeeding, age under 12 years.

Price: 180-275 rubles.

A combined drug based on paracetamol and ibuprofen, it is used for headaches and toothaches, adnexitis, bursitis, injuries and arthritis, temperature. When taking Ibuklin, pain and fever disappear due to inhibition of cyclooxygenase and a decrease in the amount of prostaglandins.

Ibuklin - combination drug

Contraindications: hypersensitivity to components, gastric ulcer, gastric bleeding, age under 12 years, pregnancy and lactation.

Price: 100-140 rubles.

A new drug of the NSAID group, approved for long-term use. Like the previous remedies, it relieves fever, pain and inflammation by reducing the amount of prostaglandins in the body. It is used for various types of inflammatory pain, as well as for neuralgia and migraine.

Movalis relieves pain and inflammation

Contraindications: age under 16, pregnancy, lactation, stomach ulcers, hepatic and renal colic.

Price: 550-750 rubles.

For spasmodic pain

Pain of a spasmodic nature can occur for various reasons: these include migraine, diseases of the gastrointestinal tract, algomenorrhea and some other conditions. With such a pain syndrome, antispasmodics and complex painkillers with antispasmodic action will help.

Inexpensive and effective pills from the group of antispasmodics, effective Russian analogue But shpy. The effect of their intake is achieved by expanding the smooth muscles of blood vessels and internal organs. It is used for gastroduodenitis, ulcers, cholecystitis, hepatic and renal colic, biliary dyskinesia, colitis and proctitis, intestinal colic and flatulence, dysmenorrhea, as well as during strong contractions during childbirth.

Drotaverine belongs to the group of antispasmodics

Price: 40-80 rubles.

Antispasmodic, used for pain during menstruation, migraines, as well as spasms of the digestive tract, intestinal and biliary colic. Approved for long-term use, has virtually no contraindications. This remedy relieves pain by delivering ionized calcium to smooth muscle cells, which expands smooth muscle and stops spasms.

Sparex approved for long-term use

Contraindications: age under 12 years, hypersensitivity.

Price: 300-370 rubles.

A complex analgesic, consisting of NSAIDs, an antispasmodic and a substance that enhances it. The analgesic effect is achieved by inhibiting prostaglandins and reducing the release of calcium into smooth muscle cells. Eliminates spasmodic pain in the shortest possible time, is used for diseases of the gastrointestinal tract, algomenorrhea, and pyelonephritis.

Spasmalgon is a complex drug

Contraindications: renal and hepatic failure, prostate adenoma, glaucoma and tachyarrhythmia, anemia, leukopenia.

Price: 190-255 rubles.

With oncology

Late stages of development malignant neoplasm the pain can become unbearable. Only the strongest painkillers that cannot be purchased without prescriptions from the attending physician can help get rid of it.

Smooth green tablets belonging to the class of NSAIDs. Ketanov is the most powerful analgesic among non-steroidal anti-inflammatory drugs, the effect of which is achieved due to a sharp decrease in the amount of prostaglandin in the body, and is comparable to narcotic painkillers. The drug is used for postoperative, postpartum and toothaches, for arthrosis, oncology and injuries.

Ketanov - a strong analgesic

Contraindications: age under 16, gastric and intestinal ulcers, gastrointestinal bleeding, bronchial asthma, kidney disease, concomitant use with other NSAIDs.

Cost: 80-145 rubles.

Promedol

Centrally acting narcotic analgesic. It disrupts the transmission of pain impulses, and also changes the perception of pain by the brain. It is actively used not only for oncological diseases, but also after surgery, with peptic ulcer and chronic pancreatitis, myocardial and lung infarction, prostatitis, renal and hepatic colic, neuritis, burns and injuries.

Features of the drug Promedol

Contraindications: age under 2 years, arrhythmia, hyperthyroidism, hypersensitivity to components, alcoholism, convulsions, asthma.

Price: 180-220 rubles.

An opioid analgesic type. A drug with a powerful and fast action, relieving pain in a matter of minutes. The analgesic effect of Tramal is associated with blocking the conduction of pain impulses and with a distortion of the emotional perception of pain. It is used for injuries, after operations and other painful medical manipulations, for pain during the course of myocardial infarction and for oncology.

Tramal is an opioid pain reliever.

Contraindications: age under 16, pregnancy, breastfeeding, renal failure, epilepsy.

Cost: 350-420 rubles.

pain pills during pregnancy

During pregnancy and lactation, it is necessary to carefully choose an analgesic so that the negative effect of the drug does not affect the fetus. Painkillers approved for use during pregnancy and breastfeeding- a little because of the large list of side effects.

There are 2 safe active ingredients a, which can be used to relieve pain during this period:

1. Paracetamol and modern drugs created on its basis. The use of three tablets per day is allowed, the maximum duration of use is 3 days.
2. Drotaverine and No-shpa. You can take no more than 1 tablet per day, and no longer than 3 days in a row.

No-shpu can be taken during pregnancy

Pain pills for children

The children's body is very sensitive to the side effects of drugs, so you should be especially careful with the choice of analgesics for children. Absolutely harmless painkillers do not exist, but there are good and effective analgesics that can be taken at a young age.

List of painkillers approved for children:

1. Paracetamol and its derivatives. Preferably in the form of soluble effervescent tablets.
2. Ibuprofen-based drugs: Nurofen, Ibufen, MIG and others. Only if the child does not chronic diseases GIT.
3. Antispasmodics and combined preparations based on ibuprofen and drotaverine. No more pills a day.
4. Nimesulide-based preparations such as Nimesil, Nimulide and Nimegesic if the child is over twelve years of age.

Painkillers help to fight the syndrome, but are not able to eliminate the root cause. To get rid of pain forever, you need to understand why it occurs and undergo the necessary treatment. Painkillers are good helpers in the treatment of pain, but you cannot rely on them alone.

Analgesics are medicines that can reduce or eliminate pain. There are narcotic and non-narcotic analgesics. Narcotic painkillers are prescribed extremely rarely for certain indications. But we often resort to the use of non-narcotic analgesics if we are worried about pain.

Features of narcotic analgesics

Narcotic painkillers depress the structures of the central nervous system perceiving pain. This group of drugs is represented by opioid receptor agonists: morphine, promedol, codeine, fentanyl, and others.

This group of drugs has a strong analgesic effect. However, narcotic analgesics affect not only the pain center, but also other parts of the central nervous system. So, these drugs depress the respiratory, cough, vasomotor, thermoregulatory centers. In addition, human behavior is disturbed due to a decrease in self-control. To narcotic analgesics, dependence is formed and, as a result, drug addiction.

Important! Given the wide range of side effects, as well as the risk of developing drug dependence, narcotic analgesics can only be used when prescribed by a doctor.

Basically, the use of these drugs is resorted to in acute, life threatening human pain, as well as pain syndrome against the background of inoperable malignant neoplasms.

Features of non-narcotic analgesics

Non-narcotic pain medications reduce the severity of pain and do not affect other structures of the nervous system. The mechanism of their action is based on a decrease in excitability subcortical center pain, an increase in the threshold of its pain sensitivity, inhibition of the synthesis of prostaglandins - inflammatory mediators. Due to this multicomponent action, non-narcotic analgesics have not only analgesic, but also anti-inflammatory, antipyretic effects.

Non-narcotic painkillers have a less pronounced analgesic effect compared to narcotic ones. However, their action is sufficient to relieve muscle pain, which we often encounter. The main advantage of non-narcotic painkillers is the absence of drug dependence on them. It is due to these properties that non-narcotic analgesics are widely used in medicine.

The use of non-narcotic analgesics may be accompanied by the development of side effects:

• Ulcerogenic action (ulceration of the mucous membrane of the stomach, duodenum);
• Nephro- and hepatotoxicity.

The main contraindications to the use of drugs from this drug group are peptic ulcer, blood clotting disorders, hepatic and, pregnancy, lactation.

note : in the annotation for many painkillers, manufacturers indicate that the combined use with other analgesics is contraindicated. This is fraught with the occurrence of undesirable clinical effects.

Popular painkillers

The group of non-narcotic analgesics is represented by a wide variety of synthetic drugs. There are the following non-narcotic analgesics depending on their origin:

1. Derivatives of salicylic acid:;
2. Aniline derivatives:, phenacetin;
3. Derivatives of alkanoic acids: diclofenac sodium;
4. Pyrazolone derivatives: butadione, analgin;
5. Anthranilic acid derivatives: mefenamic acid;
6. Others: piroxicam, dimexide.

In addition, many pharmaceuticals now offer combined medications, which include several drugs at once.

Analgin

This drug is known to everyone, it was synthesized in 1920. And although metamizole sodium (analgin) belongs to the group of NSAIDs, its anti-inflammatory and antipyretic effects are slightly pronounced. But analgin has a pronounced analgesic effect.

Analgin is rapidly absorbed from the gastrointestinal tract, so the analgesic effect occurs quickly, although it does not last very long. Analgin is used for muscle, menstrual pain,.

Important!A dangerous side effect of Analgin is the development of agranulocytosis. it pathological condition, which is characterized by a critical decrease in the level of leukocytes due to granulocytes and monocytes, as a result, the body's susceptibility to all kinds of infections increases. Because of this, Analgin was withdrawn from circulation in many countries. The risk of agranulocytosis when using Analgin is estimated at 0.2-2 cases per million.

Aspirin

Acetylsalicylic acid () is used not only as an analgesic, anti-inflammatory agent. The drug inhibits platelet aggregation, due to which it is used for the prevention of c. However, it is necessary to take into account the fact that in case of violation of blood coagulation (in particular with), bleeding may occur.

Aspirin is not recommended for use in children, especially if a viral infection is suspected. When using aspirin in this case, there is a risk of developing Reye's syndrome. The disease is characterized by rapidly progressive encephalopathy and fatty degeneration of the liver. Mortality in children with Reye's syndrome is approximately 20-30%.

It is also important to consider that with prolonged, uncontrolled use of aspirin, ulceration of the mucous membrane of the stomach and intestines occurs, as well as gastric bleeding. To reduce the ulcerogenic effect, aspirin should be taken after meals.

Ketanov

Ketanov (ketorolac) is a non-narcotic analgesic from the group of acetic acid derivatives. Ketanov is available in the form of tablets, as well as a solution for intramuscular injections. After an intramuscular injection of Ketanov's solution and after taking the tablet, the analgesic effect is noted after half an hour and an hour, respectively. And the maximum effect is achieved after one to two hours.

Ketanov has a pronounced analgesic effect, exceeding the effect of other non-narcotic painkillers. Therefore, it is not surprising that many people with severe toothache, headache, manage to get rid of discomfort only with the help of Ketanov.

In addition to side effects traditional for non-narcotic analgesics, when using Ketanov, side effects from the central nervous system (drowsiness,) may occur. Therefore, when using Ketanov, it is recommended to avoid driving a car.

Dolaren

This is a combination drug that also contains diclofenac sodium. Both of these medicinal substances enhance the action of each other. After using Dolaren tablets, the maximum concentration of active substances is reached after an hour and a half. Many people note a pronounced analgesic effect of Dolaren in comparison with other non-narcotic painkillers.

Dolaren is used for all kinds of diseases of the musculoskeletal system, as well as pain syndrome of any origin. The use of Dolaren will have to be abandoned if there is a hypersensitivity reaction to any NSAIDs, in the period after the operation, hepatic and ulcerative defects of the gastrointestinal tract, gastric bleeding. In addition, the drug is used with caution if a person has chronic and.

Nimesil

The active substance of the drug is nimesulide - it is an NSAID from the class of sulfonamides. Nimesil is available in the form of powder bags. The contents of the sachet must be dissolved in a glass with one hundred milliliters of water.