The main groups of analgesics and antipyretics of combined composition. Analgesics. Side effects of AA

Non-narcotic analgesics capable of reducing the activity of the enzyme that causes painful sensations. Most drugs can also have a decongestant effect. After taking non-narcotic energy drinks, the blood vessels dilate, which leads to increased heat transfer. This means that when taking analgesics, body temperature may drop slightly. Some of them are used specifically as antipyretics.

The most popular non-narcotic analgesic drugs are listed below:

1. Analgin is the first medication that comes to mind when you mention analgesics. It is a pyrazolone derivative and is characterized by rapid solubility.

2. Paracetamol is an antipyretic analgesic. Its composition is practically non-toxic. Paracetamol helps to effectively lower the temperature and relieve headaches.

3. Pyramidon is a strong non-narcotic analgesic, which is usually prescribed for rheumatic pain.

4. Citramon and aspirin are another pair of well-known analgesics. The remedies help get rid of headaches of various origins, including pressure.

5. Ibuprofen is a strong pain reliever that can pacify pain of any nature.

Askafen, Asphen, Butadione, Phenacetin, Indomethacin, Naproxen - all these are non-narcotic analgesics, and the list goes on for a long time.

It is not easy to name the most powerful non-narcotic analgesic. Everyone chooses a “standby” analgesic for themselves, depending on the characteristics of the body: for some, to get rid of a headache, an aspirin tablet will be enough, while others have to save themselves with something no weaker than ibuprofen.

The main thing is not to get carried away. It’s one thing if analgesics are taken once every five years “on a special occasion,” and quite another thing when pills are swallowed every day. A specialist will probably be able to suggest a safer solution to the problem, or help you choose the most suitable analgesic.

Non-narcotic analgesics

Non-narcotic analgesics are drugs that reduce the perception of pain without noticeable disruption of other functions of the central nervous system and are devoid (unlike narcotic analgesics) of psychotropic effects (and therefore narcogenicity), a depressing effect on nerve centers, which allows them to be used more widely and for a long time. However, their analgesic effect is significantly weaker, and for pain of a traumatic and visceral nature they are practically ineffective.

In addition to the analgesic effect, drugs in this group have antipyretic and anti-inflammatory effects; many, in therapeutic doses, reduce platelet aggregation and the interaction of immunocompetent cells. The mechanism of action of non-narcotic analgesics is not completely clear, but it is assumed that their effect is based on inhibition of prostaglandin synthesis in various tissues. In the mechanism of action of non-narcotic analgesics, a certain role is played by the influence on the thalamic centers, which leads to inhibition of the conduction of pain impulses in the cerebral cortex. By the nature of the central action, these analgesics differ from narcotic drugs in a number of features (they do not affect the ability of the central nervous system to summation of subcortical impulses).

Inhibition of prostaglandin biosynthesis plays an important role in the mechanism of action of salicylates. They interfere with different links in the pathogenetic chain of inflammation. Characteristic of the action of these drugs is a stabilizing effect on lysosome membranes and, as a result, inhibition of the cellular response to **** irritation, the antibody-antigen complex and the release of proteases (salicylates, indomethacin, butadione). These drugs prevent protein denaturation and have anti-complementary activity. Inhibition of prostaglandin biosynthesis leads not only to a decrease in inflammation, but also to a weakening of the algogenic effect of bradykinin. Non-narcotic analgesics also stimulate the pituitary-adrenal axis, thereby promoting the release of corticoids.

Since the ability to penetrate tissue is different for different drugs, the severity of the above effects varies greatly among them. On this basis, they are divided into analgesics-antipyretics (simple analgesics) and analgesics-antiphlogistics, or non-steroidal anti-inflammatory drugs. Most drugs are weak acids, so they penetrate well into the area of inflammation, where they can concentrate. They are eliminated mainly in the form of inactive metabolites (biotransformation in the liver) with urine, and to a lesser extent with bile.

Analgesic and antipyretic effects develop quickly; anti-inflammatory and desensitizing effect - slower; it requires large doses. At the same time, the risk of developing complications associated with inhibition of prostaglandin synthesis (sodium retention, edema, ulceration, bleeding, etc.), with the direct toxic effect of certain chemical groups on tissue (inhibition of hematopoiesis, methemoglobinemia, etc.), allergic and paraallergic (" aspirin asthma", "aspirin triad") reactions. During pregnancy, prostaglandin synthesis inhibitors can inhibit and delay labor and promote premature closure of the ductus arteriosus. In the first trimester, they are usually not prescribed due to the danger of a pathogenic effect (although most drugs have been proven to lack teratogenicity in animals). In recent years, drugs have appeared that inhibit both cyclooxygenase (synthesis of prostaglandins, thromboxane, prostacyclin) and lipoxygenase (synthesis of leukotrienes), which increases anti-inflammatory activity while eliminating the possibility of paraallergic reactions (vasomotor rhinitis, rashes, bronchial asthma, “aspirin triad”)

A promising direction is the creation of new drugs with relative selectivity for various cyclooxygenases (thromboxane synthetase inhibitor ibutrin (ibufen); PG synthetase inhibitor F2-alpha tiaprofen, which less often causes bronchospasm, stomach ulcers and edema associated with PG F2 deficiency; COX-2 inhibitors nise (nimesulide).

Nonsteroidal anti-inflammatory drugs (NSAIDs)) are used for pain and inflammation of joints and muscles, neuralgia, headaches. As antipyretics, they are prescribed for fever (body temperature above 39 ° C); to enhance the antipyretic effect, they are combined with vasodilators, neuroleptics and antihistamines. Salicylates provoke Reye's syndrome in viral diseases in children under 12 years of age; amidopyrine and indomethacin can cause convulsions, so paracetamol is the antipyretic of choice. In addition to salicylates, drugs of groups 4-8 have high anti-inflammatory and desensitizing activity (see classification). Aniline derivatives lack anti-inflammatory activity; pyrazolone is rarely used as an NSAID, since it inhibits hematopoiesis and has a small breadth of therapeutic action.

Contraindications to the use of NSAIDs are allergic and paraallergic reactions to them, gastric ulcers, diseases of the hematopoietic system, and the first trimester of pregnancy.

Classification of non-narcotic analgesics

I. Derivatives salicylic acid: acetylsalicylic acid (aspirin), sodium salicylate, acelysin, salicylamide, methyl salicylate. Representatives of this group are characterized by low toxicity (LD-50 of acetylsalicylic acid is 120 g), but a noticeable irritant effect (risk of ulceration and bleeding). Drugs in this group are contraindicated in children under 12 years of age.

II. Pyrazolone derivatives: analgin (metamezol), amidopyrine (aminophenazone), butadione (phenylbutazone), antipyrine (phenazone). The drugs have a small breadth of therapeutic action, inhibit hematopoiesis, and therefore are not prescribed for a long time. Analgin, due to its good water solubility, is used intramuscularly, subcutaneously and intravenously for emergency pain relief and treatment of hyperthermia; amidopyrine increases convulsive readiness in young children and reduces diuresis.

III. Para-aminophenol derivatives: phenacetin and paracetamol. Representatives of this group lack anti-inflammatory activity, antiplatelet and anti-rheumatic effects. They practically do not cause ulcer formation, do not inhibit kidney function, and do not increase convulsive activity of the brain. Paracetamol is the drug of choice for the treatment of hyperthermia, especially in children. Phenacetin causes nephritis with long-term use.

IV. Indoleacetic acid derivatives: indomethacin, sulindac, selective COX-2 inhibitor - stodolac. Indomethacin is the standard in terms of anti-inflammatory activity (maximum), but interferes with the exchange of brain mediators (reduces the level of GABA) and provokes insomnia, agitation, hypertension, convulsions, and exacerbation of psychoses. Sulindac turns into indomethacin in the patient's body and has a longer and slower effect.

V. Phenylacetic acid derivatives: diclofenac sodium (ortofen, voltaren). This drug rarely causes ulceration and is used primarily as an anti-inflammatory and antirheumatic agent.

VI. Propionic acid derivatives: ibuprofen, naproxen, pirprofen, tiaprofenic acid, ketoprofen. Ibuprofen is similar to diclofenac; naproxen and pyroprofen provide a greater anti-inflammatory effect; Tiaprofen exhibits greater selectivity in suppressing the synthesis of PG F2-alpha (less likely to have side effects on the bronchi, gastrointestinal tract and uterus).

VII. Derivatives of fenamic (anthranilic) acid: mefenamic acid, flufenamic acid. Mefenamic acid is used mainly as an analgesic and antipyretic; flufenam - as an anti-inflammatory agent (weak analgesic).

VIII. Oxicams: piroxicam, loroxicam (xefocam), tenoxicam, selective COX-2 inhibitor meloxicam. The drugs differ in their duration of action (12-24 hours) and their ability to penetrate well into inflamed tissues.

IX. Various drugs. Selective COX-2 inhibitors - nabulitone, nimesulide (Nise), niflumic acid - are similar in properties to mefenamic acid; highly active COX-2 inhibitors - celecoxib (Celebrex), Viox (difiunizal - a derivative of salicylic acid) - have a prolonged anti-inflammatory and analgesic effect.

A derivative of pyrrolizinecarboxylic acid - ketorolac (ketorol) - has a pronounced analgesic effect.

X. Various means that have an anti-inflammatory effect: dimexide, mephenamine sodium salt, medical bile, bitofyte. These drugs are used topically for pain syndromes in rheumatology and for diseases of the musculoskeletal system.

Pure antipyretics are derivatives of para-aminophenol and salicylic acid. Selective COX-2 inhibitors are used as NSAIDs when there are contraindications to the use of conventional NSAIDs.

17shypnotic substances in veterinary medicine

Sleeping pills
Sleeping pills promote sleep and provide the necessary duration of sleep.
Animals deprived of sleep die within 4–6 days, while without food they can live 2–3 weeks or more.
All sleeping pills are divided into 3 groups:
1. short duration of action (provide the process of falling asleep);
2. average duration actions (promote falling asleep and support sleep in the first hours);
3. long-acting (provide the entire duration of sleep).
Sleeping pills are often used for premedication, enhancing the effect of anesthesia, local anesthetics and analgesics.

Mechanism of action:
Hypnotics have a depressing effect on interneuronal (synaptic) transmission in various formations of the central nervous system (in the cerebral cortex, afferent pathways). Each group of hypnotics is characterized by a specific localization of action.
Drugs with hypnotic activity are classified based on their principle of action and chemical structure:
1. benzodiazepine derivatives;
2. barbituric acid derivatives;
3. aliphatic compounds.
- Benzodiazepine derivatives (nitrazepam, diazepam, phenazepam, etc.)
Their main action is to eliminate mental stress, and the ensuing calm promotes the development of sleep.
They have hypnotic, sedative, anticonvulsant, muscle-relaxing effects.
The hypnotic effect is the result of their inhibitory effect on the limbic system and, to a lesser extent, on the activating reticular formation of the brain stem and cortex.
Muscle relaxation develops as a result of suppression of polysynaptic spinal reflexes.
The anticonvulsant effect is the result of activation of inhibitory processes in the brain, realized through GABA. At the same time, the flow of chlorine ions into neurons increases, which leads to an increase in the inhibitory postsynaptic potential.

Derivatives of barbituric acid.
Depending on the strength and duration of action, barbiturates are conventionally divided into 3 groups:
1. short acting- hexenal, sodium thiopental (used for short-term anesthesia);
2. medium duration of action - barmamil, etaminal sodium, cyclobarbital (sleeping pills). Causes sleep lasting 5 - 6 hours, in large doses - anesthesia (in small animals).
3. long acting
Mechanism of action. Barbiturates inhibit the reticular formation of the midbrain, reduce the excitability of the sensory and motor zones of the cortex, which is due to a decrease in the synthesis of acetylcholine in the axons of neurons and an increase in the release of GABA into the synoptic cleft, which is a mediator of inhibition.
In addition, barbiturates reduce the sodium permeability of neuronal membranes and inhibit the respiration of mitochondria in nervous tissue.
Medium- and long-acting barbiturates are considered true hypnotics.
All barbiturates are white or some shades of crystalline powders, poorly soluble in water, and have acidic properties.
Contraindicated for liver and kidney diseases, sepsis, fever, caesarean section, severe circulatory disorders, respiratory diseases.
The imported drug rompun has become widespread in surgery.
After intramuscular or intravenous administration, depending on the dose, animals experience calmness and sleep with relaxation skeletal muscles and severe anesthesia.

21 NEUROLEPTICS

The antipsychotic effects of neuroleptics vary according to the following: external manifestations:

the depth and duration of the calm they cause;

the severity of activation of human (animal) behavior after using the product;

antidepressant effect.

It goes without saying that preference is given to one drug or another depending on the goals pursued by the doctor. So, for example, if it is necessary to weaken the stress reaction when transporting an animal, there is more hope for drugs with sedative properties, but if it is necessary to smooth out tense ranking conflicts without weakening eating behavior, agents with activating effects are desirable.

The mechanism of action of antipsychotics is complex, and in its explanation it is difficult to determine which changes in the brain are primary and which are secondary. Nevertheless, general patterns have been identified in the action of most drugs in this group.

Neuroleptics, like sedatives, inhibit the reticular formation of the brain stem and weaken its activating effect on the cerebral cortex. In different parts of the central and autonomic nervous system, they selectively interfere with the transmission of excitation along adrenergic, dopaminergic, cholinergic and other synapses and, depending on this, cause certain effects. Thus, the sedative and anti-stress effect can be associated with the blockade of adrenoreactive systems of the reticular formation, the accumulation of the inhibitory mediator - GABA - in the central synapses; antipsychotic - with suppression of dopaminergic processes in the limbic system; autonomic disorders (weakening of gastrointestinal motility and gland secretion) - with weakening or blockade of the transmission of excitation in cholinergic synapses; revival of lactation - with blockade of dopamine receptors of the pituitary gland and the release of prolactin into the blood, etc.

Neuroleptics inhibit the release of corticotropin- and somatotropin-releasing factors by the hypothalamus, and this underlies the mechanism for preventing stress-induced changes in carbohydrate and mineral metabolism in the body.

Neuroleptics, both parenterally and orally, are well absorbed into the blood and penetrate the blood-brain barrier. Most of all they accumulate in the liver, where they undergo transformation, after which they are excreted from the body, unchanged or transformed, mainly through the kidneys.

It is possible to develop allergies to antipsychotics, some of them irritate tissues, with prolonged use they damage the liver (phenothiazine derivatives), cause extrapyramidal disorders (stiffness of movements, trembling of the muscles of the limbs, which is associated with a weakening of the inhibitory influence of the cerebral cortex on the motor centers of the subcortex). However, the danger of these complications in animals is not as significant as in humans, to whom drugs can be prescribed for longer periods, calculated in months.

The group of neuroleptics includes derivatives of phenothiazine, thioxanthene (chlorprothixene), butyrophenone (haloperidol), rauwolfia alkaloids, lithium salts.

Phenothiazine derivatives.

Phenothiazine itself has neither psychotic nor neurotropic properties. Known as an anthelmintic and insecticidal drug. Psychotropic drugs are obtained by introducing various radicals into its molecule at positions 2 and 10.

All phenothiazine derivatives are hydrochlorides and are similar in appearance. These are white with reddish, some (triphthazine, mepazine) crystalline powders with a greenish-yellow tint. Easily soluble in water, 95% alcohol, chloroform, practically insoluble in ether and benzene. Easily oxidize and darken in light. Solutions without stabilizers deteriorate. In case of contact with skin or mucous membranes, they cause severe irritation (weigh or pour from one container to another with rubber gloves and a respirator!). At intramuscular injections Painful infiltrates are possible, and with rapid injection into a vein, damage to the epithelium is possible. Therefore, the drugs are diluted in solutions of novocaine, glucose, and isotonic sodium chloride solution.

Causes photosensitivity in animals; in addition to the neuroleptic effect - muscle relaxation, reduce body temperature; block the trigger zone of the vomiting center and prevent or relieve the development of the emetic effect mediated through this zone (for example, from apomorphine, arecoline, etc.), do not act antiemetic when irritating the vestibular apparatus and gastric mucosa; inhibit the cough center, eliminate hiccups.

Aminazine. White or off-white fine-crystalline powder, easily soluble in water; It is bactericidal, so solutions are prepared using boiled distilled water without subsequent sterilization.

Aminazine has a well-expressed central adrenolytic effect. It blocks impulses coming from extero- rather than from interoreceptors more strongly: it prevents neurogenic gastric ulcers that occur during immobilization and electrical stimulation of rats, but does not affect their development during trauma duodenum; reduces the time between the end of feed intake and the beginning of the ruminant period and prevents the cessation of ruminant cycles in sheep after severe electrical stimulation of the skin. Sensitivity to chlorpromazine is higher in horses than in cattle.

Used orally and intramuscularly: as an anti-stress agent for various manipulations with animals; for premedication and potentiation of the action of analgesics, anesthetics, hypnotics and anticonvulsants; before manipulations to remove blockage of the esophagus in ruminants (in emergency cases, it can be administered intravenously), to reduce dislocated joints; with self-gnawing and hypogalactia in fur-bearing animals; as an antiemetic when deworming dogs with arecoline.

After administration of chlorpromazine to slaughter animals, it is most often found in the lungs, kidneys and liver. Residual amounts remain in the muscles for 12-48 hours.

Levomepromazine (tizercin). It potentiates anesthetics and analgesics more strongly than aminazine, but acts weaker than it as an antiemetic. It acts more on norepinephrine than on dopamine receptors. Side effects less pronounced.

Etaperazine. It is better tolerated and has a stronger antiemetic effect than aminazine, but is less suitable for premedication.

Triftazin. The most active antipsychotic. The sedative effect is stronger than aminazine, and the adrenolytic effect is weaker. Does not have antihistamine, anticonvulsant or antispasmodic effects. It inhibits gastrointestinal motility in ruminants more than in other species. The liver is less affected.

Fluorophenazine decanoate. A drug with moderate sedative effect, blocks dopamine receptors more than norepinephrine receptors. Its antipsychotic effect is combined with an activating one. Of interest for animal testing as long as active antipsychotic(a single injection lasts for 1-2 weeks or more).

Butyrophenone derivatives.

The peculiarity of the pharmacodynamics of drugs in this group is that they have strongly pronounced antipsychotic and stimulating properties, while sedative and hypothermic properties are weaker. More specifically than other neuroleptics, they act on the cerebral cortex, enhancing inhibition processes in it. This is apparently explained by the great similarity of their chemical structure to GABA, the inhibitory transmitter of the cerebral cortex. The main disadvantage is the possibility of extrapyramidal disorders. However, these disorders occur from large doses. Studies have shown that butyrophenones (haloperidol) are promising for use in veterinary medicine as anti-stress and promoting the growth of young animals. The latter is apparently due to the well-pronounced energizing properties of butyrophenones.

Haloperidol. One of the most active antipsychotics (stronger even than triftazine), which is characterized by sedative and central adrenolytic effects (especially on dopamine receptors) in the absence of central and peripheral effects on cholinergic receptors, low toxicity.

Approximate doses (mg/kg body weight): 0.07-0.1 orally and 0.045-0.08 intramuscularly to prevent transport stress in calves.

Of other butyrophenones, trifluperidol (its psychotic effect is more active than haloperidol) and droperidol (acts strongly, quickly, but does not last long) are of interest.

Rauwolfia alkaloids.

Extracts from the roots and leaves of the rauwolfia plant have long been used as sedatives and antihypertensives in Indian folk medicine. Rauwolfia is a perennial shrub of the Kutrov family, grows in the South and South-East Asia(India, Sri Lanka). The plant, especially in the roots, contains a large amount of alkaloids (reserpine, ajmalicine, serpine, etc.), which act sedatively, hypotensively (reserpine) or adrenolytically (ajmalicine, etc.).

Under the influence of rauwolfia alkaloids, especially reserpine, animals calm down, physiological sleep deepens, and interoreceptive reflexes are inhibited. The hypotensive effect is quite strong, and therefore the drugs are widely used in medicine for hypertension. The hypotensive effect develops gradually, maximally after a few days.

Unlike aminazine, reserpine (one of the main alkaloids of rauwolfia) does not have an adrenolytic effect and, at the same time, causes a number of cholinomimetic effects: slowing down cardiac activity, increasing gastrointestinal motility, etc. It does not have a ganglion-blocking effect.

Of the mechanisms of action, disruption of the process of norepinephrine deposition is important; its release from the presynaptic endings of adrenergic nerves is accelerated. In this case, the mediator is quickly inactivated by monoamine oxidase and its effect on peripheral organs is weakened. Reserpine does not appear to affect the reuptake of norepinephrine. Reserpine reduces the content of norepinephrine, dopamine and serotonin in the central nervous system, since the transport of these substances from the cellular plasma is blocked and they are deaminated. As a result, reserpine has a depressant effect on the central nervous system. Animals become less active and react weaker to exogenous stimuli. The effect of sleeping pills and narcotic substances increases.

Under the influence of reserpine, the content of catecholamines in the heart, blood vessels and other organs decreases. As a result, cardiac output decreases, total peripheral resistance blood vessels and arterial blood pressure. Most authors deny the effect of reserpine on the vasomotor center. Along with a decrease in blood pressure, kidney function improves: blood flow increases and glomerular filtration increases.

Secretion and motility of the gastrointestinal tract increase. This is due to the predominant influence of the vagus nerve and local irritating effect, which manifests itself with prolonged use of the drug.

Reserpine reduces body temperature, which is apparently explained by a decrease in serotonin content in the hypothalamus. In dogs and cats it causes constriction of the pupils and relaxation of the nictitating membrane. There is also some information about the inhibitory effect on the gonads in animals.

Drugs in this group are used as sedatives and antihypertensives for stress and other neuropsychic disorders, hypertension, mild forms of heart failure, and thyrotoxicosis.

Side effects usually occur with long-term use of drugs and are manifested by drowsiness, diarrhea, increased blood clotting, bradycardia, and fluid retention in the body. These phenomena are relieved by atropine.

Reserpine. The ester breaks down in the body into reserpic acid, which is an indole derivative, and other compounds. White or yellowish finely crystalline powder, very slightly soluble in water and alcohol, highly soluble in chloroform. The most active drug has a more pronounced local irritant effect.

Cattle are very sensitive to it, so when administered intravenously, the dose should not exceed 7 mg per animal. Horses are also sensitive to reserpine, and a dose of 5 mg parenterally causes severe colic. Dogs and cats tolerate higher doses of reserpine - 0.03-0.035 mg/kg live weight.

Used for prevention and treatment of stress, neuroses, hypertension, thyrotoxicosis. Contraindicated in severe cardiovascular diseases, insufficient renal function, gastric and duodenal ulcers,

Carbidine. Indole derivative. White crystalline powder, easily soluble in water, very slightly soluble in alcohol; pH of solutions is 2.0-2.5. It has neuroleptic, antipsychotic activity and moderate antidepressant effects. Possible side effects: stiffness, tremor, hyperkinesis, which can be relieved with cyclodol.

Used for nervous disorders, it can be used to prevent stress, in medicine for schizophrenia and alcoholic psychoses. Contraindicated in case of liver dysfunction, drug poisoning and analgesics.

Lithium salts.

Lithium is an element from the group of alkali metals, widely distributed in nature, found in small quantities in the blood, organs and muscles of animals. Lithium salts have long been used in medicine to treat gout and dissolve kidney stones. In the early 50s, it was found that lithium drugs have a sedative effect on mental patients and prevent attacks of schizophrenia. In this regard, lithium preparations are classified as new group substances with a calming effect - mood stabilizers. They are able to normalize the functions of the central nervous system and are active in both depression and agitation.

The pharmacodynamics of the drugs is simple. They are quickly absorbed after oral administration and distributed depending on the blood supply to organs and tissues. In the body they dissociate into ions, which can be detected in various organs and tissues 2-3 hours after administration of the drug. Lithium is excreted primarily by the kidneys, and excretion depends on the content of sodium and potassium ions in the blood. With a lack of sodium chloride, lithium retention occurs, and with increased administration, lithium excretion increases. Lithium can cross the placenta and be excreted in milk.

The mechanism of the psychotropic action of lithium is explained by two theories: electrolyte and neurotransmitter. According to the first, lithium ions affect the transport of sodium and potassium ions in the nervous and muscle cells, and lithium is a sodium antagonist. According to the second, lithium increases the intracellular deamination of norepinephrine, reducing its content in brain tissue. In large doses, it reduces the amount of serotonin. In addition, the brain's sensitivity to neurotransmitters changes. The effect of lithium on healthy and sick people is different, so there is conflicting information in the literature.

The pharmacodynamics of lithium have been studied in laboratory animals and humans.

Compared to aminazine, lithium has a milder and longer-lasting effect on the nervous system, but is weaker. Lithium does not increase the sensitivity threshold and does not suppress the defensive reflex, reduces motor activity and research activity. Lithium hydroxybutyrate inhibits the transmission of excitation from the afferent pathways of the brain, while blocking the flow of pain impulses from the periphery to the central nervous system. The drugs prevent the manifestation of the stimulating effect of various stimulants on the central nervous system and at the same time reduce depression.

Related information.

Analgesic-antipyretics (AAs) are among the most commonly used drugs in the world. The leading place in sales is occupied by over-the-counter drugs (OTC drugs, over-the-counter, OTC-AA): acetylsalicylic acid, ibuprofen, metamizole, paracetamol. These analgesics are used for the symptomatic treatment of headache, toothache, dysmenorrhea, fever, etc.

Both the therapeutic and side effects of AA are associated with inhibition of a key enzyme in arachidonic acid metabolism, cyclooxygenase (COX). As a result of this metabolism, under the influence of COX, prostaglandins are formed from arachidonic acid, and under the influence of another enzyme, lipoxygenase, leukotrienes are formed (Fig.). Prostaglandins are the main mediators of inflammation, because they:

sensitize nerve endings to the action of other inflammatory mediators (histamine, bradykinin, etc.);
increase vascular permeability and cause vasodilation, which leads to the development of local vascular reactions;
are chemotaxis factors for a number of immunocompetent cells, which contributes to the formation of inflammatory exudates;
increase the sensitivity of the hypothalamic thermoregulation center to the pyrogenic effect of interleukin-1, which leads to the development of a febrile reaction.

Prostaglandins are not only involved in the process of inflammation as one of its mediators, but also play an important role in the functioning of the gastrointestinal tract, of cardio-vascular system, kidneys and other vital organs and systems. By inhibiting the biosynthesis of prostaglandins, AA not only lead to a decrease in the inflammatory or pain response, but also to the development of adverse reactions from these systems. Not so long ago, reports began to appear about another property of AA - their antitumor activity. Thus, a reduction in the risk of developing carcinoma of the rectum and esophagus has been shown with regular long-term use of Aspirin.

Currently, there are three isoforms of COX - COX-1, COX-2 and COX-3. COX-1 is constitutive, has the functional activity of a structural enzyme, is constantly present in cells, catalyzing the formation of prostaglandins that regulate physiological functions in various organs, for example, in the mucous membrane of the stomach and bronchi, in the kidneys. COX-2 is an inducible isoform because it begins to function and its content increases during inflammation. COX-2 levels are low under normal conditions and increase under the influence of cytokines and other anti-inflammatory agents. It is believed that it is COX-2 that takes part in the synthesis of “pro-inflammatory” prostaglandins, potentiating the activity of inflammatory mediators, such as histamine, serotonin, bradykinin. In this regard, it is assumed that the anti-inflammatory effect of AA is due to the inhibition of COX-2, and the adverse reactions are due to COX-1. COX-3 functions in the structures of the central nervous system. Studies have shown that the activity of this enzyme is inhibited by antipyretic drugs, such as paracetamol, phenacetin, antipyrine, analgin. Thus, COX-3 inhibition may represent a major central mechanism by which these drugs reduce pain and possibly fever.

The developed selective COX-2 inhibitors have significantly fewer side effects than non-selective AA, but they are not over-the-counter drugs. Paracetamol has a fundamentally different mechanism of action than other OTC-AAs, which even in small doses selectively inhibits the COX-3 isoform in the structures of the central nervous system and does not affect COX in peripheral tissues, which distinguishes this drug from other AA in terms of its therapeutic safety profile and side effects. In particular, the drug does not have an ulcerogenic effect, does not provoke the development of bronchospasm, does not provide antiplatelet or tocolytic effects, but it has virtually no anti-inflammatory effect.

Side effects of AA

AA have a number of reliably recorded side effects:

ulcerogenic;
hematotoxic;
allergic;
Reye's syndrome;
hepatotoxic;
influence on the cardiovascular and respiratory systems.

The relative risk of developing side effects of AA varies (Table 1). As follows from the table, paracetamol has the lowest risk of side effects. Metamizole most often causes the development of agranulocytosis, which led to a ban on its use in most countries of the world. Usually among the side effects of AA, the first place in frequency of occurrence is occupied by ulcers of the gastrointestinal tract (primarily the stomach) and bleeding from them. According to gastroscopy, the incidence of ulceration of the gastrointestinal tract after taking AA can reach 20%.

The development of the ulcerogenic effect of AA is associated with the suppression of the activity of COX-2, localized in the mucous membrane of the gastrointestinal tract. As a result, prostaglandin biosynthesis is reduced, leading to decreased bicarbonate and mucus production and increased secretion and reverse diffusion of hydrogen ions. These side effects most often occur in patients at risk:

taking AA for a long time or taking large doses of these drugs;
having a history of peptic ulcer disease;
over 60 years old;
simultaneously receiving glucocorticoids or anticoagulants;
infected H. pylori;
having severe concomitant diseases (for example, congestive heart failure);
alcohol abusers.

The developed rapidly soluble or enteric forms of acetylsalicylic acid were supposed to reduce the incidence of ulcers of the gastrointestinal tract. However, clinical trials have not revealed a significant reduction in the incidence of this side effect. Probably, the observed result is associated with inhibition of COX in the mucous membranes of the gastrointestinal tract, not only during the local action of AA, but during their persistence in the blood.

The most severe complication when using OTC-AA is hematotoxicity. The use of metamizole increases the risk of developing agranulocytosis by 16 times. Therefore, its use is prohibited in more than 20 countries around the world. However, the drug is still used in the Russian Federation. However, there is an opinion that the risk of developing metamizole-induced agranulocytosis is exaggerated, and the most serious side effect of this drug is its cardiotoxic effect.

A rare but serious side effect when using acetylsalicylic acid is Reye's syndrome. It is characterized by severe encephalopathy and fatty liver degeneration. It usually occurs in children (with a peak incidence at 6 years of age) after previous viral infections. With the development of Reye's syndrome, there is a high mortality rate, which can reach 50%.

Effect on the cardiovascular system

Numerous studies have found that short-term use of AA does not pose a significant risk of developing hypertension or an increase in cardiovascular disease in healthy individuals. However, the use of all AA, except paracetamol, significantly increases the risk of developing heart failure in patients with arterial hypertension and the elderly.

All OTC-AAs, except paracetamol, affect blood clotting, but this effect is variable. Aspirin is more selective for COX-1 than for COX-2, so in low doses it selectively inhibits the formation of thromboxane A 2 without affecting the biosynthesis of prostaglandin I 2 . In addition, unlike other AA, Aspirin is more selective towards platelet COX-1. Its action in small doses is based on the selective inhibition of thromboxane synthesis, which, accordingly, reduces platelet aggregation. Thanks to this property, Aspirin significantly reduces the likelihood of developing sudden cardiac death, myocardial infarction and stroke among patients at risk.

Unlike Aspirin, other “traditional” AA inhibit both COX-1 and COX-2, i.e., the biosynthesis of both thromboxane A 2 and prostaglandin I 2 . The effect of these drugs on the prevention of thrombosis has not been established.

By blocking the biosynthesis of prostaglandins in the kidneys, all OTC-AAs, except paracetamol, affect water-electrolyte balance and may have a hypertensive effect. In addition, due to the effect on the renal biosynthesis of prostaglandins, the likelihood of interaction of AA with β-blockers, diuretics, ACE inhibitors and other antihypertensive drugs increases sharply.

Influence at respiratory system

The effect on the respiratory system of AA is observed in individuals with the so-called. aspirin variant of bronchial asthma. The pathogenesis of the disease is associated with inhibition of bronchial COX-2 under the influence of all OTC-AAs, except paracetamol. As a result, the biosynthesis of leukotrienes increases, causing the development of attacks of expiratory dyspnea. This effect is most pronounced with acetylsalicylic acid. The disease is characterized by a triad of symptoms:

polypous rhinosinusitis;
attacks of suffocation;
intolerance to non-steroidal anti-inflammatory drugs (NSAIDs).

Aspirin-induced asthma can be combined with atopic asthma, but it can also occur in isolation. Most often this disease occurs between the ages of 30-50 years. Women get sick more often than men. The incidence of aspirin-induced asthma can reach 40% of bronchial asthma diseases.

Adverse reactions from the skin

Nonsteroidal anti-inflammatory drugs can cause or worsen psoriasis. However, there is no clear connection between the use of Aspirin and the occurrence of psoriasis and psoriatic arthritis. However, long-term use of paracetamol and other AA (with the exception of Aspirin) may increase the risk of developing psoriasis and psoriatic arthritis.

In addition, negative reactions are common when using AA in the form of urticaria/Quincke's edema, although these reactions to paracetamol are quite rare.

Use of AA during pregnancy

Classic non-selective COX inhibitors, including Aspirin, do not increase the risk birth defects development in the human body. However, their use in the second half of pregnancy may affect pregnancy and the fetus due to the fact that prostaglandin inhibitors have vascular effects, in particular, they can cause narrowing of the fetal ductus arteriosus and a decrease in renal blood flow. Therefore, treatment with COX inhibitors should be stopped at 32 weeks of pregnancy. The ability of AA to inhibit ovulation and induce miscarriage is still under debate.

The safest analgesic for pregnant women is paracetamol.

Compared to other AA, paracetamol has the widest range of therapeutic safety and the fewest side effects. It does not cause ulcer formation, does not have a tocolytic effect, does not affect the cardiovascular system, does not inhibit bone marrow hematopoiesis, does not cause the development of bronchospasm, is well tolerated during pregnancy, allergic reactions occur rarely. However, paracetamol has side effects that are not typical for other AAs. This is a hepatotoxic effect that occurs during an overdose of the drug, due to the fact that it does not have time to bind to glucuronic acid.

Due to the widest therapeutic safety profile of paracetamol, it is the drug of first choice in the treatment of febrile conditions in children. It is prescribed in a single dose of 10-15 mg/kg and a daily dose of up to 60 mg/kg.

In general, OTC-AA is usually characterized by the presence of large quantity drug interactions (Table 2). Paracetamol has the least number of drug interactions, and acetylsalicylic acid has the most. Its main interactions are associated with changes in urine pH, which leads to impaired elimination of many drugs.

Dosages used, drug selection algorithm

As follows from the data presented in the article, paracetamol can be considered as the drug of first choice as an antipyretic OTC-NSAID, since this drug is less likely to cause side effects than other drugs in this group, which is due to the peculiarities of its mechanism of action ( selective inhibition of COX in the CNS). In addition, the drug has the least number of drug interactions and can be used even in childhood.

In recent years, there has been a revision of the commonly used doses of paracetamol. Traditionally, in adults the drug is prescribed in a dose of 500-650 mg per 1 dose per os, 3-4 doses per day. However, the results of a study conducted on 500 patients were recently reported. It has been shown that a single dose of 1 g of the drug is more effective than 650 mg. At the same time, when the drug was prescribed 4 times a day, the incidence of side effects was the same. Thus, the following paracetamol dosage regimen can be recommended: 1 g per dose, 4 doses per day.

If the use of paracetamol is ineffective or intolerant, the next drug of choice among OTC-AAs is ibuprofen. Many studies have shown that the safety and effectiveness of ibuprofen is comparable to that of newer AA (coxibs), especially when used long-term (more than 6 months). Additionally, for mild to moderate pain, ibuprofen was often more effective than paracetamol as both an analgesic and an antipyretic. Usually in adults the drug is used in a dose of 400-600 mg per os 3-4 times a day.

If ibuprofen is ineffective or intolerable, acetylsalicylic acid or metamizole is prescribed orally at a dose of 500-1000 mg 2-3 times a day or 250-500 mg 2-3 times a day, respectively.

Literature

Lipsky L. P., Abramson S. B., Crofford L. et al. The classification of cyclooxygenase inhibitors // J Rheumatol. 1998; 25: 2298-2303.
Vane J.R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs // Nature New Biol. 1971; 231: 232-235.
Weissmann G. Prostaglandins as modulators rather than mediators of inflammation // J. Lipid Med. 1993; 6: 275-286.
DuBois R. N., Abramson S. B., Crofford L. et al. Cyclooxygenase in biology and disease // PASEB J. 1998; 12: 1063-1073.
Suthar S. K., Sharma N., Lee H. B., Nongalleima K., Sharma M. Novel dual inhibitors of nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (COX 2): synthesis, in vitro anticancer activity and stability studies of lantadene-non steroidal anti-inflammatory drug (NSAID) conjugates // Curr Top Med Chem. 2014; 14 (8): 991-10-04.
Li P., Cheng R., Zhang S. Aspirin and esophageal squamous cell carcinoma: bedside to bench // Chin Med J (Engl). 2014; 127(7):1365-1369.
Schrör K., Rauch B. Aspirin in primary and secondary prevention of colorectal carcinomas // Med Monatsschr Pharm. 2013, Nov; 36 (11): 411-421.
Sturov N.V., Kuznetsov V.I. Clinical and pharmacological characteristics of NSAIDs for a general practitioner // Zemsky Doctor. 2011. No. 1. P. 11-14.
Chandrasekharan N. V., Dai H., Roos K. L., Evanson N. K., Tomsik J., Elton T. S., Simmons D. L. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression // Proc. Natl. Acad. Sci. USA. 2002, Oct 15; 99 (21): 13926-13931. Epub. 2002, Sep 19.
Gorchakova N. A., Gudivok Ya. S., Gunina L. M. and others. Pharmacology of sports. K.: Olympus. l-ra. 2010. 640 p.
Rainsford K., Willis C.
Roth S. H., Bennett R. E. Non steroidal anti-inflammatory drug gastropathy: recognition and response // Arch Int Med. 1987; 147:2093-2100.
Martinez C., Weidman E. 11th Int Conf Pharmacoepid. 1995.
Rainsford K., Willis C. Relationship of gastric mucosal damage induced in pigs by antiinflammatory drugs to their effects on prostaglandin production // Dig. Dis. Sci. 1982; 27: 624-635.
Kukes V. G., Sychev D. A. Clinical pharmacology of non-narcotic analgesics // Klin. Pharmacol. ter. 2002. No. 5. P. 1-5.
Jasiecka A., Ma?lanka T., Jaroszewski J. J. Pharmacological characteristics of metamizole // Pol J Vet Sci. 2014; 17 (1): 207-214.
Weissmann G. Aspirin // Sci. Am. 1991; 264: 84-90.
Page J., Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem // Arch Int Med. 2000; 160; 777-784.
Khatchadourian Z. D., Moreno-Hay I., de Leeuw R. Nonsteroidal anti-inflammatory drugs and antihypertensives: how do they relate? // Oral Surg Oral Med Oral Pathol Oral Radiol. 2014, Jun; 117(6):697-703.
Antiplatelet Trialists’ Collaboration: Secondary prevention of vascular disease by prolonged antiplatelet treatment // Br Med J. 1988; 296: 320-331.
Kowalski M. L., Makowska J. S. Aspirin-dependent respiratory diseases. Modern approaches to diagnosis and treatment // Allergy Clin. Immunol. Int. J. World Allergy Org. Russ. Ed. 2007. V. 2. No. 1. P. 12-22.
Wu S., Han J., Qureshi A. A. Use of Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Aceta-minophen (Paracetamol), and Risk of Psoriasis and Psoriatic Arthritis: A Cohort Study // Acta Derm Venereol. 2014, Apr 2. doi: 10.2340/00015555-1855.
Graham G. G., Scott K. F., Day R. O. Tolerance of paracetamol // Drug Saf. 2005; 28 (3): 227-240.
Østensen M. E., Skomsvoll J. F. Anti-inflammatory pharmacotherapy during pregnancy // Expert Opin Pharmacother. 2004, Mar; 5 (3): 571-580.
Keith G. Hepatotoxicity of nonnarcotic analgesics // Amer. J. Med. 1998, 1 C, 13 S-19 S.
WHO. Pharmaceutical Newsletter, 1999, 5-6.
McQuay H. J., Edwards J. E., Moore R. A.// Am J Ther. 2000; 9: 179-187.
Protocol No. 4 of the Ministry of Health of the Russian Federation dated October 9, 2000.
Rainsford K. D. Ibuprofen: pharmacology, efficacy and safety // Inflammofarmacol. 2009.

Yu. B. Belousov*, 1,doctor medical sciences, professor, corresponding member of the Russian Academy of Sciences
K. G. Gurevich**,Doctor of Medical Sciences, Professor
S. V. Chausova*, Candidate of Medical Sciences

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Course work

on the topic: Analgesics-antipyretics

Introduction

1.1 Non-narcotic analgesics

1.2 Narcotic analgesics

2.2 Analysis of the range of analgesics and antipyretics in pharmacies

Conclusion

Bibliography

Applications

Introduction

Relevance: Analgesics, or analgesics, are drugs that have the specific ability to weaken or eliminate the feeling of pain, i.e. drugs, the dominant effect of which is analgesia, which is not accompanied in therapeutic doses by switching off consciousness and severe impairment of motor functions.

Based on the chemical nature, nature and mechanisms of pharmacological activity, modern analgesics are divided into two main groups: non-narcotic and narcotic analgesics.

Pain is a protective reaction of the body, a signal of danger, the role of which is very important for a person. The complete absence of pain can be as dangerous as the pain itself. However, severe and prolonged pain can cause damage to vital body systems and even lead to shock.

Pain treatment is quite challenging task, due to the diversity of its causes and the subjectivity of sensations. Currently, pharmaceutical companies produce a huge number of painkillers, often differing only by trade name, while their analgesic effect may be practically the same from each other.

Narcotic analgesics have a strong pain-relieving effect. At the same time, these drugs have quite serious side effects, in particular they can cause addiction with all the ensuing problems of a physiological, psychological and social nature. Non-narcotic analgesics have a less pronounced analgesic effect, but do not cause addiction or withdrawal symptoms, which is why they are more widely used in medical practice.

Purpose of work: Search, analyze, summarize necessary information on this topic; analyze the range of drugs in the group of analgesics and antipyretics.

Study specialized literature on this topic.

To analyze the range of analgesics and antipyretics registered in the Russian Federation.

To analyze the range of analgesics and antipyretics in pharmacies.

Subject of research: structure of the range of drugs of the analgesic-antipyretic group.

Research methods:

scientific-theoretical;

analytical;

observation;

comparison.

1. General characteristics of analgesics

1.1 Non-narcotic analgesics.

Pain occurs when pain receptors (nociceptors) are stimulated. These are the endings of afferent nerve fibers located in the skin, mucous membranes, muscles and internal organs. Pain mediators (peptides that are synthesized in the body) play an important role in the transmission of pain impulses: substance P; somatostatin; cholecystokinin.

The path of the pain impulse: 1. Nociceptor > 2. Afferent nerve fiber> 3. Posterior horns of the spinal cord (interneurons) > 4. Medulla oblongata > 5. Midbrain > 6. Reticular formation> 7. Hypothalamus > 8. Thalamus > 9. Limbic system > 10. Cerebral cortex.

All these structures involved in the perception, generation and conduction of pain impulses form the nociceptive system.

There is a system in the body that has analgesic ability, this is the antinociceptive system, which is represented by endopeptids (endoopiates): enkephalins; endorphin; neoendorphin; dynorphin.

They interact with opiate receptors, and pain in the body is suppressed (a process of inhibition of perception and conduction of impulses in the central nervous system occurs).

The main difference between the group of non-narcotic drugs and the group of narcotic analgesics is the absence of narcotic action, which is reflected in their name. Non-narcotic analgesics are not effective for severe pain. Indications for their use are mainly pain caused by the inflammatory process (myositis, arthritis, neuritis, etc.).

Non-narcotic analgesics, unlike narcotic ones, are characterized by the following basic properties:

1. Analgesic activity manifests itself in certain types of pain: mainly in neuralgic, muscle, joint pain, headaches and toothaches. For severe pain associated with injuries, abdominal surgeries are ineffective.

2. Antipyretic effect, manifested when feverish conditions, and anti-inflammatory effects are expressed to varying degrees in different drugs.

3. No inhibitory effect on breathing and cough centers.

4. Absence of euphoria and phenomena of mental and physical dependence when using them.

Non-narcotic analgesics have analgesic, anti-inflammatory and antipyretic effects. The mechanisms of manifestation of these effects are currently associated with the ability of non-narcotic analgesics to inhibit the activity of the cyclooxygenase enzyme, as a result of which the synthesis of prostaglandins is reduced. Prostaglandins are biological active substances, of which there are several varieties in the body. They are products of arachidonic acid metabolism and play an important role in the regulation of many body functions. At the same time, prostaglandins are mediators of inflammation, that is, their content specifically increases in areas of inflammation. A decrease in the synthesis of prostaglandins during inflammation under the influence of non-narcotic analgesics leads to a decrease in pain impulses from the site of inflammation and a decrease in the intensity of inflammatory phenomena. The antipyretic effect of non-narcotic analgesics is also due to the inhibition of the synthesis of prostaglandins of a certain class, which are pyrogenic, that is, causing an increase in temperature. A decrease in temperature under the influence of non-narcotic analgesics occurs due to an increase in heat transfer (dilation of blood vessels in the skin, increased sweating). At the same time, on normal temperature they do not affect the body.

Classification

Non-narcotic analgesics are classified according to their chemical structure:

1. Salicylic acid derivatives: acetylsalicylic acid (aspirin), lysine acetylsalicylate (acelysin), sodium salicylate, methyl salicylate, salicylamide.

2. Pyrazolone derivatives: amidopyrine, metamizole sodium (analgin), phenylbutazone (butadione).

3. Aniline derivatives: paracetamol.

4. Derivatives of organic acids: phenylpropionic acid - ibuprofen, naproxen, ketoprofen; phenylacetic - diclofenac sodium (ortofen, voltaren); indoleacetic - indomethacin (metindol), sulindac; Anthranilic - mefenamic acid.

5. Oxicams: piroxicam, tenoxicam.

Some non-narcotic analgesics are often called analgesics-antipyretics, since they have not only an analgesic, but also an antipyretic effect. These include derivatives of pyrazolone (analgin), salicylic acid (acetylsalicylic acid) and aniline (paracetamol, phenacetin). These drugs have weak anti-inflammatory properties. However, non-narcotic analgesics with analgesic, antipyretic, anti-inflammatory and desensitizing effects have recently become widely used. Due to their pronounced anti-inflammatory effect, these drugs are called “non-steroidal anti-inflammatory drugs” (NSAIDs). They have found not only application as analgesic and antipyretic agents, but are also widely used in the treatment of various inflammatory diseases.

Indications for use.

Indications for the use of non-narcotic analgesics:

1. Rheumatism and rheumatic joint diseases (rheumatoid arthritis, ankylosing spondylitis).

2. Non-rheumatic diseases of the spine, joints and muscles (osteochondrosis, osteoarthritis, myositis, tendovaginitis).

3. Traumatic injuries to the musculoskeletal system (bruises, sprains, torn ligaments).

4. Neurological diseases of inflammatory and traumatic nature (neuralgia, radiculoneuritis, lumbago).

5. Pre- and postoperative analgesia.

6. Acute pain syndrome of spastic origin (renal, hepatic colic).

7. Various pain syndromes (headache, toothache, dysmenorrhea).

8. Fever.

Non-narcotic analgesic drugs.

Salicylic acid derivatives: acetylsalicylic acid (aspirin), sodium salicylate, acelysin, salicylamide, methyl salicylate. Representatives of this group are characterized by low toxicity, but a noticeable irritant effect (risk of ulceration and bleeding). Drugs in this group are contraindicated in children under 12 years of age.

Pyrazolone derivatives: analgin (metamizole), amidopyrine (aminophenazone), butadione (phenylbutazone), antipyrine (phenazone). The drugs have a small breadth of therapeutic action, inhibit hematopoiesis, and therefore are not prescribed for a long time. Analgin, due to its good water solubility, is used intramuscularly, subcutaneously and intravenously for emergency pain relief and treatment of hyperthermia; amidopyrine increases convulsive readiness in young children and reduces diuresis.

Para-aminophenol derivatives: phenacetin and paracetamol. Representatives of this group lack anti-inflammatory activity, antiplatelet and anti-rheumatic effects. They practically do not cause ulcer formation, do not inhibit kidney function, and do not increase convulsive activity of the brain. Paracetamol is the drug of choice for the treatment of hyperthermia, especially in children. Phenacetin causes nephritis with long-term use.

Indoleacetic acid derivatives: indomethacin, sulindac, selective COX-2 inhibitor - stodolac. Indomethacin is the standard in terms of anti-inflammatory activity (maximum), but interferes with the exchange of brain mediators (reduces the level of GABA) and provokes insomnia, agitation, hypertension, convulsions, and exacerbation of psychoses. Sulindac turns into indomethacin in the patient's body and has a longer and slower effect.

Phenylacetic acid derivatives: diclofenac sodium (ortofen, voltaren). This drug rarely causes ulceration and is used primarily as an anti-inflammatory and antirheumatic agent.

Propionic acid derivatives: ibuprofen, naproxen, pirprofen, tiaprofenic acid, ketoprofen. Ibuprofen is similar to diclofenac; naproxen and pyroprofen provide a greater anti-inflammatory effect; Tiaprofen exhibits greater selectivity in suppressing the synthesis of PG F2-alpha (less likely to have side effects on the bronchi, gastrointestinal tract and uterus).

Derivatives of fenamic (anthranilic) acid: mefenamic acid, flufenamic acid. Mefenamic acid is used mainly as an analgesic and antipyretic; flufenam - as an anti-inflammatory agent (weak analgesic).

Oxicams: piroxicam, loroxicam (xefocam), tenoxicam, selective COX-2 inhibitor meloxicam. The drugs differ in their duration of action (12-24 hours) and their ability to penetrate well into inflamed tissues.

A derivative of pyrrolysine carboxylic acid, ketorolac (ketorol), has a pronounced analgesic effect.

Various drugs. Selective COX-2 inhibitors - nabulitone, nimesulide (Nise), niflumic acid - are similar in properties to mefenamic acid; highly active COX-2 inhibitors - celecoxib (Celebrex), Viox (difiunizal - a derivative of salicylic acid) - have a prolonged anti-inflammatory and analgesic effect.

1.2 Narcotic analgesics

General characteristics and features of the action.

Narcotic analgesics are drugs that suppress pain and, with repeated administration, cause physical and mental dependence, i.e. drug addiction

Narcotic analgesics, unlike non-narcotic ones, are characterized by the following basic properties:

1. Strong analgesic activity, which makes it possible to use them as highly effective painkillers in various fields of medicine, especially for injuries and diseases accompanied by severe pain;

2. A special effect on the human central nervous system, expressed in the development of euphoria and the appearance of physical and mental dependence syndromes with repeated use;

3. Development of a painful syndrome - abstinence in persons with a developed syndrome of physical and mental dependence when deprived of an analgesic drug.

Mechanism of action and pharmacological effects.

The mechanism of action of narcotic analgesics is due to their interaction with opiate receptors, which play an inhibitory role. When interacting with them, the interneuronal transmission of pain impulses to different levels nervous system. In this case, narcotic analgesics imitate the effect of endopioids, which leads to inhibition of the release of pain mediators into the synaptic cleft and their interaction with nociceptors, resulting in analgesia. The strength of analgesia is proportional to the affinity of the narcotic analgesic for opiate receptors.

The pharmacological effects when taking narcotic analgesics are determined by their mechanisms of action and are as follows: in addition to the analgesic effect, all narcotic analgesics to one degree or another have a hypnotic effect, suppress breathing and the cough reflex, increase the tone of the intestines and bladder, cause dyspeptic disorders (nausea, vomiting), central nervous system disorders (hallucinations) and other side effects.

Classification.

In terms of the severity of the analgesic effect and side effects, different drugs from the group of narcotic analgesics differ from each other, which is due to the characteristics of their chemical structure and physical and chemical properties and, accordingly, with the interaction with receptors involved in the implementation of their pharmacological effects.

Classification of narcotic analgesics:

1. Agonists: opium, morphine, promedol, fentanyl, omnopon, codeine, methadone.

2. Agonists - antagonists (partial agonists): pentazocine, nalorphine.

3. Antagonists: naloxone.

By sources of receipt and chemical structure Modern narcotic analgesics are divided into 3 main groups:

1. Natural alkaloids - morphine and codeine, contained in poppy somniferum (Papaver somniferum) in their native state.

2. Semi-synthetic compounds obtained by chemical modification of the morphine molecule - ethylmorphine, etc.

3. Synthetic compounds obtained by complete chemical synthesis and having no analogues in nature - promedol, tramadol, fentanyl, etc.

Based on the chemical structure of the main part of the molecule, narcotic analgesics are divided into 4 main groups:

1. Derivatives of phenanthrene isoquinoline (morphinan) and structurally similar compounds.

2. Derivatives of phenylpiperidine and N-propylphenylpiperidine.

3. Cyclohexane derivatives.

4. Acyclic (derivatives of diphenylethoxyacetic acid and similar in structure).

Indications for use

Indications for the use of narcotic analgesics are:

1. Prevention of painful shock during myocardial infarction; acute pancreatitis; peritonitis; burns, mechanical injuries.

2. For premedication, in the preoperative period.

3. For pain relief in the postoperative period (if non-narcotic analgesics are ineffective).

4. Pain relief in cancer patients.

5. Attacks of renal and hepatic colic.

6. For pain relief during labor.

7. For neuroleptanalgesia (a type of general anesthesia with preservation of consciousness).

Contraindications:

8. Children under three years of age and elderly people (due to respiratory depression). analgesic antipyretic Russian pharmaceutical

9. Traumatic brain injuries (due to respiratory depression and increased intracranial pressure)

10. For “acute” abdomen.

Narcotic analgesic drugs

Most synthetic and semi-synthetic drugs are obtained by chemical modification of the molecule of the ancestor of the group of narcotic analgesics - morphine, preserving elements of its structure or simplifying it.

Morphine is obtained from opium. Opium is the dried milky juice of the unripe pods of the sleeping pill poppy. The active principles of opium are alkaloids, of which there are up to 20 in opium. Opium alkaloids according to their chemical structure belong to two main classes: the phenanthrene series, which have a pronounced narcotic effect, and the isoquinoline series, which do not have a narcotic effect, but have a myotropic antispasmodic effect (papaverine). The main opium alkaloid of the phenanthrene series is morphine.

Morphine hydrochloride has a strong analgesic effect. By reducing the excitability of pain centers, it is able to have an anti-shock effect in case of injury. Morphine causes pronounced euphoria, and with its repeated use, a painful addiction (morphinism) quickly develops. It has an inhibitory effect on conditioned reflexes, reduces the summative ability of the central nervous system, and enhances the effect of narcotic, hypnotics and local anesthetics. Morphine also reduces the excitability of the cough center. Morphine also causes stimulation of the vagus nerve center (N. vagus), which leads to bradycardia. As a result of activation of neurons of the oculomotor nerves under the influence of morphine, miosis appears. Characteristic of the action of morphine is depression of the respiratory center. Small doses cause a decrease and increase in the depth of respiratory movements; large doses provide a further slowdown and decrease in the depth of breathing with a decrease in pulmonary ventilation. Toxic doses cause the appearance of periodic breathing of the Cheyne-Stokes type and subsequent respiratory arrest.

Morphine is used as a powerful analgesic for injuries and various diseases with severe pain (malignant neoplasms, myocardial infarction, etc.), in preparation for surgery and in the postoperative period, and for insomnia associated with severe pain. Morphine is not used for labor pain relief, as it easily penetrates the fetoplacental barrier and can cause respiratory depression in the newborn. The use of morphine is currently severely limited due to its high addictive potential (high likelihood of physical dependence) and toxicity. To reduce the risk of addiction and side effects, long-acting dosage forms of morphine hydrochloride, for example, morphilong, are used.

Morfilong is a long-acting form of morphine hydrochloride. It is a 0.5% solution of morphine hydrochloride in a 30% aqueous solution of polyvinylpyrrolidone. The pharmacological action is completely identical to morphine hydrochloride. Possible side effects, precautions and contraindications are identical to morphine hydrochloride. Morfilong is used in adults and children over 7 years of age in the postoperative period and in cases of severe pain in cancer patients.

Other opium preparations include Omnopon, which is a mixture of several opium alkaloids, including papaverine. As a result, omnopon does not have a peripheral spasmogenic effect and, on the contrary, is even able to relieve spasms of smooth muscles. Contraindications and side effects are the same as for morphine.

Codeine is naturally found in small amounts in opium. The codeine content in opium is small (0.2-2%), so codeine is obtained semi-synthetically from morphine. Codeine is used in medicine in the form of a base and a phosphate. The nature of its action is similar to that of morphine, but its analgesic properties are less pronounced. It is believed that the pain-relieving properties of codeine are due to the fact that morphine is formed during the metabolism of codeine in the body. Codeine has a strong ability to reduce the excitability of the cough center. Codeine is used mainly to calm a cough. In combination with non-narcotic analgesics (analgin, paracetamol), caffeine, phenobarbital, it is used for headaches and neuralgia as part of combination drugs. It is part of Bekhterev's mixture, used as a sedative.

Codeine and codeine phosphate are included in the combined tablet preparations: “Pentalgin”, “Sedalgin”, “Solpadeine”, etc.

Ethylmorphine, like codeine, is a semi-synthetic drug. Ethylmorphine is not found in natural objects; it is produced industrially by ethylation of morphine. In medicine, ethylmorphine is used in the form of hydrochloride. By general action Ethylmorphine is similar to codeine in the body. A peculiarity of the pharmacological effect of ethylmorphine is its ability to cause hyperemia of the conjunctiva with subsequent swelling and local anesthesia. This fact allows the use of ethylmorphine in ophthalmic practice.

Ethylmorphine hydrochloride is used orally to calm cough when chronic bronchitis, pulmonary tuberculosis, etc., and also as an analgesic. Sometimes ethylmorphine hydrochloride is used in ophthalmic practice - the drug has a soothing effect on the eyes with keratitis, corneal infiltration and other eye diseases.

Morfinan derivatives. Other modern morphinan derivatives are also used as painkillers in medicine. They differ from morphine mainly in that they exert their therapeutic effect in significantly smaller doses, and, accordingly, side effects are less pronounced: respiratory depression, nausea, vomiting, etc.

Drugs in this group are synthetic, obtained by chemical modification of the morphine molecule, so they exhibit a unique effect: they are both agonists and antagonists of opiate receptors. As a result, the risk of dependence on these drugs is much lower than with morphine. Drugs in this group include: Nalorphine, Pentazocine, Lexir, Fortral, Nalbuphine, Buprenorphine, Butorphanol, Moradol.

Piperidine derivatives. The idea of creating narcotic analgesics derived from piperidol arose as a result of studying the chemical structure of the phenanthrene isoquinoline structure of morphine and other alkaloids contained in opium. Piperidine derivatives include: Promedol, Fentanyl.

Of the narcotic analgesics of synthetic origin, the most commonly used is promedol. It is inferior to morphine in its analgesic effect, but does not have a spasmogenic effect. A special feature of the drug is its effect on the pregnant uterus - it promotes the establishment of correct rhythmic contractions of the uterus and accelerates delivery. Promedol is the drug of choice for pain relief during labor, although it must be remembered that it can depress the fetal respiratory center to a certain extent, although less than morphine.

Another synthetic drug from this group, fentanyl, is one of the most powerful analgesics, but has a short duration of effect (up to 30 minutes). Its analgesic activity is approximately 200 times greater than morphine. Fentanyl is often used together with the antipsychotic drug droperidol to achieve a special type of general analgesia called neuroleptanalgesia. In this case, the patient's analgesia is accompanied by the preservation of consciousness, but the absence of feelings of fear and anxiety, and the development of indifference to surgical intervention. Used for short-term surgical interventions.

Cyclohexane derivatives are a fairly young group of narcotic analgesics, which, however, have managed to prove themselves from the best side. Drugs in this group are agonists-antagonists of opiate receptors, which reduces the risk of dependence and addiction. Drugs in this group include: Tramadol, Tramal, Tilidine, Valoron.

Tramadol's chemical structure is somewhat similar to promedol.

In medicine, tramadol is used in the form of hydrochloride. It has strong analgesic activity, but is approximately 10 times less active than morphine. The drug is well tolerated, without causing significant respiratory depression at usual doses and does not significantly affect blood circulation and the gastrointestinal tract. Used for severe acute and chronic pain: in the postoperative period, with injuries, in cancer patients, etc. It is one of the most accessible drugs of narcotic analgesics.

Derivatives of diphenylethoxyacetic acid. Narcotic analgesics that do not contain a cyclohexane or piperidine ring were discovered in the 40s of the 20th century and were widely used as cheap substitutes for morphine (in war time). Currently, drugs in this group (methadone, dextromoramide) are excluded from the State Register. The only exception is estocin, a drug that combines the properties of narcotic analgesics and m-anticholinergics.

Estocin is a synthetic narcotic analgesic. Its chemical structure is similar to a number of m-anticholinergic drugs. In terms of analgesic effect, estocin is much weaker than morphine and promedol, but it depresses breathing less and does not increase the tone of the vagus nerve; has a moderate antispasmodic and anticholinergic effect, reduces spasms of the intestines and bronchi. Estocin is used for pain associated with spasms of smooth muscles, in the preoperative and postoperative periods, for minor injuries, and for pain relief during childbirth.

2. Characteristics of modern analgesics-antipyretics

2.1 Analgesics-antipyretics registered in the Russian Federation

Based on data from the State Register of Medicines, the range of drugs of the analgesic-antipyretic group registered in the Russian Federation is presented below.

These drugs are divided into pharmacological groups and subgroups in accordance with the anatomical-therapeutic-chemical classification (ATC).

Table No. 1. ATC classification of analgesics-antipyretics

	Analgesics and antipyretics

	Acetylsalicylic acid
	Acetylsalicylic acid in combination with other drugs (excluding psycholeptics)
	Acetylsalicylic acid in combination with psycholeptics
	Pyrazolones
	Metamizole sodium
	Metamizole sodium in combination with other drugs (excluding psycholeptics)
	Metamizole sodium in combination with psycholeptics

	Paracetamol
	Paracetamol in combination with other drugs (excluding psycholeptics)
	Paracetamol in combination with psycholeptics
	Other analgesics and antipyretics

	Flupirtine

Number of trade names, manufacturers and dosage forms of each drug. are presented in Appendix No. 1.

According to the data received, the following are registered on the territory of the Russian Federation:

5 INNs of drugs from the group of analgesics-antipyretics and 40 different combinations of them;

100 trade names of all analgesics and antipyretics;

179 drugs, taking into account all forms of release. Drugs in this group are presented in the following dosage forms: tablets, effervescent tablets, extended-release tablets, capsules, syrups, granules for the preparation of solution for oral administration, solutions for injections, rectal suppositories.

Table No. 2. Structure of the range of analgesics and antipyretics registered in the Russian Federation.

Group of analgesics-antipyretics	International nonproprietary drug names (INN)	Number of trade names of the drug. abs.
		Domestic	Foreign
Salicylic acid and its derivatives	Acetylsalicylic acid
	Acetylsalicylic acid in combination with other drugs
Pyrazolones	Metamizole sodium
	Metamizole sodium in combination with other drugs
	Paracetamol
	Paracetamol in combination with other drugs
Other analgesics-antipyretics
	Flupirtine
Total abs. (%)

2.1 Analysis of the range of analgesics and antipyretics in pharmacies

Table 2. Assortment list of analgesics-antipyretics in pharmacies

		Tradename	Manufacturer	Dosage form
	Acetylsalicylic acid			pills
		Aspirin 1000	Bayer Consumer Care AG Switzerland	effervescent tablets
		Aspirin cardio	Bayer Consumer Care AG Switzerland	enteric-coated tablets
		Upsarin Upsa		effervescent tablets
		Acetylsalicylic acid	Dalkhimpharm OAO Russia	pills
				pills
				pills
	Metamizole sodium	Baralgin M	Aventis Pharma Ltd India	solution for intravenous and intramuscular administration
				pills
		Analgin-Ultra	Obolenskoye - pharmaceutical enterprise of ZAO Russia
		Analgin	Update of PFC ZAORossiya	pills
			Organics OAORussia	pills
			Pharmstandard-Tomskkhimpharm OJSC [Tomsk, Lenin Ave.] Russia	pills
			Biosynthesis OAORussia	pills
	Paracetamol	Children's Panadol		pills
			Glaxo Wellcome GmbH and Co.Germany	pills
			GlaxoSmithKline Consumer HealthcareUK	pills
		Perfalgan	Bristol-Myers SquibbFrance	pills
		Tsefekon D	Nizhpharm OAO Russia	pills
		Efferalgan	Bristol-Myers SquibbFrance	pills
			Bristol-Myers SquibbFrance	pills
			Bristol-Myers Squibb LLC USA	pills
			KRKA, d.d., Novo MestoSlovenia	pills
			Pharmstandard-Fitofarm-NN LLC [N.Novgorod]Russia	pills
		Paracetamol	Tatkhimpharmpreparaty JSC Russia	pills
			Synthesis OAORussia	pills
			Open Joint Stock Company "Organika"Russia	pills
			Biochemist OAORussia	pills
			Irbitsky Chemical Plant JSC Russia	pills
			Asfarma LLCRussia	pills
			Open Joint Stock Company "Moscow Production Chemical and Pharmaceutical Association named after N.A. Semashko" Russia	pills
			Pharmstandard-Tomskkhimpharm OJSC [Tomsk, Lenin Ave.] Russia	pills
				pills
		Paracetamol for children		pills
		Paracetamol-UBF	Uralbiopharm JSC Russia	pills
		AKUPAN®-BIOCODEX	Representative office of JSC BiocodexRussia	solution for infusion and intramuscular administration
	Flupirtine	Katadolon®forte	Teva Pharmaceutical Enterprises Ltd. Israel	extended-release tablets
Combination drugs
		Tradename	Manufacturer	Dosage form
		Alka-Seltzer	Bayer Consumer Care AG Switzerland	effervescent tablets
	Acetylsalicylic acid + Glycine&	Alca Prim	Representative office of the Pharmaceutical Plant "Polpharma" AORossia	effervescent tablets
	Acetylsalicylic acid+[Ascorbic acid]	Aspirin-S	Bayer Consumer Care AG Switzerland	effervescent tablets
	Acetylsalicylic acid+Caffeine+Paracetamol	Aquacitramon	Aquacitramon LLCRussia	granules for the preparation of solution for oral administration
		Askofen-P	Pharmstandard-Leksredstva JSC Russia	pills
		Cofficil-plus	Pharmstandard-Leksredstva JSC Russia	pills
		Citramon P	Irbitsky Chemical Plant JSC Russia	pills
			Pharmstandard-Tomskkhimpharm OJSC [Tomsk, Lenin Ave.] Russia	pills
			Nizhpharm OAO Russia	pills
			Medisorb ZAORussia	pills
			Pharmstandard-Leksredstva JSC Russia	pills
		Citramon-Borimed	Open Joint Stock Company "Borisov Plant" medical supplies» (JSC Borisov Plant of Medical Preparations) Republic of Belarus	pills
		Citramon-MFF		pills
		Excedrin®		film-coated tablets
	Acetylsalicylic acid+Caffeine+Paracetamol+[Ascorbic acid]	Citrapack	Pharmstandard-Ufa Vitamin Plant JSC Russia	pills
	Acetylsalicylic acid+Caffeine	Aspinat plus	Open Joint Stock Company "Valenta Pharmaceuticals" Russia	pills
	Acetylsalicylic acid+[Citric acid+Sodium bicarbonate]	Zorex Morning	Valenta Pharmaceuticals JSC Russia	effervescent tablets
	Metamizole sodium+Quinine	Analgin-quinine	Sopharma AOBulgaria	film-coated tablets
		Spasmalgon	Sopharma AOBulgaria	solution for intramuscular administration
	Metamizole sodium + Pitophenone + Fenpiverinium bromide	Revalgin		pills
				injection
	Codeine+Caffeine+Paracetamol+Propyphenazone+Phenobarbital	Pentalgin Plus	Pharmstandard-Leksredstva JSC Russia	pills
		Pentalgin	Pharmstandard-Leksredstva JSC Russia	film-coated tablets
	Codeine+Caffeine+Metamizole sodium+Naproxen+Phenobarbital	Pentalgin-N	Pharmstandard-Leksredstva JSC Russia	pills
		Piralgin	Belmedpreparaty RUPRepublic of Belarus	pills
			Sopharma AOBulgaria	pills
		Quintalgin	Interchem OJSC joint Ukrainian-Belgian chemical enterpriseUkraine	pills
		Santoperalgin	Khimpharm JSC Kazakhstan	pills
		Sedalgin-Neo		pills
		Tetralgin	Closed Joint Stock Company "Pharmaceutical Production Company PharmVILAR" Russia	pills
	Metamizole sodium + Triacetonamine-4-toluenesulfonate	Tempalgin	Sopharma AOBulgaria	film-coated tablets
		Tempanginol	Balkanfarma - Dupnitsa ADBulgaria	film-coated tablets
	Bendazole+Metamizole sodium+Papaverine+Phenobarbital		Uralbiopharm JSC Russia	pills
			Pharmstandard-Tomskkhimpharm OJSC [Tomsk, Lenin Ave.] Russia	pills
			Moscow endocrine plant FGUPRossiya	pills
	Ibuprofen+Codeine+Caffeine+Metamizole sodium+Phenobarbital	Pentabufen	Moscow pharmaceutical factory ZAORussia	pills
	Paracetamol+Chlorphenamine+[Ascorbic acid]	Antigrippin	Natur Product Europe B.V.Netherlands	[honey-lemon]
				effervescent tablets
				effervescent tablets [for children]
				effervescent tablets [grapefruit]
		Antiflu Kids	Sagmel Inc.USA	powder for solution for oral administration
	Paracetamol+[Ascorbic acid]	Grippostad		powder for solution for oral administration
		Paracetamol-S-Hemofarm	Hemofarm A.D.Serbia	effervescent tablets
		Efferalgan with vitamin C	Bristol-Myers SquibbFrance	effervescent tablets
	Caffeine+Paracetamol+Chlorphenamine+[Ascorbic acid]	Grippostad S	STADA Arzneimittel AGGermany
	Codeine+Caffeine+Paracetamol+Propyphenazone	Kaffetin		pills
			Bayer Consumer Care AG Switzerland	pills
	Dextromethorphan+Paracetamol+Pseudoephedrine+[Ascorbic acid]	Kaffetin Cold	Alkaloid AORRepublic of Macedonia	film-coated tablets
	Codeine+Paracetamol	Codelmixt	Rusan Pharma Ltd. India	pills
	Caffeine+Paracetamol+Terpin hydrate+Phenylephrine+[Ascorbic acid]	Coldrex		pills
		Flucoldex forte	Sketch Pharma Pvt.LtdIndia	film-coated tablets
	Paracetamol+Phenylephrine+[Ascorbic acid]	Coldrex® MaxGripp	GlaxoSmithKline Consumer HealthcareUK
		Coldrex HotRem	GlaxoSmithKline Consumer HealthcareUK	powder for solution for oral administration [lemon-honey]
				powder for oral solution [lemon]
		Flucoldex®-S	Sketch Pharma Pvt. Ltd.India	powder for solution for oral administration
	Drotaverine+Codeine+Paracetamol	No-shpalgin	Hinoin Pharmaceutical and Chemical Products Plant A.O. Hungary	pills
				pills
	Caffeine+Paracetamol+Phenylephrine+Chlorphenamine		Unique Pharmaceutical Laboratories (A Division of J.B. Chemicals and Pharmaceuticals Ltd.) India	pills
		Rinicold	Shreya Life Sciences Pvt.Ltd India	pills
	Caffeine+Paracetamol+Phenylephrine+Pheniramine	Rinzasip	Unique Pharmaceutical Laboratories (A Division of J.B. Chemicals and Pharmaceuticals Ltd.) India	powder for oral solution [lemon]
	Codeine+Caffeine+Paracetamol	Solpadeine	GlaxoSmithKline Consumer HealthcareUK	pills

			GlaxoSmithKline Consumer HealthcareIreland	soluble tablets
	Caffeine+Paracetamol	Solpadeine Fast	GlaxoSmithKline Consumer HealthcareUK	soluble tablets
	Paracetamol+Phenylephrine+Pheniramine+[Ascorbic acid]	Stopgripan forte	ratiopharm India Pvt. LimitedIndia	powder for oral solution [lemon]
		TheraFlu® for colds and flu	Novartis Consumer Health CA Switzerland	powder for oral solution [lemon]
	Paracetamol+Phenylephrine+Pheniramine	TeraFlu®	Novartis Consumer Health CA Switzerland	powder for solution for oral administration [wild berries]
	Paracetamol+Phenylephrine+Chlorphenamine	TheraFlu® ExtraTab	Novartis Consumer Health CA Switzerland	film-coated tablets
			Bristol-Myers SquibbFrance	powder for oral solution [lemon]
				powder for oral solution [lemon with sugar]
		Fervex for children	Bristol-Myers Squibb LLC USA	powder for solution for oral administration
	Drotaverine+Paracetamol	Unispaz N	Unique Pharmaceutical Laboratories (A Division of J.B. Chemicals and Pharmaceuticals Ltd.) India	pills
	Paracetamol+Chlorphenamine	Flucoldex	Sketch Pharma Pvt.LtdIndia	syrup [for children]
	Caffeine+Paracetamol+Chlorphenamine	Flucoldex-N	Sketch Pharma Pvt. Ltd.India	pills

Conclusion: the leading drugs from the group of analgesics-antipyretics in pharmacies are: paracetamol, as well as combination drugs of paracetamol, metamizole sodium and acetylsalicylic acid. A large proportion of analgesics and antipyretics are imported drugs. 78% of drugs from the analgesic-antipyretic group in pharmacies are “analogues” of original drugs.

Conclusion

1. Analgesics are drugs that have the specific ability to weaken or eliminate the feeling of pain, i.e. drugs whose dominant effect is analgesia.

Analgesics are divided into two large groups: narcotic and non-narcotic.

Narcotic analgesics are characterized by strong analgesic activity, which makes them possible to use as highly effective painkillers in various fields of medicine, especially for injuries and diseases accompanied by severe pain.

Non-narcotic analgesics are a group of drugs most often used to relieve pain.

Unlike narcotic analgesics, when using this group of analgesics, addiction and drug dependence do not occur; they do not affect the basic functions of the central nervous system during wakefulness (do not cause drowsiness, euphoria, lethargy, do not reduce reactions to external stimuli, etc.) .

Therefore, non-narcotic analgesics are widely used for headaches, toothaches, neuralgia, myalgia, myositis and many other diseases accompanied by pain.

The state register of medicines includes: 5 INN drugs from the group of analgesics-antipyretics and 40 different combinations of them; 100 trade names of analgesics and antipyretics. These data show that a large number of drugs of this group are registered in the Russian Federation.

This is due to the widespread use of these drugs in medical practice for various diseases. Leading drugs: paracetamol, as well as combination drugs of paracetamol, metamizole sodium and acetylsalicylic acid. A significant proportion of analgesics and antipyretics in pharmacies are made up of imported drugs. Most drugs are generics.

Bibliography

1. the federal law Russian Federation dated April 12, 2010 No. 61 “On the circulation of medicines.”

2. Federal Law No. 323-FZ “On the Protection of Citizens’ Health” [Electronic resource].

3. Order of the Ministry of Health of the Russian Federation dated October 21, 1997 No. 309 “On approval of instructions on the sanitary regime of pharmacy organizations.” [Electronic resource].

4. State Pharmacopoeia RF. - GF XIII, 2015, FMEB,

5. Nasonov Yu.A. Non-steroidal anti-inflammatory drugs / - M.: Medicine, 2014.

6. Kharkevich D.A.. Pharmacology. M.: Geotar-Med, 2010.

7. Mashkovsky M.D. Medicines. - 16 - ed. Reworked, corrected And additionally - M.: New Wave Publisher Umerenkov. 2014.- 1216 p.

8. Directory Vidal Medicines in Russia. Directory. M.: Vidal Rus, 2015. 1480 p.

9. Anti-inflammatory effect. NSAIDs Electronic resource.

10. Analgesic effect Electronic resource.

11. Antipyretic effect. [Electronic resource].

13.Paracetamol as an antipyretic [Electronic resource]

Applications

Appendix No. 1

A range of analgesics and antipyretics registered in the Russian Federation.

	Tradename	Manufacturer	Dosage form
Acetylsalicylic acid		Bayer Consumer Care AG Switzerland	pills
	Aspirin 1000	Bayer Consumer Care AG Switzerland	effervescent tablets
	Aspirin cardio	Bayer Consumer Care AG Switzerland	enteric-coated tablets
	Acecardole	Synthesis OAORussia	enteric-coated tablets
	CardiASK	Kanonpharma production ZAORussia	enteric film-coated tablets
	Upsarin Upsa	Bristol-Myers Squibb LLC USA	effervescent tablets
	Aspinat 300	Valenta Pharmaceuticals JSC Russia	enteric-coated tablets
	Acetylsalicylic acid "York"	International Trade Association of America Inc.USA	pills

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Description of pain as a physiological mechanism. Determination of the degree of involvement of various parts of the nervous system in the formation of pain. The use of opiates, non-steroidal anti-inflammatory drugs, simple and combined analgesics.

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

Painful sensations arise from destructive harmful irritations and are danger signals, and in the case of traumatic shock they can cause death. Elimination or reduction of pain helps to improve the patient’s physical and mental condition and improve his quality of 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.

Painful sensations are perceived by special receptors - nociceptors. There are endogenous substances that are formed when tissue is damaged 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 and mucous membranes).

Deep pain has varying duration and the ability to spread to other areas (occurs in case of irritation of nociceptors located in the muscles, joints, and thighs).

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

The antinociceptive system disrupts the perception of pain, the conduction of pain impulses and the formation of reactions. This system includes endorphins, which are produced in the pituitary gland, hypothalamus and enter the blood. their secretion increases under stress, during pregnancy, during childbirth, under the influence of dinitrogen oxide, fluorotane, 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 effects), pain sensations are suppressed with the help of analgesics.

Analgesics (from Greek. Algos- pain hap- negation) - this medications, which, with a resorptive effect, 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 (piritra-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 indoloctic 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 mefenamate, piroxicam, meloxicam (movalis) Combined drugs: Reopirin, sedalgin, tempalgin, baralgin, citramon, Citropak, tsnklopak, asconar, para vit

Narcotic analgesics

Narcotic analgesics- these are drugs that, during 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 caused by 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 the drug); inhibition of the cough reflex (this effect is used for coughs that are accompanied by pain or bleeding - with wounds, rib fractures, abscesses, etc.); sedative effect; hypnotic effect; euphoria - the disappearance of unpleasant emotions, feelings of fear and tension; nausea and vomiting as a consequence 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 reflexes, etc.); miosis (constriction of the pupils) - due to increased tone of the nucleus of the oculomotor center;

- Peripheral: constipation effect associated with the occurrence of spastic contractions of the sphincters, limitation of peristalsis; bradycardia and arterial hypotension caused by increased tone of the vagus nerve nucleus; increased tone of smooth muscles of the bladder and sphincter urethra(renal problems may occur colic and urinary retention, which are undesirable in the postoperative period); hypothermia (so 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 pill poppy, contains more 20 alkaloids). Morphine is the main drug in the group of narcotic analgesics. It is characterized by a strong analgesic effect, pronounced euphoria, and with repeated administrations, drug dependence (morphinism) quickly occurs. Characteristic is 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. Consumption in toxic doses leads to respiratory arrest.

Morphine is rapidly absorbed both when taken orally and when administered subcutaneously. The effect occurs 10-15 minutes after subcutaneous administration and 20-30 minutes after oral administration and lasts 3-5 hours. Penetrates well through the GBD and the placenta. Metabolism occurs in the liver and is excreted in the urine.

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

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

Ethylmorphine hydrochloride(dionine) - superior to codeine in its analgesic and antitussive effects. When administered into the conjunctival sac, it improves blood and lymph circulation, normalizes metabolic processes, helps eliminate pain and resolve exudates and infiltrates in diseases of the eye tissue.

Used for cough and pain 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 the analgesic effect of morphine and provides an antispasmodic effect (contains papaverine).

It is used in such cases, like morphine, but omnopona is more effective for spastic pain. Injected subcutaneously.

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

Indications for use: as an analgesic for injuries, in the pre- and postoperative period. Prescribed to patients with gastric and duodenal ulcers, angina pectoris, myocardial infarction, intestinal, hepatic and renal colic and other spastic conditions. In obstetrics it is used to relieve pain during childbirth. Prescribed subcutaneously, intramuscularly and orally.

Fentanyl- a synthetic drug that is 100-400 times superior in analgesic effect to morphine. After intravenous administration maximum effect 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 skeletal muscle tone. Bradycardia often occurs.

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

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

Butorphanol(moradol) by pharmacological properties close to pentazocine. Prescribed for severe pain, in the postoperative period, for cancer patients, in case of renal colic, injuries. Administer 2-4 mg of a 0.2% solution intramuscularly or 1-2 mg of a 0.2% solution intravenously.

Tramadol- a strong analgesic of central action. There are two mechanisms of action: it binds to opioid receptors, due to which the sensation of pain is weakened, and also suppresses the reuptake of norepinephrine, as a result of which the transmission of pain impulses in the spinal cord is inhibited. Tramadol does not suppress breathing and does not cause dysfunction of the cardiovascular system. The action comes quickly and lasts several hours.

Indications for use: severe pain of various origins (due to injury), 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 (into 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 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 signs are pathological breathing 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;

Taking 20-30 g of activated carbon

Salt rinsing;

Intravenous and intramuscular administration of the antagonist naloxone (Narcan). The drug acts quickly (1 minute), but does not last long (2-4 hours). For long-term action, nalmefene should be administered intravenously (valid for 10 hours);

There may be a need for artificial respiration;

Warm 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 syndrome. Tolerance appears after 2-3 weeks (sometimes earlier) when the drug is administered in therapeutic doses.

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

Chronic use of opioids leads to chronic poisoning, which reduces mental and physical performance, exhaustion, thirst, constipation, hair loss, etc.

Treatment for opioid addiction is complex. These are detoxification methods, the introduction of an opioid antagonist - naltrexone, symptomatic drugs and the implementation of measures to prevent the addict from contacting his usual environment. However, radical cure is achieved in a small percentage of cases. Most patients experience relapses, so preventive measures are important.

Pharmacosafety:

- 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 the same syringe with chlorpromazine;

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

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

- Pentazocine and barbiturates cannot be administered in the same syringe;

- Opium drugs inhibit intestinal motility and may delay the absorption of other drugs prescribed orally;

- Codeine in complex preparations practically does not cause anauria and addiction.

Narcotic analgesics

Drug name		Release form		Mode of application	Higher doses and storage conditions
Morphine hydrochloride (Mogrpi pi hydrockloridum)		Powder 1% solution in ampoules and syringe tubes of 1 ml (10 mg/ml)		Orally 0.01-0.02 g after meals subcutaneously, intramuscularly 1 ml of 1% solution, intravenously (slowly)	VRD - 0.02 g, VDD - 0.05 g List A In a place protected from light
Codeine (Codeinum)		Powder, tablets 0.015 g		Orally 0.01-0.02 g 3-4 times a day before meals	VRD-0.05 g, VDD-0.2 List B In a place protected from light
Codeine phosphate (Codeini phosphas)		soluble		Orally 0.01-0.02 g 2-3 times in powders, mixtures	VRD-0.1, VDTs-0, Zg List B In a place protected from light
Ethylmorphine hydrochloride (Aethylmor- phini hydrochloro-		Powder, tablets 0.01; 0.015 g		Orally 0.01-0.015 g 2-3 times a day; 1-2% solution, 1-2 drops into the conjunctival slit	VRD-0.03 g, VDD-0.1 List A In a place protected from light
Promedol (Promedolum)		Powder tablets 0.025 g 1 (10 mg/ml) and 2% solution in ampoules and syringe tubes 1 ml (20 mg/ml)		Orally 0.025 g before meals subcutaneously 1 ml of 1 or 2% solution	List A In a tightly sealed container
Fentanyl (Phentanylum)		0.005% solution in ampoules of 2 and 5 ml (0.05 mg/ml)		Intramuscular and intravenous 1-2 ml (0.00005-0.0001 g)
Antagonist of narcotic analgesics
Naloxone hydrochloride	0.04% solution in 1 ml ampoules (0.4 mg/ml)		Subcutaneously, intramuscularly, intravenously, L2 ml (0.0004-0.008 g)

Non-narcotic analgesics

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

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

The filling process involves various cellular elements (mast cells, endothelial cells, platelets, monocytes, macrophages), which secrete biologically active substances: prostaglandins, thromboxane AZ, prostacyclin - inflammatory mediators. Cyclookeinase (COX) enzymes 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 exudative and proliferative phase inflammation. The effect is achieved after a few days.

Analgesic effect observed after a few hours. The drugs primarily affect pain during 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. Reducing body temperature to 38 "C is not advisable, because low-grade fever- this is a protective reaction of the body (the activity of phagocytes and interferon production increase, etc.).

Salicylates

Acetylsalicylic acid(aspirin) is the first representative of non-narcotic analgesics. The drug has been used since 1889. It is produced in tablets and is part of such combination drugs as citramon, sedalgin, coficil, 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 antiaggregation 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 during the postoperative period, for rheumatic pain, and cancer.

Sodium salicylate as an analgesic and antipyretic drug prescribed orally after meals to patients acute rheumatism and rheumatoid endocarditis, sometimes administered intravenously.

Derivatives of pyrazolone and indoloctic acid

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

Indications for use: for pain of various origins (headache, toothache, pain due to injuries, neuralgia, radiculitis, myositis, fever, rheumatism). Prescribed orally after meals for adults, and also administered intramuscularly and intravenously.

Side effect swelling, increased blood pressure, toxic effects on hematopoiesis (blood formula changes).

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

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

Indomethacin(methindol) - has a pronounced analgesic, anti-inflammatory and antipyretic effect. Prescribed to patients with rheumatoid arthritis, osteoarthritis, gout, thrombophlebitis. It is used orally, and indomethacin ointment is rubbed in for acute and chronic polyarthritis and radiculitis.

Para-aminophenol derivatives

Paracetamol(Panadol, Efferalgan, Tylenol) - according to its 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 as part of such combination drugs as coldrex, solpadeine, dol-extra pas.

Alkanoic acid derivatives

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 digestive tract, almost completely binds to blood plasma proteins. Excreted in urine and bile in the form of 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, spondyloarthrosis 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 persons 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, helps to increase the range of movements in them.

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

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

Chemical preparations

Ketorolac(ketanov) has pronounced analgesic activity, significantly superior to the activity of other non-narcotic analgesics. Less pronounced are the antipyretic and anti-inflammatory effects. The drug blocks COX-1 and COX-2 (cyclooxygenase) and thus prevents the formation of prostaglandins. Prescribed orally for adults and children over 16 years of age for injuries, toothache, myalgia, neuralgia, radiculitis, dislocations. Administered intramuscularly for postoperative and postoperative pain. 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. Prescribe with caution to patients with bronchial asthma, liver dysfunction, and heart failure.

Mefenamic acid- inhibits the formation and eliminates inflammation from tissue depots of mediators (serotonin, histamine), suppresses the biosynthesis of prostaglandins, etc. The drug increases cell resistance to damaging effects, effectively eliminates acute and chronic toothache and pain in muscles and joints; exhibits antipyretic effect. Unlike other anti-inflammatory drugs, it has almost no ulcerogenic effect.

Sodium mefenaminate- similar in action to mefenamic acid. At local application helps accelerate the healing of wounds and ulcers.

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

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 has a long-lasting effect. It is excreted mainly by the kidneys.

Indications for use: osteoarthritis, spondyloarthrosis, rheumatoid arthritis, radiculitis, gout.

Meloxicam(movalis) - selectively blocks COX-2, an enzyme that is formed at the site 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 treatment of patients with rheumatoid arthritis, osteoarthritis, arthrosis with severe pain.

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

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

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

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 long-term use, especially in high doses);

Hallucinations (indomethacin). Prescribe with caution to patients with mental disorders, epilepsy and parkinsonism.

Pharmacosafety:

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

- To prevent the damaging effects of drugs on the mucous membranes, the patient should be taught to take medications correctly (with food, milk or a full glass of water) and to recognize the signs of a 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 if symptoms of agranulocytosis appear (feeling cold, fever, sore throat, malaise)

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

- Remind the patient that if drowsiness occurs after taking indomethacin, do not drive a car or operate dangerous equipment;

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

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

CLINICAL PHARMACOLOGY OF THE MOST COMMONLY USED ANTIPECHYMIC DRUGS

When choosing medications for children, it is especially important to focus on drugs with the lowest risk of severe side effects. This is especially relevant due to the fact that most children with acute viral diseases are at home and parents often prescribe antipyretics on their own before the doctor arrives. At the same time, there is a significant difference in what medications parents should use before the pediatrician arrives and which ones should be prescribed under the supervision of a doctor.

Currently, it is customary to distinguish two groups among analgesics-antipyretics:

non-steroidal anti-inflammatory drugs (NSAIDs - acetylsalicylic acid, ibuprofen, etc.);
paracetamol (Fig. 1).

At doses recommended for over-the-counter use, NSAIDs and paracetamol have similar antipyretic and analgesic effects, although paracetamol does not have a clinically significant anti-inflammatory effect. The key difference between paracetamol and NSAIDs is safety, which is directly related to their mechanism of action.

Figure 1. Classification of non-narcotic analgesics and antipyretics allowed for sale without a prescription in the Russian Federation.

It is generally accepted that the mechanism of action of all antipyretics is to block the synthesis of prostaglandins along the cyclooxygenase pathway in the hypothalamus. At the same time, the anti-inflammatory effect of NSAIDs is associated with blocking the synthesis of prostaglandins not only in the hypothalamus, but also in other organs and systems. Along with the anti-inflammatory effect, NSAIDs block the synthesis of protective prostaglandins, which can lead to severe complications: gastrointestinal bleeding, asthma, acute renal failure, etc. The antipyretic and analgesic effect of paracetamol, unlike NSAIDs, is central in nature (pain and thermoregulation centers in the central nervous system) and does not suppress the synthesis of protective prostaglandins in other organs and systems, which determines its greater safety profile compared to NSAIDs.

A key safety issue for analgesic-antipyretic drugs is the high risk of gastrointestinal bleeding due to NSAID use. It has been established that more than 50% of all acute gastrointestinal bleeding is associated with the use of NSAIDs, and 84% of them are caused by over-the-counter NSAIDs. As is known, mortality from gastrointestinal bleeding reaches 10%.

Aspirin asthma is another serious complication use of NSAIDs, especially against the backdrop of a steady increase in the incidence of childhood bronchial asthma (from 10% to 15-20%).

Along with gastrointestinal bleeding and bronchial obstruction, NSAIDs can cause:

severe changes in bone marrow hematopoiesis, including fatal agranulocytosis (metamizole);
acute renal failure(indomethacin, ibuprofen);
thrombocytopathy with hemorrhagic syndrome (ASC);
anaphylactic shock (metamizole);
Reye's syndrome (RS);
hepatitis (aspirin);
and many other complications.

Paracetamol is as effective as NSAIDs such as acetylsalicylic acid and ibuprofen, but it does not cause many of the severe side effects common to all NSAIDs.