JOURNAL "PRACTICE OF PEDIATRICS"
O.V. Zaitseva, Professor, Head of the Department of Pediatrics, State Educational Institution of Higher Professional Education "Moscow State University of Medicine and Dentistry" of Roszdrav, Dr. med. Sciences
Non-opioid analgesics (analgesics-antipyretics) are among the most widely used drugs in pediatric practice. They are distinguished by a unique combination of antipyretic, anti-inflammatory, analgesic and antithrombotic mechanisms of action, which makes it possible to use these drugs to alleviate the symptoms of many diseases.
Despite the high effectiveness of antipyretic analgesics, their use in children is not always safe. The use of acetylsalicylic acid (Aspirin) for viral infections in children may be accompanied by Reye's syndrome. In addition, acetylsalicylic acid increases the risk of developing inflammatory changes in the gastrointestinal tract, disrupts blood clotting, increases vascular fragility, and in newborns it can displace bilirubin from its association with albumin and thereby contribute to the development of bilirubin encephalopathy.
Amidopyrine was excluded from the drug nomenclature due to its high toxicity. metamizole (Analgin) can inhibit hematopoiesis up to the development of fatal agranulocytosis, which contributed to a sharp restriction of its use in many countries of the world. However, in urgent situations (hyperthermic syndrome, acute pain in the postoperative period), not amenable to other therapy, parenteral use of Analgin is acceptable.
Currently, only acetaminophen and ibuprofen fully meet the criteria for high efficacy and safety and are recommended by WHO and national programs as antipyretic drugs for pediatric use.
DRUGS OF CHOICE
Acetaminophen and ibuprofen can be given to children as young as 3 months of age. Single doses of acetaminophen - 10-15 mg / kg, ibuprofen - 5-10 mg / kg. Re-use of antipyretics is possible not earlier than after 4-5 hours, but not more than 4 times a day.
Acetaminophen (Paracetamol) has antipyretic, analgesic and slight anti-inflammatory effects, as it blocks COX predominantly in the central nervous system and does not have a peripheral effect. Qualitative changes in the metabolism of Paracetamol depending on the age of the child, which are determined by the maturity of the cytochrome P450 system, were noted. In violation of the functions of the liver and kidneys, there may be a delay in the excretion of this drug and its metabolites. A daily dose of 60 mg / kg in children is safe, but with its increase, a hepatotoxic effect of the drug may be observed. If a child has a deficiency of glucose-6-phosphate dehydrogenase and glutathione reductase, the administration of Paracetamol can cause hemolysis of red blood cells.
Ibuprofen (Nurofen for Children, RECKITT BENCKISER HEATHCARE) has a pronounced antipyretic, analgesic and anti-inflammatory effect. Most studies show that ibuprofen is as effective for fever as is acetaminophen. Other studies have found that the antipyretic effect of ibuprofen at a dose of 7.5 mg/kg is higher than that of acetaminophen at a dose of 10 mg/kg. This was manifested by a large decrease in temperature after 4 hours, which was also observed in a larger number of children. The same data were obtained in a double-blind, parallel group study with repeated administration of ibuprofen at doses of 7 and 10 mg/kg and acetaminophen at a dose of 10 mg/kg in children from 5 months to 13 years.
The pain syndrome worsens the child's well-being, slows down reparative processes and, as a result, recovery. Clinical studies indicate that ibuprofen and, to a lesser extent, acetaminophen are the drugs of choice in the treatment of acute pain of moderate intensity in children.
Ibuprofen (already at a dose of 5 mg / kg) has a dual analgesic effect - peripheral and central, and it is more pronounced than that of aceaminophen. This allows the effective use of ibuprofen for mild to moderate sore throat, acute otitis media, toothache, teething pain, and also for the relief of post-vaccination reactions.
CLINICAL STUDY
In order to study the clinical efficacy of ibuprofen in children with infectious and inflammatory diseases accompanied by fever and / or pain syndrome, we conducted an open, uncontrolled study in which Nurofen for children was used in 67 children with acute respiratory viral infections and in 10 children with tonsillitis aged from 3 months to 15 years. In 20 patients, ARVI proceeded against the background of mild to moderate bronchial asthma without indications of aspirin intolerance, in 17 patients with broncho-obstructive syndrome, in 12 with manifestations of acute otitis media, in 14 patients it was accompanied by severe headache and/or muscle aches. In 53 children, the disease was accompanied by high fever; Nurofen for children was prescribed to 24 patients with subfebrile temperature only for analgesic purposes. Nurofen suspension for children was used in a standard single dosage of 5 to 10 mg/kg 3-4 times a day. The duration of taking Nurofen for children ranged from 1 to 3 days.
The study of the clinical condition of patients included an assessment of the antipyretic and analgesic effect of Nurofen for children, registration of adverse events.
In 48 children, a good antipyretic effect was obtained after taking the first dose of the drug. Most of the young patients Nurofen for children was prescribed no more than 2 days. In 4 patients, the antipyretic effect was minimal and short-lived. 2 of them were prescribed diclofenac, 2 others used lytic mixture parenterally.
The decrease in pain intensity after the initial dose of Nurofen for children was observed after 30-60 minutes, the maximum effect was observed after 1.5-2 hours. The duration of the analgesic effect ranged from 4 to 8 hours. After the first dose of the drug, an excellent or good analgesic effect was achieved in more than half of the children, satisfactory - in 28%, and only 16.6% of patients had no analgesic effect. A day after the start of therapy, 75% of patients noted a good and excellent analgesic effect, a satisfactory relief of pain was recorded in 25% of cases. On the 3rd day of observation, the children practically did not complain of pain.
It should be noted that Nurofen for children has a pleasant taste and is well tolerated by children of all ages. We did not observe any side effects from the digestive organs, the development of allergic reactions, or the intensification or provocation of bronchospasm.
Today, ibuprofen and acetaminophen are the drugs of choice in children with moderate fever and pain, and ibuprofen is widely used as an anti-inflammatory agent. With timely and adequate appointment, such therapy brings relief to a sick child, improves his well-being and contributes to a quick recovery.
The list of used literature is in the editorial office.
The action of antipyretic drugs (antipyretics) is aimed at reducing elevated body temperature in various pathological conditions.
An increase in temperature accompanies many infectious diseases and is aimed at destroying the pathogen. The harmful effect of heat on the body begins to manifest itself when the limit is exceeded above 40°C. Therefore, it is more correct not to rush to take an antipyretic if the temperature is less than 38-38.5 gr.C.
As a rule, a decrease in high temperature is accompanied by sweating, and an increase is accompanied by chills. The easier the decline occurs, the longer the "hold" period, and the less chills when the temperature rises, the more valuable the antipyretic drug is considered to be for use.
Preparations of this group are available in tablets, powders, suppositories, syrups. This allows you to choose the appropriate dosage form depending on the age and tolerability of the drug.
Classification and properties of antipyretics
Analgesics-antipyretics
- Analgin. It has pronounced antipyretic and analgesic (pain-relieving) properties. But to reduce fever, it is taken in cases where the temperature exceeds 39°C, and other means do not help. It is banned in many countries due to a side effect that affects the state of the blood (agranulocytosis).
Preparations containing analgin - analgin ultra, baralgin, analgin-quinine, sedalgin. - Paracetamol. Acts directly on the centers of thermoregulation and pain. Taking paracetamol is accompanied by the lowest risk of any side effects, but if the dosage is exceeded or taken for a long time, a negative effect on the liver may occur. In combination with caffeine, the antipyretic effect is enhanced.
Included in the preparations of kalpol, ibuklin, panadol, cefecon, almost all combined anti-cold powders and tablets. - Propyphenazone. The safest among the representatives of this group. When using it, there were no cases of agranulocytosis.
A component of pentalgin, saridon, and many other cold remedies.
Non-steroidal anti-inflammatory drugs
The mechanism of action is based on the inhibition of the cyclooxygenase enzyme, which reduces the production of prostaglandins, bradykinins and other inflammatory mediators, and reduces the sensitivity of the thermoregulatory center to the pyrogenic effects of these substances. In addition, heat transfer is enhanced due to the expansion of peripheral vessels and increased sweating.
Preparations of this group should be used with caution in diseases of the stomach, bronchial asthma (they can provoke an attack).
- Acetylsalicylic acid. In combination with paracetamol, they enhance the action of each other, which allows you to reduce the dosage and reduce side effects, quickly reduce the temperature, body aches.
Preparations based on acetylsalicylic acid: citramon, coficil, askofen, aspirin. - Ibuprofen. Perhaps the most optimal in terms of efficiency / safety. Widely used in pediatrics in the form of syrups.
Included in the preparations ibufen, nurofen, ibuklin, fastik, moment, next, etc. - Nimesulide. Convenient in cases where the inflammatory disease is accompanied by pain.
Produced in the form of preparations nise, nimesil. - meloxicam. It is often prescribed for joint inflammatory diseases with a rise in temperature.
Drugs - Movasin, Amelotex.
homeopathic remedies
- Viburkol. Suppositories containing extracts from medicinal herbs in homeopathic doses. Can be used in children from the first days of life. Side effects are extremely rare in the form of an allergy.
- Flu hel. Approved for use in children from the first days of life. Side effects and contraindications were not found.
Medical terms: oncological diseases, neuroleptanalgesia, gout, sciatica, myositis, rheumatism, angina pectoris, myocardial infarction, hepatic and renal colic, keratitis, iritis, cataract, rheumatoid arthritis, osteoarthritis, thrombophlebitis.
Pain sensations occur with destructive harmful stimuli and are danger signals, and in the case of traumatic shock, they can be the cause of death. Elimination or reduction of the severity of pain improves the physical and mental condition of the patient, improves the quality of his life.
There is no pain center in the human body, but there is a system that perceives, conducts pain impulses and forms a reaction to pain - nociceptive (from lat. Therefore- damaging), that is, painful.
Pain sensations are perceived by special receptors - nociceptors. There are endogenous substances that are formed during tissue damage and irritate nociceptors. These include bradykinin, histamine, serotonin, prostaglandins, and substance P (a polypeptide consisting of 11 amino acids).
Types of pain
Superficial epicritical pain, short-term and acute (occurs in case of irritation of nociceptors of the skin, mucous membranes).
Deep pain, has a different duration and ability to spread to other areas (occurs in case of irritation of nociceptors located in muscles, joints, hams).
Visceral pain occurs during irritation of the pain receptors of the internal organs - the peritoneum, pleura, vascular endothelium, meninges.
The antinociceptive system disrupts the perception of pain, the conduction of a pain impulse and the formation of reactions. The composition of this system includes endorphins, which are produced in the pituitary gland, hypothalamus and enter the bloodstream. their excretion increases under stress, during pregnancy, during childbirth, under the influence of dianitrogen oxide, halothane, ethanol, and depends on the state of the higher nervous system (positive emotions).
In case of insufficiency of the nociceptive system (with excessive pronounced and prolonged damaging effect), pain is suppressed with the help of analgesics.
Analgesics (from the Greek. Algos- pain hap- denial) - these are drugs that, with a resorptive action, selectively suppress pain sensitivity. Other forms of sensitivity, as well as consciousness, are preserved.
Classification of analgesics
1. Narcotic analgesics (opioids): opium alkaloids- morphine, codeine, omnopon
Synthetic morphine substitutes: ethylmorphine hydrochloride, promedol, fentanyl, sufentanil, methadone, dipidolor (pyritra-med), estocin, pentazocine, tramadol (tramal), butorphanol (moradol), buprenorphine, tilidine (valorone)
2. Non-narcotic analgesics:
Salicylates- acetylsalicylic acid, acelysin (aspirin), sodium salicylate
Derivatives of pyrazolone and indolic acid: indomethacin (methinodol), butadione, analgin (metamizole-sodium) para-aminophenol derivatives: paracetamol (panadol, lecadol) derivatives of alkanoic acids: ibuprofen, diclofenac sodium (Voltaren, Ortofen), naproxen (Naproxia) - mefenamic acid, sodium mefenaminate, piroxicam, meloxicam (Movalis) Combined drugs: Reopirin, sedalgin, tempalgin, baralgin, citramon, Citropack, tsnklopak, asconar, para vit
Narcotic analgesics
Narcotic analgesics- these are drugs that, with a resorptive action, selectively suppress pain sensitivity and cause euphoria, addiction, and mental and physical dependence (drug addiction).
The pharmacological effects of narcotic analgesics and their antagonists are due to interaction with opioid receptors that are present in the central nervous system and peripheral tissues, as a result of which the process of interneuronal transmission of pain impulses is inhibited.
According to the strength of the analgesic effect, narcotic analgesics can be arranged in the following order: fentanyl, sufentanil, buprenorphine, methadone, morphine, omnopon, promedol, pentazocine, codeine, tramadol.
Pharmacological effects:
- Central: analgesia; respiratory depression (the degree depends on the dose of oshoidiv); inhibition of the cough reflex (this effect is used for coughing, which is accompanied by pain or bleeding - with injuries, rib fractures, abscesses, etc.); sedative effect; hypnotic effect; euphoria - the disappearance of unpleasant emotions, a feeling of fear and tension; nausea and vomiting as a result of activation of dopamine receptors in the trigger zone (occur in 20-40% of patients in response to the first injection of opioids); increased spinal reflexes (knee, etc.); miosis (narrowing of the pupils) - due to an increase in the tone of the nucleus of the oculomotor center;
- Peripheral: obstipation effect associated with the occurrence of spastic contractions of sphincters, restriction of peristalsis; bradycardia and arterial hypotension due to an increase in the tone of the nucleus of the vagus nerve; an increase in the tone of the smooth muscles of the bladder and urethral sphincter (renal colic and urinary retention, which are undesirable in the postoperative period); hypothermia (this is how the patient should be warmed and often change the position of the body in bed).
Morphine hydrochloride- the main alkaloid of opium, which was isolated in 1806 by V.A. Serturner and named after the Greek god of sleep, Morpheus (opium is the dried juice from the heads of the sleeping poppy, contains more 20 alkaloids). Morphine is the main drug of the group of narcotic analgesics. It is characterized by a strong analgesic effect, pronounced euphoria, and with repeated injections, drug dependence (morphinism) quickly occurs. Characteristic is the depression of the respiratory center. Taking the drug in low doses causes a slowdown and increase in the depth of respiratory movements, in high doses it contributes to a further slowdown and decrease in the depth of breathing. Use in toxic doses leads to respiratory arrest.
Morphine is rapidly absorbed both when administered orally and subcutaneously. The action occurs 10-15 minutes after subcutaneous administration and 20-30 minutes after ingestion and lasts 3-5 hours. It penetrates well through GBB and the placenta. Metabolism occurs in the liver and is excreted in the urine.
Indications for use: as an anesthetic for myocardial infarction, in the pre- and postoperative period, for injuries, oncological diseases. Assign subcutaneously, as well as inside in powders or drops. Children under 2 years of age are not prescribed.
Codeine is used as an antitussive or dry cough because it suppresses the cough center to a lesser extent.
Ethylmorphine hydrochloride(dionin) - surpasses codeine in the strength of analgesic and antitussive action. When introduced into the conjunctival sac, it improves blood and lymph circulation, normalizes metabolic processes, helps to eliminate pain and resolve exudates and infiltrates in case of eye tissue disease.
It is used for cough and pain syndrome caused by bronchitis, bronchopneumonia, pleurisy, as well as keratitis, iritis, iridocyclitis, traumatic cataract.
Omnopon contains a mixture of opium alkaloids, including 48-50% morphine and 32-35% other alkaloids. The drug is inferior in analgesic effect to morphine and gives an antispasmodic effect (contains papaverine).
It is used in such cases as morphine, but omnopon is more effective for spastic pain. Enter subcutaneously.
Promedol- Synthetic analgesic. In terms of analgesic effect, it is 2-4 times inferior to morphine. The duration of action is 3-4 hours. Less likely than morphine, it causes nausea and vomiting, and to a lesser extent it depresses the respiratory center. Reduces the tone of smooth muscles of the urinary tract and bronchi, increases the tone of the intestines and biliary tract. Enhances rhythmic contractions of the myometrium.
Indications for use: as an anesthetic for injuries, in the pre- and postoperative period. Assign to patients with gastric ulcer and duodenal ulcer, angina pectoris, myocardial infarction, intestinal, hepatic and renal colic and other spastic conditions. In obstetrics, it is used to anesthetize childbirth. Assign subcutaneously, intramuscularly and inside.
Fentanyl- a synthetic drug, superior in analgesic effect to morphine by 100-400 times. After intravenous administration, the maximum effect is observed after 1-3 minutes, which lasts 15-30 minutes. Fentanyl causes pronounced (up to respiratory arrest), but short-term depression of the respiratory center. Increases the tone of skeletal muscles. Bradycardia often occurs.
Indications for use: for neuroleptanalgesia in combination with neuroleptics (thalamonal or inovar). The drug can be used to relieve acute pain in myocardial infarction, angina pectoris, renal and hepatic colic. Recently, a transdermal fentanyl system has been used for chronic pain syndrome (valid for 72 hours).
Pentazocine hydrochloride- leads to less mental dependence, increases blood pressure.
Butorphanol(moradol) is similar in pharmacological properties to pentazocine. It is prescribed for severe pain, in the postoperative period, for cancer patients, in case of renal colic, injuries. Enter intramuscularly at 2-4 mg of a 0.2% solution or intravenously at 1-2 mg of a 0.2% solution.
Tramadol- a strong analgesic of the central action. There are two mechanisms of action associated with opioid receptors, due to which the sensation of pain is weakened, and also inhibits the reuptake of noradrenaline, as a result of which the transmission of pain impulses in the spinal cord is inhibited. Tramadol does not suppress respiration and does not cause dysfunction of the cardiovascular system. The action comes on quickly and lasts for several hours.
Indications for use: severe pain of various origins (due to trauma), pain after diagnostic and therapeutic procedures.
Side effects when using narcotic analgesics and measures to eliminate them:
Respiratory depression, as well as depression of the respiratory center in the fetus (in the umbilical vein - naloxone)
Nausea, vomiting (antiemetics - metoclopramide)
Increased smooth muscle tone (administered with atropine)
Hyperemia and itching of the skin (antihistamines)
Bradycardia
Constipation (laxative - senna leaves)
Tolerance;
Mental and physical dependence.
In acute poisoning with narcotic analgesics the function of the central nervous system is suppressed, characterized by loss of consciousness, slowing down of breathing until it stops, a decrease in blood pressure and body temperature. The skin is pale and cold, the mucous membranes are cyanotic. Characteristic features are pathological respiration of the Cheyne-Stokes type, preservation of the tendon reflex and pronounced miosis.
Treatment of patients with acute poisoning with narcotic analgesics:
Gastric lavage, regardless of the route of administration, with a 0.05-0.1% solution of potassium permanganate;
Reception of 20-30 g of activated carbon
Salt wash;
Intravenous and intramuscular administration of the naloxone antagonist (narcan). The drug acts quickly (1 min), but not for long (2-4 hours). For long-term action, nalmefene should be administered intravenously (10 hours are effective);
Artificial respiration may be necessary;
Warm up the patient.
If death does not occur in the first 6-12 hours, then the prognosis is positive, since most of the drug is inactivated.
With prolonged use of narcotic analgesics, drug dependence of the opioid type develops, which is characterized by tolerance, mental and physical dependence, as well as withdrawal symptoms. Tolerance appears after 2-3 weeks (sometimes earlier) with the introduction of the drug in therapeutic doses.
After stopping the use of opioid analgesics, tolerance to euphoria and respiratory depression decreases after a few days. Mental dependence - euphoria that occurs when using narcotic analgesics and is the root cause of uncontrolled drug use, especially quickly occurs in adolescents. Physical dependence is associated with withdrawal syndrome (withdrawal syndrome): lacrimation, hyperthermia, sudden changes in blood pressure, muscle and joint pain, nausea, diarrhea, insomnia, hallucinations.
The constant use of opioids leads to chronic poisoning, in which mental and physical performance decreases, exhaustion, thirst, constipation occur, hair falls out, etc.
Treatment of drug dependence on opioids is complex. These are methods of detoxification, the introduction of the opioid antagonist - naltrexone, symptomatic drugs and the implementation of measures to prevent the addict from contacting the familiar environment. However, a radical cure is achieved in a small percentage of cases. Most patients relapse, so preventive measures are important.
Pharmacosecurity:
- It must be remembered that narcotic analgesics are poisonous drugs of list A, they should be prescribed on special forms, they are subject to quantitative accounting. Extract and storage are regulated;
- For abuse, misuse - criminal liability;
- Morphine is not compatible in one syringe with chlorpromazine;
- Promedol is not compatible with antihistamines, tubocurarine, trazikor;
- The injectable form of tramadol is not compatible with solutions of diazepam, flunitrozenam, nitroglycerin;
- Do not inject pentazocine with barbiturates in the same syringe;
- Opium preparations inhibit intestinal motility and may delay the absorption of other drugs that are administered orally;
- Codeine in the composition of complex preparations practically does not cause addiction and addiction.
Narcotic analgesics
|
Name of the drug |
Release form |
Mode of application |
Higher doses and storage conditions |
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|
Morphine hydrochloride (Mogrpi pi hydrockloridum) |
Powder 1% solution in ampoules and syringe-tubes of 1 ml (10 mg / ml) |
Inside, 0.01-0.02 g after meals, subcutaneously, intramuscularly, 1 ml of a 1% solution, intravenously (slowly) |
WFD - 0.02 g, WDD - 0.05 g List A In a place protected from light |
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|
Codeine (Codeinum) |
Powder, tablets 0.015 g |
Inside, 0.01-0.02 g 3-4 times a day before meals |
VRD-0.05 g, VDD-0.2 List B In a dark place |
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|
Codeine Phosphate (Codeini phosphas) |
soluble |
Inside, 0.01-0.02 g 2-3 times in powders, mixtures |
VRD-0.1, VDC-0, Zg List B In a dark place |
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|
ethylmorphine hydrochloride (Aethylmor- phini hydrochlo- |
Powder, tablets of 0.01; 0.015 g |
Inside, 0.01-0.015 g 2-3 times a day; 1-2% solution, 1-2 drops in the conjunctival fissure |
VRD-0.03 g, VDD-0.1 List A In a dark place |
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|
Promedol (promedolum) |
Tablet powder, 0.025 g 1 (10 mg/ml) and 2% solution in ampoules and syringe-tubes according to 1 ml (20 mg/ml) |
Inside 0.025 g before meals subcutaneously, 1 ml of 1 or 2% solution |
List A In a tightly stoppered container |
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|
Fentanyl (Phentanylum) |
0.005% solution in ampoules of 2 and 5 ml (0.05 mg/ml) |
Intramuscularly and intravenously, 1-2 ml (0.00005-0.0001 g) |
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|
Antagonist of narcotic analgesics |
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|
Naloxone hydrochloride |
0.04% solution in 1 ml ampoules (0.4 mg/ml) |
Subcutaneously, intramuscularly, intravenously, b2 ml (0.0004-0.008 g) |
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Non-narcotic analgesics
Non-narcotic analgesics (analgesics-antipyretics) are drugs that eliminate pain during inflammatory processes and give antipyretic and anti-inflammatory effects.
Inflammation is a universal reaction of the body to the action of various (damaging) factors (causative agents of infections, allergic, physical and chemical factors).
The filling process involves various cellular elements (labrocytes, endothelial cells, platelets, monocytes, macrophages), which secrete biologically active substances: prostaglandins, thromboxane AZ, prostacyclin - inflammatory mediators. Enzymes of cyclookeigenase (COX) also contribute to the production of inflammatory mediators.
Non-narcotic analgesics block COX and inhibit the formation of prostaglandins, causing anti-inflammatory, antipyretic and analgesic effects.
The anti-inflammatory effect is that the exudative and proliferative phases of inflammation are limited. The effect is achieved in a few days.
Analgesic effect seen after a few hours. Drugs affect mainly pain in inflammatory processes.
Antipyretic effect manifests itself with hyperpyrexia after a few hours. At the same time, heat transfer increases due to the expansion of peripheral vessels and sweating increases. It is not advisable to reduce body temperature to 38 ° C, since subfebrile temperature is a protective reaction of the body (the activity of phagocytes and the production of interferon, etc. increase).
Salicylates
Acetylsalicylic acid(aspirin) - the first representative of non-narcotic analgesics. The drug has been used since 1889. It is available in tablets, it is part of such combined preparations as citramon, sedalgin, cofitsil, alka-seltzer, jaspirin, tomapirin, etc.
Indications for use: as an analgesic and antipyretic (for fever, migraine, neuralgia) and as an anti-inflammatory agent (for rheumatism, rheumatoid arthritis); the drug has an antiaggregatory effect, it is prescribed for the prevention of thrombotic complications in patients with myocardial infarction, cerebrovascular accidents and other cardiovascular diseases.
Side effect irritation of the gastric mucosa, stomach pain, heartburn, ulcerogenic effect (formation of stomach ulcers), Reye's syndrome.
Soluble form of aspirin - acelysin.
It is administered intramuscularly and intravenously as an anesthetic in the postoperative period, with rheumatic pain, oncological diseases.
Sodium salicylate as an analgesic and antipyretic, it is prescribed orally after meals for patients with acute rheumatism and rheumatoid endocarditis, sometimes administered intravenously.
Derivatives of pyrazolone and indoloctic acid
Analgin(metamizol-sodium) - has a pronounced analgesic, anti-inflammatory and antipyretic effect.
Indications for use: with pain of various origins (headache, toothache, trauma pain, neuralgia, radiculitis, myositis, fever, rheumatism). Assign inside after a meal for adults, and also administered intramuscularly and intravenously.
Side effect edema, increased blood pressure, toxic effects on hematopoiesis (blood count changes).
Butadion(hair dryer and forehead and zones) - has an analgesic, antipyretic and anti-inflammatory effect. The anti-inflammatory effect of butadione is more pronounced than in salicylates.
Assign for arthritis of various etiologies, acute gout. Applied orally during or after meals. The duration of the course of treatment is from 2 to 5 weeks. With thrombophlebitis of the superficial veins, butadione ointment is used, but due to the large number of side effects in our time, the use of butadione is limited.
Indomethacin(metindol) - has a pronounced analgesic, anti-inflammatory and antipyretic effect. Assign to patients with rheumatoid arthritis, osteoarthritis, gout, thrombophlebitis. Applied inside, and indomethacin ointment is rubbed with acute and chronic polyarthritis, sciatica.
Para-aminophenol derivatives
Paracetamol(panadol, efferalgan, tylenol) - according to the chemical structure, it is a metabolite of phenacetin and gives the same effects, but is less toxic compared to phenacetin. Used as an antipyretic and analgesic. Abroad, paracetamol is produced in various dosage forms: tablets, capsules, mixtures, syrups, effervescent powders, as well as in the composition of such combined preparations as coldrex, solpadein, pa on dol-extra.
Derivatives of alkanoic acids
diclofenac sodium (ortofen, voltaren) is an active anti-inflammatory agent. It has a pronounced analgesic effect, and also has antipyretic activity. The drug is well absorbed from the digestive tract, almost completely bound to plasma proteins. Excreted in urine and bile as metabolites. The toxicity of diclofenac sodium is low, the drug is characterized by a significant breadth of therapeutic action.
Indications for use: rheumatism, rheumatoid arthritis, arthrosis, spondylarthrosis and other inflammatory and degenerative diseases of the joints, postoperative and post-traumatic edema, neuralgia, neuritis, pain syndrome of various origins as an adjuvant in the treatment of 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, increases the range of motion in them.
Indications for use: rheumatoid arthritis, osteoarthritis, gout, inflammatory diseases of the musculoskeletal system, pain syndrome.
Naproxen(naproxia) - a drug that is inferior in anti-inflammatory effect to diclofenac sodium, but exceeds its analgesic effect. It has a longer effect, so naproxen is prescribed 2 times a day.
Preparations of a chemical structure
Ketorolac(ketanov) has a pronounced analgesic activity, significantly superior to the activity of other non-narcotic analgesics. Less pronounced are antipyretic and anti-inflammatory effects. The drug blocks COX-1 and COX-2 (cyclooxygenase) and thus prevents the formation of prostaglandins. Assign adults and children over 16 years of age inside with injuries, toothache, myalgia, neuralgia, sciatica, dislocations. It is administered intramuscularly for pain in the postoperative and post-traumatic periods, injuries, fractures, dislocations.
Side effects: nausea, vomiting, stomach pain, liver dysfunction, headache, drowsiness, insomnia, increased blood pressure, palpitations, allergic reactions.
Contraindications: period of pregnancy and lactation, children under 16 years of age. Carefully appoint patients with bronchial asthma, impaired liver function, heart failure.
Mefenamic acid- inhibits the formation and eliminates inflammation from tissue depots of mediators (serotonin, histamine), inhibits the biosynthesis of prostaglandins, etc. The drug enhances cell resistance to damaging effects, well eliminates acute and chronic toothache and pain in muscles and joints; exhibits an antipyretic effect. Unlike other anti-inflammatory drugs, it almost does not show an ulcerogenic effect.
Sodium mefenaminate- similar in action to mefenamic acid. When applied topically, it accelerates the healing of wounds and ulcers.
Indications for use: ulcerative stomatitis, periodontal disease, toothache, sciatica.
Piroxicam- anti-inflammatory agent with analgesic and antipyretic effects. Inhibits the development of all symptoms of inflammation. It is well absorbed from the digestive tract, binds to blood plasma proteins, and acts for a long time. It is excreted mainly by the kidneys.
Indications for use: osteoarthritis, spondylarthrosis, rheumatoid arthritis, sciatica, gout.
Meloxicam(Movalis) - selectively blocks COX-2 - an enzyme that is formed in the focus of inflammation, as well as COX-1. The drug has a pronounced anti-inflammatory, analgesic and antipyretic effect, and also eliminates local and systemic symptoms of inflammation, regardless of location.
Indications for use: for symptomatic therapy of patients with rheumatoid arthritis, osteoarthritis, arthrosis with severe pain syndrome.
In recent years, drugs with a greater selective effect than meloxicam have been created. Thus, the drug celecoxib (Celebrex) is hundreds of times more active in blocking COX-2 than COX-1. A similar drug - rofecoxib (Viox) - selectively blocks COX-2.
Side effects of non-narcotic analgesics
Irritation of the mucous membrane of the digestive tract, ulcerogenic effect (especially when using acetylsalicylic acid, indomethacin, butadione)
Edema, fluid and electrolyte retention. Occur 4-5 days after taking the drug (especially butadione and indomethacin)
Reye's syndrome (hepatogenic encephalopia) is manifested by vomiting, loss of consciousness, coma. May occur in children and adolescents due to the use of acetylsalicylic acid for influenza and acute respiratory infections;
Teratogenic effect (acetylsalicylic acid and indomethacin should not be prescribed in the first trimester of pregnancy)
Leukopenia, agranulocytosis (especially in pyrazolone derivatives)
Retinopathy and keratopathy (due to deposition of indomethacin in the retina)
allergic reactions;
Hepato- and nephrotoxicity in paracetamol (with prolonged use, especially at high doses);
hallucinations (indomethacin). With caution appoint patients with mental disorders, with epilepsy and parkinsonism.
Pharmacosecurity:
- It is necessary to explain to the patient that the uncontrolled use of drugs that are potent substances is harmful to the body;
- To prevent the damaging effect of drugs on the mucous membranes, the patient should be taught to take drugs correctly (with food, milk or a full glass of water) and recognize the signs of gastric ulcer (not digesting food in the stomach, vomiting "coffee grounds", tarry stools);
- To prevent the development of agranulocytosis, it is necessary to monitor the blood test, warn the patient about the need to inform the doctor in case of symptoms of agranulocytosis (feeling cold, fever, sore throat, malaise)
- To prevent nephrotoxicity (hematuria, oliguria, crystalluria), it is necessary to control the amount of urine output, warn the patient about the importance of informing the doctor if any symptoms appear
- Remind the patient that in case of drowsiness after taking indomethacin, one should not drive a car and work with dangerous equipment;
- Non-narcotic analgesics are not compatible with sulfa drugs, antidepressants, anticoagulants;
- Salicylates should not be prescribed together with other non-paranotic analgesics (increased ulcerogenic action) and anticoagulants (increased risk of bleeding).
21. Non-narcotic analgesics and antipyretics.
The mechanism of analgesic action of non-narcotic analgesics.
Inhibition of cyclooxygenase → inhibition of the synthesis of prostaglandins PG E 2 , PG F 2α , PGI 2 → prostaglandins that cause hyperalgesia (increased sensitivity of nociceptors to chemical and mechanical stimuli) are not synthesized → prevention of hyperalgesia, an increase in the sensitivity threshold of neurons to pain stimuli.
The mechanism of antipyretic action of non-narcotic analgesics.
Inhibition of cyclooxygenase COX-2 → inhibition of the synthesis of fever mediators (mainly PG E 1) → a decrease in the pyrogenic effect of fever mediators on the thermoregulatory center of the hypothalamus → antipyretic effect
Indications for the use of non-narcotic analgesics.
headache and toothache, postoperative pain
rheumatic diseases, arthralgia, myalgia
non-rheumatic diseases of the musculoskeletal system, injuries
neurological diseases (neuralgia, sciatica)
dysmenorrhea (algomenorrhea)
NB! Non-narcotic analgesics are not effective for visceral pain (myocardial infarction, renal colic, acute abdomen, etc.) and do not eliminate the emotional component of pain (fear, anxiety, agitation), unlike narcotic analgesics.
Contraindications to the use of non-narcotic analgesics.
erosive and ulcerative lesions of the gastrointestinal tract, especially in the acute stage
severe impairment of liver and kidney function
cytopenia
individual intolerance
pregnancy
Side effects of non-narcotic analgesics.
dyspeptic disorders (abdominal pain, nausea, vomiting)
erosions and ulcers of the stomach and duodenum, bleeding and perforation (as a result of systemic inhibition of COX-1)
negative effect on kidney function (direct effect, vasoconstriction and decrease in renal blood flow → renal ischemia, impaired renal function, hypernatremia, hyperkalemia, increased blood pressure, interstitial nephritis)
hematotoxicity (aplastic anemia, agranulocytosis)
hepatotoxicity (changes in transaminase activity, jaundice, sometimes drug-induced hepatitis)
hypersensitivity reaction (angioedema, anaphylactic shock, bronchospasm)
neurotoxicity (headache, dizziness, impaired reflex reactions)
Reye's syndrome: encephalopathy, cerebral edema, liver damage ( in children with viral infections when they are prescribed aspirin)
Comparative characteristics of narcotic and non-narcotic analgesics.
|
Properties |
Narcotic analgesics |
Non-narcotic analgesics |
|
Analgesic action |
Moderate |
|
|
Preferential localization of analgesic action |
Central nervous system |
Peripheral nervous system (excluding aniline derivatives) |
|
hypnotic action | ||
|
Antipyretic action |
Minor |
Expressed |
|
Respiratory depression | ||
|
Anti-inflammatory action |
+ (excluding aniline derivatives) |
|
|
addictive | ||
|
drug addiction |
Acetylsalicylic acid, ibuprofen, paracetamol, nefopam, keterolac, tramadol.
Acetylsalicylic acid (Acidum acetylsalicylicum).
Salicylic ester of acetic acid.
Synonyms: Aspirin, Aspro, Acesal, Aceticyl, Acetol, Acetophen, Acetosal, Acetylin, Acetylsal, Acetysal, Acylpyrin, Aspirin, Aspisol, Asposal, Aspro, Astrin, Ataspin, Bayaspirin, Bebaspin, Benaspir, Bispirine, Caprin, Cetasal, Citopyrine, Clariprin, Darosal, Durasal, Easprin, Endosalil, Endospirin, Eutosal, Genasprine, Helicon, Isopirin, Istopirin, Monasalyl, Novosprin, Panspiril, Polopiryna, Prodol, Rodopyrin, Ruspirin, Salacetin, Saletin, Temperal, Vicapirine, Zorprin, etc.
Acetylsalicylic acid has an anti-inflammatory, antipyretic, and analgesic effect, and it is widely used for fever, headache, neuralgia, etc., and as an antirheumatic agent.
The anti-inflammatory effect of acetylsalicylic acid (and other salicylates) is explained by its influence on the processes occurring in the focus of inflammation; a decrease in capillary permeability, a decrease in hyaluronidase activity, a restriction of the energy supply of the inflammatory process by inhibiting the formation of ATP, etc. Inhibition of prostaglandin biosynthesis is important in the mechanism of anti-inflammatory action.
The antipyretic effect is also associated with the effect on the hypothalamic centers of thermoregulation.
The analgesic effect is due to the effect on the centers of pain sensitivity, as well as the ability of salicylates to reduce the algogenic effect of bradykinin.
Acetylsalicylic acid is widely used as an anti-inflammatory, antipyretic and analgesic agent. It is used alone and in combination with other drugs. There are a number of finished medicines containing acetylsalicylic acid (tablets<<Цитрамон>>, <<Кофицил>>, <<Асфен>>, <<Аскофен>> etc.).
Recently, injectable preparations have been obtained, the main active principle of which is acetylsalicylic acid (see Acelizin, Aspizol).
In the form of tablets, acetylsalicylic acid is prescribed orally after meals.
Acetylsalicylic acid is an effective, quite affordable tool that is widely used in outpatient practice. It should be borne in mind that the use of the drug should be carried out with the observance of precautionary measures due to the possibility of a number of side effects.
When using the drug, profuse sweating may develop, tinnitus and hearing loss, angioedema, skin and other allergic reactions may appear.
It is important to consider that with prolonged (without medical supervision) use of acetylsalicylic acid, side effects such as dyspeptic disorders and gastric bleeding may occur; the mucous membrane of not only the stomach, but also the duodenum can be affected.
The so-called ulcerogenic effect is characteristic to varying degrees of various anti-inflammatory drugs: corticosteroids, butadione, indomethacin, etc. The appearance of stomach ulcers and gastric bleeding when using acetylsalicylic acid is explained not only by the resorptive effect (inhibition of blood coagulation factors, etc.), but also by its direct irritant effect on the gastric mucosa, especially if the drug is taken in the form of unground tablets. This also applies to sodium salicylate.
To reduce the ulcerogenic effect and gastric bleeding, acetylsalicylic acid (and sodium salicylate) should be taken only after meals, it is recommended that the tablets be carefully crushed and washed down with plenty of liquid (preferably milk). There are, however, indications that gastric bleeding can also be observed when taking acetylsalicylic acid after meals. Sodium bicarbonate contributes to a more rapid release of salicylates from the body, however, to reduce the irritating effect on the stomach, they resort to taking mineral alkaline waters or sodium bicarbonate solution after acetylsalicylic acid.
Abroad, acetylsalicylic acid tablets are often produced from a finely crystalline powder with alkalizing (buffer) additives.
Peptic ulcer of the stomach and duodenum and gastrointestinal bleeding are contraindications to the use of acetylsalicylic acid and sodium salicylate. The use of acetylsalicylic acid is also contraindicated in a history of peptic ulcer, portal hypertension, venous congestion (due to a decrease in the resistance of the gastric mucosa), and in violation of blood coagulation.
With prolonged use of salicylates, the possibility of developing anemia should be considered and systematically perform blood tests and check for the presence of blood in the feces.
Due to the possibility of allergic reactions, caution should be exercised when prescribing acetylsalicylic acid (and other salicylates) to persons with hypersensitivity to penicillins and other<<аллергогенным>> medicines.
With increased sensitivity to acetylsalicylic acid, aspirin asthma may develop, for the prevention and treatment of which methods of desensitizing therapy have been developed using increasing doses of aspirin.
In connection with the available experimental data on the teratogenic effect of acetylsalicylic acid, it is recommended not to prescribe it and its preparations to women in the first 3 months of pregnancy.
Recently, there have been reports of the possible danger of using acetylsalicylic acid in children to reduce body temperature in influenza, acute respiratory and other febrile diseases in connection with observed cases of Ray's syndrome (hepatogenic encephalopathy). It is recommended to replace acetylsalicylic acid with paracetamol.
An essential feature of acetylsalicylic acid, which has recently become of great importance, is the ability of the drug to have an antiaggregatory effect, to inhibit spontaneous and induced platelet aggregation.
Substances that have an antiaggregatory effect have become widely used in medicine for the correction of hemorheological disorders and the prevention of thrombotic complications in patients with myocardial infarction, cerebrovascular accidents and other cardiovascular diseases. In this regard, it is now appropriate to single out these substances in a separate group of antiaggregants. These properties of acetylsalicylic acid are discussed in the appropriate section (see Antiaggregatory agents).
Due to the effect on platelet aggregation, as well as some anticoagulant activity, blood tests should be carried out periodically during treatment with acetylsalicylic acid. With bleeding disorders, especially with hemophilia, bleeding may develop. For early detection of ulcerogenic action, it is necessary to periodically examine the feces for the presence of blood.
It should be borne in mind that under the influence of acetylsalicylic acid, the action of anticoagulants (derivatives of coumarin, heparin, etc.), sugar-lowering drugs (derivatives of sulfonylurea), increases the risk of gastric bleeding with the simultaneous use of corticosteroids and non-steroidal anti-inflammatory drugs, and the side effects of methotrexate increase. The effect of furosemide, uricosuric agents, spironolactone is somewhat weakened.
IBUPROFEN (Ibuprofenum). d, 1-2-(4-Isobutylphenyl) propionic acid.
Synonyms: Brufen, Algofen, Anflagen, Artofen, Artril, Brufanic, Brufen, Bufigen, Burana, Dolgit, Ebufac, Iborufen, Ibumetin, Inflam, Lamidon, Mortifen, Motrin, Napacetin, Nobfen, Nuprin, Nurofen, Paxofen, Rebugen, Relcofen, Reumafen, Ruprin, Seclodin, Sednafen, etc.
The drug is one of the modern non-steroidal anti-inflammatory drugs. It has anti-inflammatory, analgesic and moderate antipyretic activity.
In the mechanism of action of ibuprofen, its inhibitory effect on the biosynthesis of prostaglandins plays a significant role.
There is evidence of the stimulating effect of ibuprofen on the formation of endogenous interferon (see Interferons) and its ability to have an immunomodulatory effect and improve the index of nonspecific resistance of the body.
Ibuprofen has a more pronounced effect in rheumatoid arthritis in the initial stages of the inflammatory process without abrupt changes in the joints. In terms of strength of action, it is somewhat inferior to ortofen, indomethacin, but it is better tolerated.
It is used to treat rheumatoid arthritis, deforming osteoarthritis, ankylosing spondylitis and in various forms of articular and extra-articular rheumatoid diseases, as well as pain in some inflammatory lesions of the peripheral nervous system.
The drug is usually well tolerated, without causing irritation of the gastric mucosa, which is considered as its main advantage compared to salicylates. In some cases, however, heartburn, nausea, vomiting, flatulence, and skin allergic reactions are possible. With severe side effects, reduce the dose or stop taking the drug.
Ibuprofen is contraindicated in acute ulcers and exacerbations of gastric and duodenal ulcers, ulcerative colitis, increased individual sensitivity to the drug, as well as in diseases of the optic nerve.
Caution should be observed when prescribing the drug to persons who have had gastric and duodenal ulcers in the past, with gastritis, enteritis, colitis, chronic hepatitis, cirrhosis of the liver.
PARACETAMOL (Paracetamolum). para-acetaminophenol.
Synonyms: Opradol, Panadol, Ushamol, Abesanil, Acelifen, Acemol, Acetalgin, Acetaminophen, Acetaminophenol, Actasol, Algotropyl, Alvedon, Aminophen, Amphenol, Apagan, Apamide, Apanol, Biocetamol, Celifen, Cetadol, Cetanil, Chemcetaphen, Dapirex, Datril, Dexamol, Dimindol, Dolamin, Dolanex, Dolipram, Efferalgan, Erocetamol, Febridol, Febrinil, Febrinol, Fendon, Metamol, Minoset, Myalgin, Napamol, Naprinol, Nasprin, Nysacetol, Opradol, Pacemol, Panadol, Panadon, Paracinol, Paramol, Pyrenol, Pyrinazin, Rolocin, Tempramol, Tralgon, Tylemin, Tylenol, Ushamol, Valadol, Valgesic, Valorin, Volpan, Winadol, etc.
Paracetamol is chemically close to phenacetin. It is the main metabolite that is rapidly formed in the body when taking phenacetin; apparently, causes the analgesic effect of the latter. In terms of analgesic activity, paracetamol does not differ significantly from phenacetin; like phenacetin, it has weak anti-inflammatory activity. The main advantages of paracetamol are less toxicity, less ability to cause the formation of methemoglobin. However, this drug may also cause side effects; with prolonged use, especially in large doses, paracetamol can have nephrotoxic and hepatotoxic effects.
Paracetamol is absorbed in the upper intestine, metabolized in the liver, excreted mainly by the kidneys.
Indications for use are the same as for amidopyrine and phenacetin.
When using paracetamol, you should monitor the function of the liver, the state of the hematopoietic system; allergic reactions are possible.
TRAMADOL (Tramadolum). (#)-trans-2-[(Dimethylamino)methyl] 1-(m-methoxyphenyl) cyclohexanol hydrochloride.
Synonyms: Tramal, Crispin, Melanate, Tramadol hydrochloride, Tramal.
It has a strong analgesic activity, gives a quick and lasting effect. Inferior, however, in activity to morphine at the same doses (it is used, respectively, in large doses).
It belongs to the group of agonists-antagonists. Effective when administered orally and parenterally.
When administered intravenously, it has an analgesic effect after 5-10 minutes, when administered orally, after 30-40 minutes. Valid for 3-5 hours.
It is used for severe acute and chronic pain: in the postoperative period, with injuries, in cancer patients, etc., as well as before operations. For mild pain, the drug is not recommended.
You can prescribe tramadol in the form of rectal suppositories.
For children under the age of 14, the drug is not prescribed due to insufficient knowledge (the drug has been relatively recently introduced into medical practice). The drug should not be used for a long time (to avoid addiction).
Tramadol is relatively well tolerated, does not cause significant respiratory depression at usual doses, and does not significantly affect blood circulation and the gastrointestinal tract. May, however, cause nausea, vomiting, dizziness, sweating; high blood pressure may decrease slightly.
Tramadol should not be prescribed for acute alcohol intoxication; patients with hypersensitivity to narcotic analgesics; patients taking MAO inhibitors. Pregnant women should be administered with extreme caution.
| " |
Non-narcotic analgesics can reduce the activity of an enzyme that causes pain. Most drugs are also able to have a decongestant effect. After taking non-narcotic energy drinks, the vessels expand, which leads to an increase in 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 analgesics drugs are listed below:
1. Analgin is the first medicine that comes to mind at the mention of analgesics. It belongs to the pyrazolone derivatives 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 save from headaches.
3. Pyramidone is a strong non-narcotic analgesic, which is usually prescribed for rheumatic pains.
4. Citramon and aspirin are another pair of well-known analgesics. Means help get rid of headaches of various origins, including pressure.
5. Ibuprofen is a powerful pain reliever that can relieve pain of any kind.
Askafen, Asfen, Butadione, Phenacetin, Indomethacin, Naproxen are all non-narcotic analgesics, and the list can be continued for a long time.
It is not easy to name the most powerful non-narcotic analgesic. Everyone chooses for himself a “duty” analgesic, depending on the characteristics of the organism: for some, an aspirin tablet will be enough to get rid of a headache, while others have to save themselves with something no weaker than ibuprofen.
The main thing is not to get carried away. It is one thing if analgesics are drunk once every five years “on a special occasion”, and quite another when the pills are swallowed daily. The specialist will probably be able to suggest a safer solution to the problem, well, or help you choose the most suitable analgesic.
Non-narcotic analgesics
Non-narcotic analgesics are drugs that reduce the perception of pain without a noticeable disruption of other functions of the central nervous system and are devoid (unlike narcotic analgesics) of a psychotropic effect (and hence narcogenicity), a depressing effect on the nerve centers, which allows them to be used more widely and for a long time. However, their analgesic effect is much weaker, and with 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 the 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 ways (they do not affect the ability of the central nervous system to summation of subcortical impulses).
The 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 tissues is not the same for different drugs, the severity of the above effects varies greatly. On this basis, they are divided into antipyretic analgesics (simple analgesics) and antiphlogistic analgesics, 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) in the urine, to a lesser extent in the bile.
Analgesic and antipyretic effects develop rapidly; anti-inflammatory and desensitizing action - slower; it requires large doses. This increases the risk of developing complications associated with inhibition of prostaglandin synthesis (sodium retention, edema, ulceration, bleeding, etc.), with a direct toxic effect of certain chemical groups on tissues (inhibition of hematopoiesis, methemoglobinemia, etc.), allergic and paraallergic (" aspirin asthma", "aspirin triad") reactions. During pregnancy, prostaglandin synthesis inhibitors can inhibit and delay labor, and contribute to premature closure of the ductus arteriosus. In the first trimester, they are usually not prescribed due to the danger of pathogenic action (although for most drugs the absence of teratogenicity has been proven in animals). In recent years, drugs have appeared that inhibit both cyclooxygenase (the synthesis of prostaglandins, thromboxane, prostacyclin) and lipoxygenesis (the 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 thiaprofen, which rarely causes bronchospasm, gastric ulcers and edema associated with PG F2 deficiency; COX-2 inhibitors nise (nimesulide).
Non-steroidal anti-inflammatory drugs (NSAIDs)) is used for pain and inflammation of the 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, antipsychotics 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, preparations of groups 4-8 have a high anti-inflammatory and desensitizing activity (see classification). Aniline derivatives are devoid of anti-inflammatory activity, pyrazolone as an NSAID is rarely used, since they inhibit hematopoiesis and have a small breadth of therapeutic action.
Contraindications to the use of NSAIDs are allergic and paraallergic reactions to them, gastric ulcer, diseases of the hematopoietic system, I trimester of pregnancy.
Classification of non-narcotic analgesics
I. Salicylic acid derivatives: 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). Preparations of 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, they inhibit hematopoiesis, therefore they 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 the treatment of hyperthermia, amidopyrine increases convulsive readiness in young children and reduces diuresis.
III. Para-aminophenol derivatives: phenacetin and paracetamol. Representatives of this group are deprived of anti-inflammatory activity, antiplatelet and antirheumatic action. Practically do not cause ulceration, do not inhibit kidney function, do not increase convulsive activity of the brain. Paracetamol is the drug of choice in the treatment of hyperthermia, especially in children. Phenacetin with prolonged use causes nephritis.
IV. Indolacetic acid derivatives: indomethacin, sulindac, selective COX-2 inhibitor - stodolac. Indomethacin is the standard in terms of anti-inflammatory activity (maximum), but interferes with the metabolism of brain mediators (reduces GABA levels) and provokes insomnia, agitation, hypertension, convulsions, exacerbation of psychosis. Sulindac turns into indomethacin in the patient's body, has a longer and slower action.
V. Derivatives of phenylacetic acid: diclofenac sodium (ortofen, voltaren). This drug rarely causes ulceration and is mainly used as an anti-inflammatory and antirheumatic agent.
VI. Propionic acid derivatives: ibuprofen, naproxen, pirprofen, thiaprofenic acid, ketoprofen. Ibuprofen is similar to diclofenac; naproxen and pyroprofen give a greater anti-inflammatory effect; thiaprofen shows greater selectivity in suppressing the synthesis of PG F2-alpha (less often it has a side effect on the bronchi, gastrointestinal tract and uterus).
VII. Derivatives of fenamic (anthranilic) acid: mefenamic acid, flufenamic acid. Mefenamic acid is used primarily as an analgesic and antipyretic; flufenamic - as an anti-inflammatory agent (weak analgesic).
VIII. Oxicams: piroxicam, loroxicam (xefocam), tenoxicam, selective COX-2 inhibitor meloxicam. The drugs differ in the duration (12-24 hours) of action and the ability to penetrate well into inflamed tissues.
IX. Various drugs. Selective COX-2 inhibitors - nabulitone, nimesulide (nise), niflumic acid - are similar in their properties to mefenamic acid; highly active COX-2 inhibitors - celecoxib (celebrex), viox (difiunisal - a salicylic acid derivative) - have a prolonged anti-inflammatory and analgesic effect.
A derivative of pyrrolysinecarboxylic acid - ketorolac (ketorol) - has a pronounced analgesic effect.
X. Various drugs that have an anti-inflammatory effect: dimexide, mefenamin sodium salt, medical bile, bitofit. 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.
17SLEEPING SUBSTANCES IN VETERINARY SECTORITY
Sleeping pills
Sleeping pills promote falling asleep and provide the necessary duration of sleep.
Animals deprived of sleep die in 4-6 days, while without food they can live for 2-3 weeks or more.
All sleeping pills are divided into 3 groups:
1. short duration of action (ensure the process of falling asleep);
2. medium duration of action (promote falling asleep and support sleep in its first hours);
3. long-acting (provide the entire duration of sleep).
Sleeping pills are often used for premedication, enhancing the action of anesthetics, 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 certain localization of action.
Drugs with hypnotic activity are classified based on the principle of their action and chemical structure:
1. benzodiazepine derivatives;
2. derivatives of barbituric acid;
3. aliphatic compounds.
- Benzodiazepine derivatives (nitrazepam, diazepam, phenazepam, etc.)
Their main action is to eliminate mental stress, and the coming calm contributes to the development of sleep.
They have a hypnotic, sedative, anticonvulsant, muscle-relaxing effect.
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 the suppression of polysynaptic spinal reflexes.
The anticonvulsant effect is the result of the activation of the inhibitory processes of the brain, implemented through GABA. This increases the flow of chloride ions into neurons, which leads to an increase in the inhibitory postsynaptic potential.
Derivatives of barbituric acid.
Depending on the strength and duration of action, barbiturates are conditionally divided into 3 groups:
1. short-acting - hexenal, sodium thiopental (used for short-term anesthesia);
2. medium duration of action - barmamil, sodium etaminal, cyclobarbital (hypnotics). Causes sleep lasting 5 - 6 hours, in large doses - anesthesia (in small animals).
3. Long lasting
Mechanism of action. Barbiturates inhibit the reticular formation of the midbrain, reduce the excitability of the sensory and motor areas 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, which is a mediator of inhibition, into the synoptic cleft.
In addition, barbiturates reduce the sodium permeability of neuronal membranes and inhibit the respiration of the mitochondria of the nervous tissue.
Barbiturates of average and long action are considered true hypnotics.
All barbiturates are white or some shades of crystalline powders, poorly soluble in water, have acidic properties.
Contraindicated in diseases of the liver and kidneys, sepsis, fever, caesarean section, severe circulatory disorders, respiratory diseases.
The imported drug rompun has become widely used in surgery.
After intramuscular or intravenous administration, depending on doses, animals are observed to calm down and sleep with relaxation of skeletal muscles and severe anesthesia.
21 NEUROLEPTICS
The antipsychotic effect of neuroleptics differs in the following external manifestations:
the depth and duration of the calm they cause;
the severity of the activation of human (animal) behavior after the application of the agent;
antidepressant effect.
It goes without saying that the preference for one or another drug is given depending on the goals pursued by the doctor. So, for example, if it is required to weaken the stress response during animal transportation, there are more hopes for drugs with sedative properties, but if it is necessary to smooth out tense rank conflicts without weakening eating behavior, agents with activating effects are desirable.
The mechanism of action of neuroleptics is complex, and in explaining it it is difficult to determine which changes in the brain are primary and which are secondary. Nevertheless, in the action of most drugs in this group, general patterns were revealed.
Antipsychotics, 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 intervene in the transmission of excitation along adrenergic, dopaminergic, cholinergic and other synapses and, depending on this, cause certain effects. Thus, sedative and anti-stress effects can be associated with the blockade of adrenoreactive systems of the reticular formation, accumulation in the central synapses of the inhibitory mediator - GABA; antipsychotic - with the suppression of dopaminergic processes in the limbic system; autonomic disorders (weakening of the motility of the gastrointestinal tract and secretion of glands) - with a 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.
Antipsychotics inhibit the release of corticotropin- and somatotropin-releasing factors by the hypothalamus, and this underlies the mechanism for preventing stressful shifts in carbohydrate and mineral metabolism in the body.
Antipsychotics, both parenterally and orally, are well absorbed into the blood, penetrate the blood-brain barrier. Most of all, they accumulate in the liver, where they undergo transformation, after which, unchanged or transformed, they are excreted from the body mainly through the kidneys.
Allergy may develop to antipsychotics, some of them irritate tissues, with prolonged use 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 effect of the cerebral cortex on the motor centers of the subcortex). However, the risk 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, and lithium salts.
Derivatives of phenothiazines.
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 (triftazine, mepazine) crystalline powders with a greenish-yellow tint. Easily soluble in water, 95% alcohol, chloroform, practically insoluble in ether and benzene. Easily oxidized and darken in the 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!). With intramuscular injections, painful infiltrates are possible, and with rapid introduction into a vein, damage to the epithelium. Therefore, the drugs are diluted in solutions of novocaine, glucose, isotonic sodium chloride solution.
Cause photosensitivity in animals; in addition to neuroleptic action - muscle relaxation, reduce body temperature; block the trigger zone of the vomiting center and prevent or remove the development of the emetic effect mediated through this zone (for example, from apomorphine, arecoline, etc.), do not act antiemetic if the vestibular apparatus and the gastric mucosa are irritated; depress the cough center, eliminate hiccups.
Aminazin. White or creamy white fine crystalline powder, easily soluble in water; has bactericidal properties, so the solutions are prepared in boiled distilled water without subsequent sterilization.
In chlorpromazine, the central adrenolytic effect is well expressed. It blocks the impulse coming from the extero- than from the interoreceptors more strongly: it prevents neurogenic gastric ulcers that occur during immobilization and electrical stimulation of rats, but does not affect their development when the duodenum is traumatized; reduces the time between the end of feed intake and the beginning of the ruminant period and prevents the termination of ruminant cycles in sheep after strong skin electrical irritation. Sensitivity to chlorpromazine in horses is higher than in cattle.
Applied inside and intramuscularly: as an anti-stress agent for various manipulations with animals; for premidication and potentiation of the action of analgesics, anesthetics, hypnotics and anticonvulsants; before manipulations to eliminate blockage of the esophagus in ruminants (in emergency cases, it can be administered intravenously), reduction of joint dislocations; with self-gnawing and hypogalactia in fur-bearing animals; as an antiemetic in deworming dogs with arecoline.
After the use of chlorpromazine in slaughter animals, it is most found in the lungs, kidneys and liver. In the muscles, residual amounts persist for 12-48 hours.
Levomepromazine (tizercin). Potentiates anesthetics and analgesics stronger than chlorpromazine, but acts weaker than it as an antiemetic. It acts more on noradreno- than on dopamine receptors. Side effects are less pronounced.
Etaperazine. It is better tolerated and has a stronger antiemetic effect than chlorpromazine, but is less suitable for premedication.
Triftazin. The most active neuroleptic. The sedative effect is stronger than chlorpromazine, and the adrenolytic effect is weaker. It does not have antihistamine, anticonvulsant and antispasmodic effects. It inhibits the peristalsis of the gastrointestinal tract in ruminants more than in animals of other species. Less damage to the liver.
Fluorphenazine decanoate. A drug with a moderately pronounced sedative effect, blocks more dopamine than norepinephrine receptors. Its antipsychotic effect is combined with an activating one. It is of interest for animal testing as a long-acting antipsychotic (a single injection is effective for 1-2 weeks or more).
Derivatives of butyrophenone.
The peculiarity of the pharmacodynamics of this group of drugs is that they have strongly pronounced antipsychotic and stimulating properties, while sedative and hypothermic properties are weaker. More specific than other antipsychotics, they act on the cerebral cortex, enhancing the processes of inhibition in it. This, apparently, is explained by the great affinity of their chemical structure to GABA, the inhibitory mediator of the cerebral cortex. The main disadvantage is the possibility of extrapyramidal disorders. However, these disorders occur from high doses. Studies have shown that butyrophenones (haloperidol) are promising for use in veterinary medicine as anti-stress and promote the growth of young animals. The latter, apparently, is associated with 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 of weight): inside 0.07-0.1 and intramuscularly 0.045-0.08 to prevent transport stress in calves.
Of the other butyrophenones, trifluperidol is of interest (more active than haloperidol in psychotic action), droperidol (acts strongly, quickly, but not for long).
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 kutrovy family, grows in South and Southeast Asia (India, Sri Lanka). The plant, especially in the roots, contains a large amount of alkaloids (reserpine, aymalicin, serpin, etc.), which act as a sedative, hypotensive (reserpine) or adrenolytic (aymalicin, etc.).
Under the influence of rauwolfia alkaloids, especially reserpine, animals calm down and physiological sleep deepens, interoreceptive reflexes are inhibited. The hypotensive effect is quite pronounced, and therefore the drugs are widely used in medicine for hypertension. The hypotensive effect develops gradually, maximally after a few days.
Unlike chlorpromazine, reserpine (one of the main rauwolfia alkaloids) does not have an adrenolytic effect and at the same time causes a number of cholinomimetic effects: slowing of cardiac activity, increased motility of the gastrointestinal tract, etc. It does not have a ganglioblocking effect.
Of the mechanisms of action, a violation of the norepinephrine deposition process 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 weakens. Norepinephrine reuptake does not appear to be affected by reserpine. Reserpine reduces the content of norepinephrine, dopamine and serotonin in the central nervous system, as the transport of these substances from the cellular plasma is blocked and they are deaminated. As a result, reserpine acts depressingly on the central nervous system. Animals become less active and less responsive to exogenous stimuli. The effect of sleeping pills and narcotic substances is enhanced.
Under the influence of reserpine, the content of catecholamines in the heart, blood vessels and other organs decreases. As a result, cardiac output, total peripheral vascular resistance and arterial blood pressure decrease. The influence of reserpine on the vasomotor center is denied by most authors. Along with a decrease in blood pressure, kidney function improves: blood flow increases and glomerular filtration increases.
Secretion and motility of the gastrointestinal tract are enhanced. This is due to the predominance of the influence of the vagus nerve and the local irritant effect, which manifests itself with prolonged use of the drug.
Reserpine reduces body temperature, which is explained, apparently, by a decrease in the content of serotonin 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 sex glands in animals.
Preparations of this group are used as sedatives and antihypertensives for stress and other neuropsychiatric disorders, hypertension, mild forms of heart failure, thyrotoxicosis.
Side effects usually occur with prolonged use of drugs and are manifested by drowsiness, diarrhea, increased blood clotting, bradycardia, fluid retention in the body. These phenomena are removed by atropine.
Reserpine. The ester breaks down in the body into reserpic acid, which is an indole derivative, and other compounds. White or yellowish fine-crystalline powder, very slightly soluble in water and alcohol, well - in chloroform. The most active drug has a more pronounced local irritant effect.
Cattle are very sensitive to it, therefore, when administered intravenously, the dose should not exceed 7 mg per animal. Horses are also sensitive to reserpine, with a parenteral dose of 5 mg causing severe colic. Dogs and cats tolerate higher doses of reserpine - 0.03-0.035 mg/kg of body weight.
Used for prevention, treatment of stress, neurosis, hypertension, thyrotoxicosis. Contraindicated in severe cardiovascular diseases, insufficient kidney function, peptic ulcer of the stomach and duodenum,
Carbidine. An indole derivative. White crystalline powder, easily soluble in water, very little in alcohol; pH of solutions 2.0-2.5. It has neuroleptic, antipsychotic activity and moderate antidepressant action. Side effects are possible: stiffness, tremor, hyperkinesis, which can be removed with cyclodol.
It is used for nervous disorders, it is possible for the prevention of stress, in medicine for schizophrenia and alcoholic psychosis. Contraindicated in violation of liver function, drug poisoning and analgesics.
Lithium salts.
Lithium is an element from the group of alkali metals, widely distributed in nature, found in small amounts 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 1950s, lithium preparations were found to have a sedative effect on mental patients and prevent schizophrenic attacks. In this regard, lithium preparations belong to a new group of substances with a calming effect - normotimics. They are able to normalize the functions of the central nervous system and are active in both depression and excitation.
Pharmacodynamics of drugs is simple. They are rapidly absorbed after oral administration, distributed depending on the blood supply to organs and tissues. In the body, they dissociate into ions, which can be found in various organs and tissues 2-3 hours after the administration of the drug. Lithium is excreted mainly by the kidneys, and excretion depends on the content of sodium and potassium ions in the blood. With a lack of sodium chloride, lithium is retained, 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 nerve and muscle cells, and lithium is a sodium antagonist. According to the second, lithium increases the intracellular deamination of norepinephrine, reducing its content in the brain tissues. In large doses, it lowers the amount of serotonin. In addition, the sensitivity of the brain to mediators changes. The effect of lithium on healthy and sick people is not the same, so there are conflicting reports in the literature.
The pharmacodynamics of lithium has been studied in laboratory animals and in humans.
Compared with chlorpromazine, lithium affects the nervous system in a milder and longer, but weaker way. Lithium does not increase the threshold of sensitivity and does not suppress the defensive reflex, it reduces motor activity and research activity. Lithium oxybutyrate 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 excitatory effect on the central nervous system of various stimulants and at the same time weaken depression.
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