These drugs selectively reduce, suppress pain sensitivity without significantly affecting other types of sensitivity and without disturbing consciousness (analgesia - loss of pain sensitivity; an - denial, 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 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 us analyze the I-th group of drugs, 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. In 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 referred to in the literature in relation to opiate receptors as 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. By acting 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 non-specific thalamic nuclei, 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 the various other pharmacological effects of 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 the repeated administration of morphine, especially if 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 effect 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 of ​​the 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 of the 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. For 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) - the danger of respiratory depression;

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

3) with a variety of types of respiratory failure (emphysema, bronchial asthma, kyphoscoliosis, obesity);

4) with severe head injuries (increased intracranial pressure; in this case, morphine further increases intracranial pressure and 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. At the same time, it has significantly fewer 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 form of anesthesia itself 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 MORPHINE AND MORPHINE-LIKE DRUGS

Acute poisoning with 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 appears 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. The withdrawal syndrome consists of a number of characteristic signs: 6-10-12 hours after the last injection of morphine, the morphine addict develops rhinorrhea, lacrimation, terrible yawning, chills, goose bumps, hyperventilation, hyperthermia, mydriasis, muscle pain, vomiting, diarrhea, tachycardia, weakness, sweating, sleep disorders, 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, repeated administration of morphine causes very pleasant sensations for the morphine addict in the abdominal cavity, sensations of unusual warmth in the epigastric region and lower abdomen, reminiscent of those during 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 the main reason for limiting 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 of 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. The analgesic activity of non-narcotic analgesics is manifested in certain types of pain: mainly in neuralgic, muscle, joint pain, as well as in headache and toothache.

With severe pain associated with injuries, abdominal surgery, malignant tumors, 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 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 an effective drug for the following types of pain: 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 listed 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, which enter the body 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 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, for fever of infectious and inflammatory origin. The appointment of salicylates in order to reduce body temperature is advisable only at a very high temperature, which adversely affects the patient's condition (39 and 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 connective tissue diseases. 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) A frequent complication when taking salicylates 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 walls. 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 pulmonary vascular diseases. 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 to 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), is part of some soaps, fragrances and drinks (especially birch sap).

Of 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 the elevated body temperature. Analgin is prescribed as an antipyretic only in case of febrile fever, when the drug is the first aid. it is good to remember that you can not inject 1 ml or more, as there may be a lytic temperature drop, which will lead to a temperature collapse.The child is administered 0.3-0.4 ml.As a rule, in this case, dimed is added to the analgin solution

roll. Treatment with analgin is associated with the risk of complications (primarily from the blood side) 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 it 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. 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) acetic acid derivatives: 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 of 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 most good in the 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, ringing in the ears, 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 of adverse reactions is lower. 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. It penetrates well into tissues and 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 action, 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 for RA, chronic rheumatic diseases, and 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.

Medical terms: oncological diseases, neuroleptanalgesia, gout, sciatica, myositis, rheumatism, angina pectoris, myocardial infarction, hepatic and renal colic, keratitis, iritis, cataract, rheumatoid arthritis, osteoarthritis, thrombophlebitis.

Pain sensations occur with destructive harmful stimuli and are danger signals, and in the case of traumatic shock, they can be the cause of death. Eliminating or reducing the severity of pain helps to improve the physical and mental condition of the patient, improve the quality of his life.

There is no pain center in the human body, but there is a system that perceives, conducts pain impulses and forms a reaction to pain - nociceptive (from lat. Therefore- damaging), that is, painful.

Pain sensations are perceived by special receptors - nociceptors. There are endogenous substances that are formed during tissue damage and irritate nociceptors. These include bradykinin, histamine, serotonin, prostaglandins, and substance P (a polypeptide consisting of 11 amino acids).

Types of pain

Superficial epicritical pain, short-term and acute (occurs in case of irritation of nociceptors of the skin, mucous membranes).

Deep pain, has a different duration and ability to spread to other areas (occurs in case of irritation of nociceptors located in muscles, joints, hams).

Visceral pain occurs during irritation of the pain receptors of the internal organs - the peritoneum, pleura, vascular endothelium, meninges.

The antinociceptive system disrupts the perception of pain, the conduction of a pain impulse and the formation of reactions. The composition of this system includes endorphins, which are produced in the pituitary gland, hypothalamus and enter the bloodstream. their excretion increases under stress, during pregnancy, during childbirth, under the influence of dianitrogen oxide, halothane, ethanol, and depends on the state of the higher nervous system (positive emotions).

In case of insufficiency of the nociceptive system (with excessive pronounced and prolonged damaging effect), pain is suppressed with the help of analgesics.

Analgesics (from the Greek. Algos- pain hap- denial) - these are drugs that, with a resorptive action, selectively suppress pain sensitivity. Other forms of sensitivity, as well as consciousness, are preserved.

Classification of analgesics

1. Narcotic analgesics (opioids): opium alkaloids- morphine, codeine, omnopon

Synthetic morphine substitutes: ethylmorphine hydrochloride, promedol, fentanyl, sufentanil, methadone, dipidolor (pyritra-med), estocin, pentazocine, tramadol (tramal), butorphanol (moradol), buprenorphine, tilidine (valorone)

2. Non-narcotic analgesics:

Salicylates- acetylsalicylic acid, acelysin (aspirin), sodium salicylate

Derivatives of pyrazolone and indolic acid: indomethacin (methinodol), butadione, analgin (metamizole-sodium) para-aminophenol derivatives: paracetamol (panadol, lecadol) derivatives of alkanoic acids: ibuprofen, diclofenac sodium (Voltaren, Ortofen), naproxen (Naproxia) - mefenamic acid, sodium mefenaminate, piroxicam, meloxicam (Movalis) Combined drugs: Reopirin, sedalgin, tempalgin, baralgin, citramon, Citropack, tsnklopak, asconar, para vit

Narcotic analgesics

Narcotic analgesics- these are drugs that, with a resorptive action, selectively suppress pain sensitivity and cause euphoria, addiction, and mental and physical dependence (drug addiction).

The pharmacological effects of narcotic analgesics and their antagonists are due to interaction with opioid receptors that are present in the central nervous system and peripheral tissues, as a result of which the process of interneuronal transmission of pain impulses is inhibited.

According to the strength of the analgesic effect, narcotic analgesics can be arranged in the following order: fentanyl, sufentanil, buprenorphine, methadone, morphine, omnopon, promedol, pentazocine, codeine, tramadol.

Pharmacological effects:

- Central: analgesia; respiratory depression (the degree depends on the dose of oshoidiv); inhibition of the cough reflex (this effect is used for coughing, which is accompanied by pain or bleeding - with injuries, rib fractures, abscesses, etc.); sedative effect; hypnotic effect; euphoria - the disappearance of unpleasant emotions, a feeling of fear and tension; nausea and vomiting as a result of activation of dopamine receptors in the trigger zone (occur in 20-40% of patients in response to the first injection of opioids); increased spinal reflexes (knee, etc.); miosis (narrowing of the pupils) - due to an increase in the tone of the nucleus of the oculomotor center;

- Peripheral: obstipation effect associated with the occurrence of spastic contractions of sphincters, restriction of peristalsis; bradycardia and arterial hypotension due to increased tone of the nucleus of the vagus nerve increased tone of the smooth muscles of the bladder and urethral sphincter (renal colic and urinary retention, which are undesirable in the postoperative period); hypothermia (this is how the patient should be warmed and often change the position of the body in bed).

Morphine hydrochloride- the main alkaloid of opium, which was isolated in 1806 by V.A. Serturner and named after the Greek god of sleep, Morpheus (opium is the dried juice from the heads of the sleeping poppy, contains more 20 alkaloids). Morphine is the main drug of the group of narcotic analgesics. It is characterized by a strong analgesic effect, pronounced euphoria, and with repeated injections, drug dependence (morphinism) quickly occurs. Characteristic is the depression of the respiratory center. Taking the drug in low doses causes a slowdown and increase in the depth of respiratory movements, in high doses it contributes to a further slowdown and decrease in the depth of breathing. Use in toxic doses leads to respiratory arrest.

Morphine is rapidly absorbed both when administered orally and subcutaneously. The action occurs 10-15 minutes after subcutaneous administration and 20-30 minutes after ingestion and lasts 3-5 hours. It penetrates well through GBB and the placenta. Metabolism occurs in the liver and is excreted in the urine.

Indications for use: as an anesthetic for myocardial infarction, in the pre- and postoperative period, for injuries, oncological diseases. Assign subcutaneously, as well as inside in powders or drops. Children under 2 years of age are not prescribed.

Codeine is used as an antitussive or dry cough because it suppresses the cough center to a lesser extent.

Ethylmorphine hydrochloride(dionin) - surpasses codeine in the strength of analgesic and antitussive action. When introduced into the conjunctival sac, it improves blood and lymph circulation, normalizes metabolic processes, helps to eliminate pain and resolve exudates and infiltrates in case of eye tissue disease.

It is used for cough and pain syndrome caused by bronchitis, bronchopneumonia, pleurisy, as well as keratitis, iritis, iridocyclitis, traumatic cataract.

Omnopon contains a mixture of opium alkaloids, including 48-50% morphine and 32-35% other alkaloids. The drug is inferior in analgesic effect to morphine and gives an antispasmodic effect (contains papaverine).

It is used in such cases as morphine, but omnopon is more effective for spastic pain. Enter subcutaneously.

Promedol- Synthetic analgesic. In terms of analgesic effect, it is 2-4 times inferior to morphine. The duration of action is 3-4 hours. Less likely than morphine, it causes nausea and vomiting, and to a lesser extent it depresses the respiratory center. Reduces the tone of smooth muscles of the urinary tract and bronchi, increases the tone of the intestines and biliary tract. Enhances rhythmic contractions of the myometrium.

Indications for use: as an anesthetic for injuries, in the pre- and postoperative period. Assign to patients with gastric ulcer and duodenal ulcer, angina pectoris, myocardial infarction, intestinal, hepatic and renal colic and other spastic conditions. In obstetrics, it is used to anesthetize childbirth. Assign subcutaneously, intramuscularly and inside.

Fentanyl- a synthetic drug, superior in analgesic effect to morphine by 100-400 times. After intravenous administration, the maximum effect is observed after 1-3 minutes, which lasts 15-30 minutes. Fentanyl causes pronounced (up to respiratory arrest), but short-term depression of the respiratory center. Increases the tone of skeletal muscles. Bradycardia often occurs.

Indications for use: for neuroleptanalgesia in combination with neuroleptics (thalamonal or inovar). The drug can be used to relieve acute pain in myocardial infarction, angina pectoris, renal and hepatic colic. Recently, a transdermal fentanyl system has been used for chronic pain syndrome (valid for 72 hours).

Pentazocine hydrochloride- leads to less mental dependence, increases blood pressure.

Butorphanol(moradol) is similar in pharmacological properties to pentazocine. It is prescribed for severe pain, in the postoperative period, for cancer patients, in case of renal colic, injuries. Enter intramuscularly at 2-4 mg of a 0.2% solution or intravenously at 1-2 mg of a 0.2% solution.

Tramadol- a strong analgesic of the central action. There are two mechanisms of action associated with opioid receptors, due to which the sensation of pain is weakened, and also inhibits the reuptake of noradrenaline, as a result of which the transmission of pain impulses in the spinal cord is inhibited. Tramadol does not suppress respiration and does not cause dysfunction of the cardiovascular system. The action comes on quickly and lasts for several hours.

Indications for use: severe pain of various origins (due to trauma), pain after diagnostic and therapeutic procedures.

Side effects when using narcotic analgesics and measures to eliminate them:

Respiratory depression, as well as depression of the respiratory center in the fetus (in the umbilical vein - naloxone)

Nausea, vomiting (antiemetics - metoclopramide)

Increased smooth muscle tone (administered with atropine)

Hyperemia and itching of the skin (antihistamines)

Bradycardia

Constipation (laxative - senna leaves)

Tolerance;

Mental and physical dependence.

In acute poisoning with narcotic analgesics the function of the central nervous system is suppressed, characterized by loss of consciousness, slowing down of breathing until it stops, a decrease in blood pressure and body temperature. The skin is pale and cold, the mucous membranes are cyanotic. Characteristic features are pathological respiration of the Cheyne-Stokes type, preservation of the tendon reflex and pronounced miosis.

Treatment of patients with acute poisoning with narcotic analgesics:

Gastric lavage, regardless of the route of administration, with a 0.05-0.1% solution of potassium permanganate;

Reception of 20-30 g of activated carbon

Salt wash;

Intravenous and intramuscular administration of the naloxone antagonist (narcan). The drug acts quickly (1 min), but not for long (2-4 hours). For long-term action, nalmefene should be administered intravenously (10 hours are effective);

Artificial respiration may be necessary;

Warm up the patient.

If death does not occur in the first 6-12 hours, then the prognosis is positive, since most of the drug is inactivated.

With prolonged use of narcotic analgesics, drug dependence of the opioid type develops, which is characterized by tolerance, mental and physical dependence, as well as withdrawal symptoms. Tolerance appears after 2-3 weeks (sometimes earlier) with the introduction of the drug in therapeutic doses.

After stopping the use of opioid analgesics, tolerance to euphoria and respiratory depression decreases after a few days. Mental dependence - euphoria that occurs when using narcotic analgesics and is the root cause of uncontrolled drug use, especially quickly occurs in adolescents. Physical dependence is associated with withdrawal syndrome (withdrawal syndrome): lacrimation, hyperthermia, sudden changes in blood pressure, muscle and joint pain, nausea, diarrhea, insomnia, hallucinations.

The constant use of opioids leads to chronic poisoning, in which mental and physical performance decreases, exhaustion, thirst, constipation occur, hair falls out, etc.

Treatment of drug dependence on opioids is complex. These are methods of detoxification, the introduction of the opioid antagonist - naltrexone, symptomatic drugs and the implementation of measures to prevent the addict from contacting the familiar environment. However, a radical cure is achieved in a small percentage of cases. Most patients relapse, so preventive measures are important.

Pharmacosecurity:

- It must be remembered that narcotic analgesics are poisonous drugs of list A, they should be prescribed on special forms, they are subject to quantitative accounting. Extract and storage are regulated;

- For abuse, misuse - criminal liability;

- Morphine is not compatible in one syringe with chlorpromazine;

- Promedol is not compatible with antihistamines, tubocurarine, trazikor;

- The injectable form of tramadol is not compatible with solutions of diazepam, flunitrozenam, nitroglycerin;

- Do not inject pentazocine with barbiturates in the same syringe;

- Opium preparations inhibit intestinal motility and may delay the absorption of other drugs that are administered orally;

- Codeine in the composition of complex preparations practically does not cause addiction and addiction.

Narcotic analgesics

Non-narcotic analgesics

Non-narcotic analgesics (analgesics-antipyretics) are drugs that eliminate pain during inflammatory processes and give antipyretic and anti-inflammatory effects.

Inflammation is a universal reaction of the body to the action of various (damaging) factors (causative agents of infections, allergic, physical and chemical factors).

The filling process involves various cellular elements (labrocytes, endothelial cells, platelets, monocytes, macrophages), which secrete biologically active substances: prostaglandins, thromboxane AZ, prostacyclin - inflammatory mediators. Enzymes of cyclookeigenase (COX) also contribute to the production of inflammatory mediators.

Non-narcotic analgesics block COX and inhibit the formation of prostaglandins, causing anti-inflammatory, antipyretic and analgesic effects.

The anti-inflammatory effect is that the exudative and proliferative phases of inflammation are limited. The effect is achieved in a few days.

Analgesic effect seen after a few hours. Drugs affect mainly pain in inflammatory processes.

Antipyretic effect manifests itself with hyperpyrexia after a few hours. At the same time, heat transfer increases due to the expansion of peripheral vessels and sweating increases. It is not advisable to reduce body temperature to 38 ° C, since subfebrile temperature is a protective reaction of the body (phagocyte activity and interferon production increase, etc.).

Salicylates

Acetylsalicylic acid(aspirin) - the first representative of non-narcotic analgesics. The drug has been used since 1889. It is available in tablets, it is part of such combined preparations as citramon, sedalgin, cofitsil, alka-seltzer, jaspirin, tomapirin, etc.

Indications for use: as an analgesic and antipyretic (for fever, migraine, neuralgia) and as an anti-inflammatory agent (for rheumatism, rheumatoid arthritis); the drug has an antiaggregatory effect, it is prescribed for the prevention of thrombotic complications in patients with myocardial infarction, cerebrovascular accidents and other cardiovascular diseases.

Side effect irritation of the gastric mucosa, stomach pain, heartburn, ulcerogenic effect (formation of stomach ulcers), Reye's syndrome.

Soluble form of aspirin - acelysin.

It is administered intramuscularly and intravenously as an anesthetic in the postoperative period, with rheumatic pain, oncological diseases.

Sodium salicylate as an analgesic and antipyretic, it is prescribed orally after meals for patients with acute rheumatism and rheumatoid endocarditis, sometimes administered intravenously.

Derivatives of pyrazolone and indoloctic acid

Analgin(metamizol-sodium) - has a pronounced analgesic, anti-inflammatory and antipyretic effect.

Indications for use: with pain of various origins (headache, toothache, trauma pain, neuralgia, radiculitis, myositis, fever, rheumatism). Assign inside after a meal for adults, and also administered intramuscularly and intravenously.

Side effect edema, increased blood pressure, toxic effects on hematopoiesis (blood count changes).

Butadion(hair dryer and forehead and zones) - has an analgesic, antipyretic and anti-inflammatory effect. The anti-inflammatory effect of butadione is more pronounced than in salicylates.

Assign for arthritis of various etiologies, acute gout. Applied orally during or after meals. The duration of the course of treatment is from 2 to 5 weeks. With thrombophlebitis of the superficial veins, butadione ointment is used, but due to the large number of side effects in our time, the use of butadione is limited.

Indomethacin(metindol) - has a pronounced analgesic, anti-inflammatory and antipyretic effect. Assign to patients with rheumatoid arthritis, osteoarthritis, gout, thrombophlebitis. Applied inside, and indomethacin ointment is rubbed with acute and chronic polyarthritis, sciatica.

Para-aminophenol derivatives

Paracetamol(panadol, efferalgan, tylenol) - according to the chemical structure, it is a metabolite of phenacetin and gives the same effects, but is less toxic compared to phenacetin. Used as an antipyretic and analgesic. Abroad, paracetamol is produced in various dosage forms: tablets, capsules, mixtures, syrups, effervescent powders, as well as in the composition of such combined preparations as coldrex, solpadein, pa on dol-extra.

Derivatives of alkanoic acids

Diclofenac sodium (ortofen, voltaren) is an active anti-inflammatory agent. It has a pronounced analgesic effect, and also has antipyretic activity. The drug is well absorbed from the digestive tract, almost completely bound to plasma proteins. Excreted in urine and bile as metabolites. The toxicity of diclofenac sodium is low, the drug is characterized by a significant breadth of therapeutic action.

Indications for use: rheumatism, rheumatoid arthritis, arthrosis, spondylarthrosis and other inflammatory and degenerative diseases of the joints, postoperative and post-traumatic edema, neuralgia, neuritis, pain syndrome of various origins as an adjuvant in the treatment of people with various acute infectious and inflammatory diseases.

ibuprofen(Brufen) - has a pronounced anti-inflammatory, analgesic and antipyretic effect due to the blockade of prostaglandin synthesis. In patients with arthritis, it reduces the severity of pain and swelling, increases the range of motion in them.

Indications for use: rheumatoid arthritis, osteoarthritis, gout, inflammatory diseases of the musculoskeletal system, pain syndrome.

Naproxen(naproxia) - a drug that is inferior in anti-inflammatory effect to diclofenac sodium, but exceeds its analgesic effect. It has a longer effect, so naproxen is prescribed 2 times a day.

Preparations of a chemical structure

Ketorolac(ketanov) has a pronounced analgesic activity, significantly superior to the activity of other non-narcotic analgesics. Less pronounced are antipyretic and anti-inflammatory effects. The drug blocks COX-1 and COX-2 (cyclooxygenase) and thus prevents the formation of prostaglandins. Assign adults and children over 16 years of age inside with injuries, toothache, myalgia, neuralgia, sciatica, dislocations. It is administered intramuscularly for pain in the postoperative and post-traumatic periods, injuries, fractures, dislocations.

Side effects: nausea, vomiting, stomach pain, liver dysfunction, headache, drowsiness, insomnia, increased blood pressure, palpitations, allergic reactions.

Contraindications: period of pregnancy and lactation, children under 16 years of age. Carefully appoint patients with bronchial asthma, impaired liver function, heart failure.

Mefenamic acid- inhibits the formation and eliminates inflammation from tissue depots of mediators (serotonin, histamine), inhibits the biosynthesis of prostaglandins, etc. The drug enhances cell resistance to damaging effects, well eliminates acute and chronic toothache and pain in muscles and joints; exhibits an antipyretic effect. Unlike other anti-inflammatory drugs, it almost does not show an ulcerogenic effect.

Sodium mefenaminate- similar in action to mefenamic acid. When applied topically, it accelerates the healing of wounds and ulcers.

Indications for use: ulcerative stomatitis, periodontal disease, toothache, sciatica.

Piroxicam- anti-inflammatory agent with analgesic and antipyretic effects. Inhibits the development of all symptoms of inflammation. It is well absorbed from the digestive tract, binds to blood plasma proteins, and acts for a long time. It is excreted mainly by the kidneys.

Indications for use: osteoarthritis, spondylarthrosis, rheumatoid arthritis, sciatica, gout.

Meloxicam(Movalis) - selectively blocks COX-2 - an enzyme that is formed in the focus of inflammation, as well as COX-1. The drug has a pronounced anti-inflammatory, analgesic and antipyretic effect, and also eliminates local and systemic symptoms of inflammation, regardless of location.

Indications for use: for symptomatic therapy of patients with rheumatoid arthritis, osteoarthritis, arthrosis with severe pain syndrome.

In recent years, drugs with a greater selective effect than meloxicam have been created. Thus, the drug celecoxib (Celebrex) is hundreds of times more active in blocking COX-2 than COX-1. A similar drug - rofecoxib (Viox) - selectively blocks COX-2.

Side effects of non-narcotic analgesics

Irritation of the mucous membrane of the digestive tract, ulcerogenic effect (especially when using acetylsalicylic acid, indomethacin, butadione)

Edema, fluid and electrolyte retention. Occur 4-5 days after taking the drug (especially butadione and indomethacin)

Reye's syndrome (hepatogenic encephalopia) is manifested by vomiting, loss of consciousness, coma. May occur in children and adolescents due to the use of acetylsalicylic acid for influenza and acute respiratory infections;

Teratogenic effect (acetylsalicylic acid and indomethacin should not be prescribed in the first trimester of pregnancy)

Leukopenia, agranulocytosis (especially in pyrazolone derivatives)

Retinopathy and keratopathy (due to deposition of indomethacin in the retina)

allergic reactions;

Hepato- and nephrotoxicity in paracetamol (with prolonged use, especially at high doses);

hallucinations (indomethacin). With caution appoint patients with mental disorders, with epilepsy and parkinsonism.

Pharmacosecurity:

- It is necessary to explain to the patient that the uncontrolled use of drugs that are potent substances is harmful to the body;

- To prevent the damaging effect of drugs on the mucous membranes, the patient should be taught to take drugs correctly (with food, milk or a full glass of water) and recognize the signs of gastric ulcer (not digesting food in the stomach, vomiting "coffee grounds", tarry stools);

- To prevent the development of agranulocytosis, it is necessary to monitor the blood test, warn the patient about the need to inform the doctor in case of symptoms of agranulocytosis (feeling cold, fever, sore throat, malaise)

- To prevent nephrotoxicity (hematuria, oliguria, crystalluria), it is necessary to control the amount of urine output, warn the patient about the importance of informing the doctor if any symptoms appear

- Remind the patient that in case of drowsiness after taking indomethacin, one should not drive a car and work with dangerous equipment;

- Non-narcotic analgesics are not compatible with sulfa drugs, antidepressants, anticoagulants;

- Salicylates should not be prescribed together with other non-paranotic analgesics (increased ulcerogenic action) and anticoagulants (increased risk of bleeding).

Painkillers are one of the essentials, because pain can occur suddenly and signal a variety of disorders in our body.

Headache, toothache, back pain, symptomatic pain in various diseases - all this requires an immediate response, which means that a suitable effective remedy should be at hand.

The main thing in the article

Many analgesics are sold without a prescription, and when buying them, it is important to take into account the principle of their action, the most appropriate dosage form, indications, contraindications, and other factors.

Painkillers are drugs that relieve pain syndromes of different localization and belong to the group of opioids, non-opioids or combined drugs.

Ideally, a healthy person should not experience pain, so its occurrence cannot be ignored, but it is also not worth drowning it out uncontrollably with analgesics.

It is important to remember one thing: an anesthetic drug, no matter how modern and safe it may be, is not able to get rid of the cause of the pain syndrome, but only temporarily eliminates discomfort.

If the pain appeared suddenly, it is permanent and does not allow you to freely engage in daily activities, you should seek medical help and take analgesics only as directed by a doctor and after a detailed examination aimed at establishing a diagnosis.

Pain relievers, depending on their composition and dosage form, can have both a local analgesic effect and a systemic effect on the central nervous system and brain.

Today, painkillers are represented by many groups, each of which is designed to save a person from a certain type of pain syndrome. How to understand the variety of means for relieving pain? How to choose the safest of them? Let's try to answer these questions.

Classification and types of painkillers

The answer to the question of which remedies will most effectively help relieve pain and which one to take for this or that type of pain can only be given by a doctor, based on the symptoms and.

But today, all analgesics are divided into two large pharmacological groups:

• narcotic;
• non-narcotic.

The mechanism of action of narcotic painkillers is based on the inhibition of the activity of the central nervous system. The active ingredients of these drugs are able to change the nature of pain due to a direct effect on the human brain. As a result, not only the pain syndrome subsides, but also a feeling of euphoria sets in.

However, narcotic analgesics carry a certain danger - they cause drug dependence, so they can only be purchased by prescription, and taken only under the supervision of the attending physician.

Such drugs are used for myocardial infarction, serious burns and fractures, cancer and other serious conditions. This group includes drugs based on morphine, codeine, fentanyl, as well as such modern drugs as Nurofen Plus and Sedalgin Neo.

Non-narcotic painkillers do not affect the central nervous system, and therefore they do not have the disadvantages inherent in narcotic drugs. They do not form a dependence in the patient, do not cause drowsiness and other side effects from the use.

However, in addition to analgesic, they also have anti-inflammatory properties due to the suppression of the production of inhibitors of the inflammatory response - prostaglandins. are very effective, and therefore are included in a comprehensive treatment regimen for many diseases.

Depending on the principle of action and composition, all non-narcotic analgesics are divided into several subgroups:

• simple or traditional - pyrozolones and preparations based on their derivatives (Spazgan, Spazmolgon, Analgin, Tempalgin, Baralgin, etc.);
• combined - include several active components at once, which have an analgesic effect; as a rule, this is a combination of paracetamol with some synthetic substance, which provides not only analgesic, but also antipyretic and antispasmodic effects (Pentalgin, Ibuklin, Vix Active Symptomax, Caffetin, Trigan, etc.);
• drugs for migraine attacks - as a rule, migraine cannot be stopped with conventional analgesics, therefore, in this case, drugs are used that additionally have antispasmodic and vasodilating properties (Sumatriptan, Frovatriptan, Relpax, etc.);
• non-steroidal anti-inflammatory drugs (NSAIDs) - effective in relieving pain, fever and inflammation; used for headache, toothache, diseases of the joints and spine, osteochondrosis, arthrosis, rheumatism and other pathologies accompanied by inflammation and pain (Nurofen, Ibuprofen, Nalgezin, Ketorol, Ketanov, Dolomin, Naproxen, etc.);
• COX-2 inhibitors (coxibs) - belong to the group of NSAIDs, but are separated into a separate subgroup of drugs that protect the gastric mucosa and do not adversely affect the gastrointestinal tract; used to relieve pain in gastritis and ulcers, as well as joint diseases (Parecoxib, Etoricoxib, Celecoxib, Omeprazole);
• antispasmodics - painkillers that relax smooth muscles and dilate blood vessels, due to which analgesia is provided (Drotaverine hydrochloride, No-shpa, Nomigren).

As you can see, the list of analgesic drugs is quite extensive, and it can be difficult for a person without special education to understand it.

Most Common Analgesics: Side Effects and Dangerous Interactions

For many years, four drugs have been leaders among all painkillers - analgin, paracetamol, ibuprofen and acetylsalicylic acid, better known as aspirin.

Despite the fact that they all differ in antipyretic and anti-inflammatory effect, they relieve pain equally well.

The fact that all of the above medicines are dispensed to anyone without a doctor's prescription creates a false illusion of their safety.

And analgin, and paracetamol, and ibuprofen, and aspirin have an impressive list of contraindications and side effects, so they should be taken with great care.

They can also interact with drugs of other pharmacological groups, enhancing undesirable effects or creating dangerous drug combinations. Even tea and sour juice can change the properties of these remedies.

Table 1. Side effects of the most common analgesics

Table 2. Interaction of analgesics with drugs of other groups

Risks of co-administration of drugs, alcohol and other beverages

Analgesics in the form of ointments for external use

A modern person every day performs a wide variety of actions, most of which can cause pain in different parts of the body. Anesthetic ointments for external use are designed to reduce it.

There are ointments for pain in muscles and joints, even ointments with an anesthetic to reduce sensitivity when tattooing or epilating. Some of them are allowed to be used by women during the period of bearing a child. Such a tool can be easily purchased at any pharmacy in any city.

Operating principle

A feature of the use of ointments for external use is that they are applied directly to the sore spot.

Pain-relieving ointments for external use contain specific components, conditionally divided into 2 categories:

• blocking the transmission of impulses from the receptor to the brain;
• blocking pain in the focus of its occurrence through the suppression of the synthesis of inhibitors of pain and inflammation - prostaglandins.

The composition of anesthetic ointments includes special components that penetrate into the deep layers of the epidermis - to the very epicenter of pain. Most often, such funds are used for joint injuries. They cool the injured area, but do not reduce body temperature.

There is only a slight feeling of coolness, which is provided by menthol or mint extract, which are part of the drug. An analgesic, anticoagulant, special oil or specific alcohol additives are also capable of providing cooling.

Each of the anesthetic ointments has its own trade name, but people are often confused, not understanding which ointment is exactly the anesthetic. Therefore, the use of such ointments without consulting a specialist and his appointment is undesirable.

The doctor will inform about the properties of the drug, the method of its application, the layer, the conditions of use for various injuries and pathologies.

In addition, any ointment, like any drug, has a number of contraindications. These include disorders of kidney and liver function, eye diseases, individual intolerance to components, pregnancy and breastfeeding.

Anesthetic ointments are very effective for neuralgia. They are prescribed as part of complex therapy and are able to save the patient from unpleasant symptoms, have a beneficial effect on his general condition.

Effects of using local anesthetics in the form of a gel or ointment:

• acceleration of blood flow in the damaged area;
• normalization of metabolism;
• relieving muscle tension;
• strengthening ligaments, restoring their elasticity;
• warming the affected area;
• reduction of pain and discomfort.

Any anesthetic ointment will speed up recovery. Some ointments are used as a distraction - they contain a component such as capsaicin or red pepper extract, which causes a burning sensation, making a person forget about pain for a while.

You can understand that the drug has begun its action by the appearance of a feeling of warmth in the injured area.

Medicines

The most popular for external use today are:

1. Ketonal Gel - a drug in the form of a gel based on ketoprofen, is prescribed for injuries and sprains, sciatica, rheumatoid arthritis, myalgia and other diseases of the musculoskeletal system; it is recommended to use the course no more than 14 days;
2. Viprosal - an ointment based on viper poison and a composition of essential oils; immediately after application, a specific tingling sensation is felt, then the pain recedes;
3. Finalgon is a popular remedy based on the synthetic component of nonivamide, which has the same properties as capsaicin, and nicotinic acid ester; warms the sore spot, relieves pain, stimulates blood circulation; often used for neuralgia; it is recommended to use 3 times a day for a course of no more than 10 days;
4. Apizartron - an ointment for bruises based on bee venom, methyl salicylate, allyl isothiocyanate; locally affects the pain, completely relieves it; normalizes cellular metabolism, accelerates blood flow, helps saturate the bruised area with oxygen, has a warming effect;
5. Myoton - is considered one of the most effective ointments for relieving pain; relieves muscle tension, stimulates blood flow, warms, effectively relieves pain;
6. Voltaren Emulgel is an ointment based on diclofenac, which has many contraindications and side effects; it is recommended to use as prescribed by a doctor and a course of no more than 2 weeks;
7. Fastum Gel is another remedy based on ketoprofen; used as an anesthetic ointment for joints; recommended course use lasting no more than 2 weeks;
8. Deep Relief Gel - a drug based on ibuprofen and levomenthol; effectively reduces pain and swelling, relieves inflammation; a course of treatment of at least 10 days is recommended;
9. Dolgit - ointment, the active substance of which is ibuprofen; well relieves pain and swelling, allows you to increase joint mobility, helps reduce the likelihood of morning stiffness of the joints after sleep; the course of treatment is long - not less than 1 month.
10. Emla is one of the most expensive lidocaine-based pain relievers, most often used to reduce pain during epilation; feature of the application - no need to rub the product - it is enough to apply it in a thin layer.

Lidocaine is also the main active ingredient in the ointment to relieve pain after applying and reducing tattoos.

Herbal ointments

People today give more preference to external preparations based on natural plant components - they cause fewer allergic reactions and are much cheaper than preparations based on synthetic active ingredients.

These are various ointments based on snake and bee venom, based on extracts of medicinal plants (mint, lingonberry, sage, fir, linden, chamomile, rosemary, etc.). The most popular representative of this family of anesthetic ointments is a drug called Collagen Ultra, which any patient can use without fear.

Contraindications

Like any drug, anesthetic ointment for external use has a number of contraindications. Almost every remedy mentioned above is intended for only a small category of patients.

First of all, they are for lactating women, people suffering from skin diseases, which can only be aggravated by contact with a gel or ointment. Do NOT forget about individual intolerance.

Before prescribing this or that ointment, the doctor must make sure that the patient has healthy kidneys, liver, heart, blood vessels, stomach and intestines. A strict contraindication to the use of this or that anesthetic ointment is the presence of diabetes in the patient.

Such drugs are contraindicated in persons younger than 14 and older than 65 years. For people suffering from bronchial asthma, they are prescribed with extreme caution, since many herbal ingredients can provoke an asthma attack. Of course, it is worth remembering that before using this or that external preparation, it is necessary to consult a specialist.

Analgesics in tablet form

Pain that is not treated is a strong stress not only for the physical health of a person, but also for his mental state.

Fortunately, modern medicine has learned how to cope with it - today doctors are armed with dozens of analgesics, among which tablet forms are most often used.

For headache

For the treatment of so-called tension headaches caused by stress, overwork, lack of sleep or viral infections, simple and inexpensive pain pills are used. For migraine attacks, stronger drugs are prescribed - most often from the triptan group.

Among the simple drugs for headaches are:

1. Analgin (Tempalgin, Baralgin) is an inexpensive analgesic drug from the group of non-narcotic analgesics based on metamizole sodium; it has been proven that the drug has the ability in rare cases to cause a condition such as agranulocytosis, and also has allergic properties, so today they are trying to replace it with more modern and safer analogues; contraindicated in blood diseases, pregnancy, impaired functioning of the kidneys and liver;
2. Citramon is a combination drug based on paracetamol, acetylsalicylic acid and caffeine; dilates blood vessels, relieves spasms, has an anti-inflammatory effect; used for pain of unknown origin, contraindicated in violations of blood clotting, liver and kidney function, gout, gastritis and stomach ulcers;
3. Sumatriptan - a drug prescribed for migraine attacks; taken under the supervision of a doctor, as it has a lot of contraindications and side effects from the cardiovascular, nervous, digestive and respiratory systems.

For the relief of headaches are also used - Pentalgin, Solpadein. With pain caused by spasm, No-shpa, Spazgan will help. Spasmalgon, Buscopan, which are also often used as painkillers for menstruation in women.

In inflammatory processes in the body, accompanied by a headache, it is worth taking Aspirin, Ibuprofen. Nurofen, Ibuklin, Ketoprofen, Diclofenac.

For toothache

Toothache brings a lot of physical and mental suffering to a person, so it must be stopped as soon as possible. Painkillers for toothache eliminate an unpleasant symptom, but they cannot replace dental treatment, so it is better not to delay contacting a doctor.

The most commonly used drugs for toothache are:

1. Nise (Nimesil) - a powerful non-steroidal anti-inflammatory drug based on nimesulide; indicated for pulpitis, periodontitis and other inflammatory diseases of the teeth and oral cavity; contraindicated in gastric ulcer and duodenal ulcer, kidney and liver disease, pregnancy and breastfeeding period;
2. Ketorol (Ketorolac, Ketanov) is a strong pain reliever that effectively relieves toothache and other types of pain; advantages - long-term effect (up to 8 hours); toxic, has a lot of contraindications, so self-treatment is highly undesirable for them;
3. Nurofen is a drug from the NSAID group, which effectively relieves not only toothache, but also headache, joint and other types of pain; should be taken in a short course, strictly observing the dosage and informing the doctor about all changes in well-being during the reception.

Also, to relieve toothache, you can use Analgin, Spazgan, Spazmalgon, No-shpu, Pentalgin and other similar drugs.

For joint and muscle pain

Joint pain can occur as a result of trauma, inflammation, degenerative changes. Therefore, it is recommended to select an anesthetic taking into account the nature and cause of an unpleasant symptom.

With arthrosis and arthritis, as a rule, the choice falls on drugs from the group of NSAIDs based on ibuprofen, diclofenac, indomethacin.

In severe cases, with pain in the joints, narcotic analgesics can be prescribed - Tramadol, Tramal, Promedol, etc.

Medicines most commonly prescribed by doctors for joint and muscle pain include:

1. Texamen is a powerful analgesic from the group of non-steroidal anti-inflammatory drugs; quickly relieves inflammation and eliminates the source of pain, like all medicines from this family, it has a lot of contraindications and side effects that cannot be ignored when prescribing;
2. Diclofenac - tablet forms of this inexpensive drug are recommended for muscle and joint pain; relieves inflammation, reduces swelling, improves joint mobility; compared to other drugs, it has not so many contraindications - these include childhood, blood diseases, peptic ulcer, impaired kidney and liver function, pregnancy and lactation.

To relieve pain in the joints and muscles, the attending physician may prescribe a reception (Meloxicam, Piroxicam), which are effective and have a relatively small number of side effects.

In orthopedic and traumatological practice, nimesulide and celecoxib preparations are widely used, as well as powerful tablets with prolonged action (Ketorol, Ketanov), which relieve pain and inflammation. In difficult cases, narcotic analgesics are used.

For back pain

Back pain is a frequent companion of such diseases as osteochondrosis, spondylosis, arthrosis, arthritis, sciatica, sciatica and others. Most often, for back pain, drugs from the group of non-steroidal anti-inflammatory drugs, non-narcotic analgesics are prescribed. For severe pain, painkillers from the narcotic group can be used.

Popular home remedies for back pain relief include:

• Naproxen - NSAID based on naphthylpropionic acid, extremely effective in relieving pain, swelling and fever; indicated for neuralgia, myalgia and other pathologies of the musculoskeletal system; in general, the drug is well tolerated, having much fewer side effects from various organs and systems than other drugs in this group;
• Indomethacin - pills known to many that have analgesic, decongestant, antipyretic and anti-inflammatory effects; indicated for inflammation of the joints and muscles, with diseases of the spine; taken with caution, as it has an extensive list of contraindications and side effects.

With hemorrhoids

Hemorrhoids are varicose veins that form knots around the rectum. With the development of this disease, pain is inevitable, and if at the beginning it is observed only when visiting the toilet, then after some time it becomes a constant companion of a person. Painkillers for hemorrhoids are prescribed only by a proctologist.

The most common pills for this condition are:

• Detralex - a venotonic based on diosmin and flavonoids, relieves pain within an hour after ingestion; increases vein tone, reduces vascular permeability, prevents bleeding; well tolerated, has almost no contraindications (only the period of breastfeeding and rare individual intolerance to the components of the drug);
• Phlebodia is a French-made venotonic that effectively relieves pain and swelling, stimulates blood and lymph circulation, and eliminates congestion; one of the most effective remedies for hemorrhoids, which fights not only with pain, but also with the cause of its occurrence; the action lasts at least 5 hours.

Also, to relieve pain, you can take Ibuklin, Pentalgin, Nise, Asklezan and other drugs prescribed by your doctor.

The most powerful analgesics in tablet form

Among the most powerful painkillers are opioid-based analgesics - Promedol, Tramal, Tramadol, Fentanyl, Morphine, Codeine. Fentanyl is part of a modern analgesic, such as a skin anesthetic patch, which is often prescribed to patients with malignant tumors.

They effectively relieve pain and give a feeling of euphoria, but this advantage does not cover such a disadvantage as the formation of drug dependence. The funds are not prescribed for children (except for cases of intractable pain syndrome in oncological diseases), as well as for pregnant women and nursing mothers.

In any case, narcotic analgesics are not used unless absolutely necessary, and it is impossible to buy them at a pharmacy without a doctor's prescription.

Among non-steroidal anti-inflammatory drugs, Ketonal, Meloxam, Solpadein, Nalgezin, Spazgan, Nalgezin, Sedalgin, Celebrex are most effective.

Before taking any drug to relieve pain, a specialist consultation is necessary - he will be able to determine the cause and prescribe adequate treatment in order to forget about the discomfort as soon as possible.

Analgesics in the form of injections

As mentioned above, pain has different prerequisites - it appears as a result of trauma, spasms, exacerbation of a chronic disease, or other causes. In some cases, the pain can be so severe that it causes pain shock, which, in fact, is a threatening condition.

Then it is painkillers that can save a person's life. What drugs are used for them?

As a rule, injectable analgesics are prescribed to patients in the postoperative period, with serious injuries and burns. Today, there are a lot of analgesics in injections that can reduce human suffering.

It is worth noting that such tools have different names and are designed for different situations. Pain injections are often prescribed for back pain, toothache, menstrual pain, or pain caused by injury or chronic disease.

For toothache

Dentists use drugs for or to relieve toothache that block the transmission of nerve impulses only in a certain area. Most of them are products based on lidocaine, articaine, mepivocaine.

These include:

1. Mepivastezin;
2. Septodont;
3. Ultracain;
4. Septonest;
5. Ubestesin.

With hemorrhoids

If the pain from inflamed hemorrhoids is unbearable, the patient is prescribed a novocaine blockade - an anesthetic injection into the tissues located near the anus. With an anal fissure, injectable drugs are prescribed, such as, for example, Baralgin or Spazmolgon.

"Ketorol": indications and action

"Ketorol" is a drug from the group of NSAIDs based on ketorolac, which effectively relieves pain and reduces body temperature. It blocks the synthesis of inflammation modulators - prostaglandins, as well as the activity of the cyclooxygenase enzyme, due to which an anti-inflammatory effect is achieved. The analgesic effect occurs approximately half an hour after the administration of the drug.

Indications for the use of the drug "Ketorol":

• pain in the back, joints and muscles;
• osteochondrosis of any part of the spine;
• radiculitis;
• neuralgia;
• joint and ligament injuries;
• fractures;
• sprains, sprains and bruises;
• toothache, tooth extraction;
• headache;
• periodic pain in women;
• postoperative period;
• burns;
• malignant tumors.

"Ketonal": indications and contraindications

The active substance of the drug for injection "Ketonal" is ketoprofen. This component provides anti-inflammatory, analgesic and antipyretic effect.

Indications for the use of this medicinal product:

• limb injuries;
• postoperative period;
• menstrual pain and pain with algomenorrhea;
• arthritis;
• bursitis;
• gout;
• gendenitis.

Ketonal, despite its effectiveness, has a lot of contraindications that you need to pay attention to.

These include:

• non-ulcerative dyspepsia;
• bronchial asthma;
• renal and liver failure;
• history of bleeding;
• children's age (up to 14 years);
• childbirth and the period of breastfeeding;
• individual intolerance to the components of the drug.

"Diclofenac": indications and contraindications

"Diclofenac" is a drug from the NSAID group, a derivative of phenylacetic acid. This drug perfectly relieves pain, swelling, inflammation, and also has an antipyretic effect.

It is used for:

• injuries of the musculoskeletal system;
• neuralgia;
• bursitis;
• radiculitis;
• tendinitis;
• Do not lie;
• arthrosis and spondylarthrosis;
• lumbago;
• rheumatoid arthritis;
• rheumatism;
• ankylosing spondylitis;
• primary dysmenorrhea;
• postoperative period.

Contraindications to injections of the drug "Diclofenac" are:

1. acute rhinitis;
2. bronchial asthma;
3. hives;
4. internal bleeding;
5. dysfunction of the kidneys and liver;
6. peptic ulcer of the stomach and duodenum;
7. third trimester of pregnancy;
8. lecture period;
9. children's age (up to 7 years);
10. individual intolerance.

Injectable analgesics used during labor

During childbirth, the appointment of analgesics should be approached with great responsibility and an injection of painkillers should be given only in case of emergency. In this case, the pain can be so severe that it interferes with the normal opening of the cervix and generally negatively affects labor.

Therefore, it is important to choose a drug that will not only alleviate the suffering of a woman, but also will not harm the fetus. As a rule, injections of such medicines as Promedol, Fentanyl, Dolantin, Petedin, Meperidin are used.

These are very effective remedies, the effect of which occurs within a few minutes, while their concentration is low, so there will be no harm to the health of the mother and child. The introduction is carried out when the cervix is ​​opened at least 5 cm, and only with the consent of the expectant mother.

In order to reduce labor pain, antispasmodic injections can be used. The most famous among them are "Papaverine" and "Drotaverine hydrochloride" ("No-shpa").

Other painkillers in the form of injections

The most powerful painkillers are used in the terminal stage of cancer, when the pain becomes unbearable. As a rule, in this case, the prescription narcotic drug "Morphine hydrochloride" is prescribed.

With pancreatitis, one of the symptoms of which is also severe pain, the drugs "Odeston", "Dicetel", "Mebeverin" are prescribed.