4. Analgesics CHARITABLE (ANALGEZING) MEANS

The cause of acute and chronic pain can be both organic and psychogenic disorders. Eliminating or relieving pain with analgesics improves the patient’s physical and mental well-being, which has a positive effect on his professional and social life.

Pain sensations are perceived by special receptors, which are called "nociceptors". The damaging (nociceptive) irritants can be mechanical, thermal and chemical effects. The cause of pain is often a pathological process (for example, inflammation). Endogenous substances are known that, acting on nociceptors, can cause pain (bradykinin, histamine, serotonin, potassium ions, etc.), Prostaglandins (for example, E) increase the sensitivity of nociceptors to chemical (and thermal) stimulation.

The presence of a significant number of different endogenous peptides, including those with analgesic activity (enkephalins,? -Endorphin, dinorphins, endomorphins), as well as algeticheskimi properties (for example, substance P). The latter cause or increase pain. Many other biologically active substances are also formed in the brain tissues, which can play the role of not only mediators, but also modulators of pain stimuli transmission. Peptides with analgesic activity (opioids) interact with specific opioid receptors, which are found in most of the formations involved in the conduction and perception of pain.

Thus, in the body there is a complex neurohumoral antinociceptive system. In case of its insufficiency (in case of excessively pronounced or prolonged damaging effects), pain sensations must be suppressed with the help of painkillers.

Analgesics are drugs that, by resorptive action, selectively suppress pain sensitivity. They do not turn off the mind and do not inhibit other types of sensitivity. Based on the pharmacodynamics of the respective drugs, they are divided into the following groups.

I. Means mainly central action

A. Opioid (narcotic) analgesics

1. Agonists

2. Antagonist agonists and partial agonists

B. Non-opioid drugs with analgesic activity

1. Non-opioid (non-narcotic) analgesics (derived from the pairs

butphenol)

2. Preparations from various pharmacological groups with analgesic

action component

Ii. Predominantly peripheral agents

Non-opioid (non-narcotic) analgesics (derivatives of salicylic acid, pyrazolone, etc.).

OPIOID (NARCOTIC) ANALGETICS AND THEIR ANTAGONISTS

The effects of opioid analgesics and their antagonists are due to the interaction with opioid receptors, which are found both in the central nervous system and in peripheral tissues.

They can be presented in the form of the following groups.

Agonists : Morphine Promedol Fentanyl Sufentanil

Antagonist agonists and partial agonists : Pentazocine Nalbuphine Butorphanol Buprenorphine

Many opioid analgesics belong to the first group of substances. Due to the fact that these analgesics interact with opioid receptors, they are called opioids.

Opioid analgesics have a pronounced inhibitory effect on the central nervous system. It manifests analgesic, hypnotic, antitussive action. In addition, most of them change mood (euphoria occurs) and cause drug dependence (mental and physical).

The group of opioid analgesics includes a number of drugs derived both from plant materials, and synthetically.

The most widely used in medical practice is alkaloid morphine. It is isolated from opium, which is a frozen milky juice, flowing from the poppy head cuts - Papaver sopiferit . In opium intended for medical purposes, should be not less than 10% morphine. Total opium contains more than 20 alkaloids. Some opium alkaloids are derived from phenanthrene, others are derived from isoquinoline.

For phenanthrene derivatives (morphine, codeine, and others), the inhibitory effect on the central nervous system (analgesic, antitussive) is mainly characteristic, and isoquinoline alkaloids (papaverine, etc.) have a direct spasmolytic effect on smooth muscles.

The main effect for morphine is the analgesic effect. Morphine has a selective analgesic effect. Other types of sensitivity in therapeutic doses, it does not suppress.

The mechanism of the analgesic effect of morphine is not fully elucidated. It is assumed that it consists of the following main components: 1) inhibition of the process of interneuronal transmission of pain impulses in the central part of the afferent path and 2) disturbances in the subjective-emotional perception, assessment of pain and reaction to it.

The mechanism of the analgesic effect of morphine is due to its interaction with opioid receptors. Stimulation of morpine opioid receptors is manifested by the activation of the endogenous antinociceptive system and the disruption of the interneuronal transmission of pain stimuli at different levels of the central nervous system. Thus, the direct inhibitory effect of morphine on spinal neurons is essential.

The calming effect of morphine may be due to its effect on the neurons of the cerebral cortex, on the activating ascending reticular formation of the brain stem, as well as on the limbic system and the hypothalamus.

One of the typical manifestations of morphine psychotropic action is the state of euphoria caused by it , which consists in an elevated mood, a sense of spiritual comfort, a positive perception of the environment and life prospects, regardless of reality.

Especially pronounced euphoria with repeated use of morphine. However, some people have the opposite effect: feeling unwell, negative emotions (dysphoria).

At therapeutic doses, morphine causes drowsiness. One of the manifestations of the central action of morphine is a decrease in body temperature. However, a distinct hypothermia is observed only with the introduction of large doses of morphine. Observed with the introduction of morphine (especially in toxic doses) constriction of the pupils (miosis) is associated with the excitation of the centers of the oculomotor nerve.

Morphine (starting with therapeutic doses) inhibits the center of respiration, reducing its excitability to carbon dioxide and reflex effects. First comes the reduction of respiratory rate, which is compensated by an increase in their amplitude. With increasing doses to subtoxic respiratory rhythm decreases even more, the amplitude of single breaths and minute volume fall. When morphine poisoning death occurs from paralysis of the respiratory center.

Morphine inhibits the cough reflex and has pronounced antitussive activity.

Morphine is usually depressing to the emetic center. However, in some cases it can cause nausea and vomiting. The center of the vagus nerve stimulates morphine, especially in large doses. Bradycardia occurs. Spinal reflexes with the introduction of morphine in therapeutic doses usually do not change, in large doses they are inhibited.

Morphine is not absorbed well enough from the gastrointestinal tract. Much of it is inactivated in the liver. For a more rapid and pronounced effect, the drug is usually administered parenterally. The duration of the analgesic action of morphine is 4-6 hours.

Through the blood-brain barrier, morphine penetrates poorly.

Omnopone (pantopon), which is a mixture of hydrochlorides of 5 opium alkaloids, is sometimes used as one of the substitutes for morphine.

In medical practice, many synthetic and semi-synthetic drugs have been used. Of considerable interest are piperidine derivatives. By analgesic activity, it is inferior to morphine by 2-4 times. Duration of action of Z-4 h. Causes nausea and vomiting less often than morphine. Slightly less depressing respiratory center. The tone of the smooth muscle organs reduces (ureters, bronchi) or increases (intestines, biliary tract), but is inferior to the spasmogenic effect of morphine. In a small degree enhances the contractile activity of the myometrium. From the gastrointestinal tract is absorbed well.

NARCOTIC SUBSTANCES: OPIOIDS.

1. Pharmacology of opioids.

2. Classification.

3. Acute opioid poisoning (overdose). Clinic.

4. Treatment of acute poisoning (overdose).

5. "The withdrawal syndrome" or withdrawal syndrome. Treatment.

Pharmacology.

The pharmacological effects of morphine and other opioids are associated with a similar structure, i.e. to similar natural opiate peptides: endorphins, enkephalins, dimorphins and some other peptides. All opioid receptors and their subtypes are classified as mu, kappa and delta. Mu receptors at the supraspinal level and kappa receptors at the spinal level are responsible for analgesia.

The standard agonist, Morphine, has pronounced activity against the mu receptors and moderate activity against the kappa and delta receptors. The agonist / antagonist model is Nalorphin. It exhibits an agonist action (agonist) of kappa receptors and a mu receptor antagonist Naloxon, an antagonist of all receptors.

An interesting mechanism based on the theory of opioid receptors may explain the phenomenon of tolerance and the withdrawal syndrome (withdrawal). Frequent use of opioid agonists may disrupt the number or configuration of receptors, or else it may reduce the regulation of the secretion of endogenous opioid peptides. As production of opioid peptides and secretion are reduced, more exogenous opioids are required, i.e. high dose tolerance occurs without any side effects such as sedation or respiratory depression. The sudden elimination of opioid use does not allow time to recover adequately functioning endogenous opioid production. As a result, permeability to sodium increases, followed by an increase in excitability and symptomatology of the "syndrome of withdrawal" (abstinence). Frequent and regular use of opioids leads to addiction. Physical dependence on opioids is believed to occur when:

1. To achieve the same effect, higher and higher doses are required.

There is a behavioral need for buying and using drugs.

There is a dependency caused by "withdrawal syndrome" or cessation of drug use.

The level or degree (rate) of opioid metabolism does not increase over time, as is the case with ethanol and barbiturates. The biological half-life of heroin is exceptionally short:

Diacetylmorphine (heroin) is converted to the biologically active 6-mono-acetylmorphine (6-MM) in the liver, brain, kidneys and heart; then 6-MM slowly turns into morphine in these organs.

Morphine conjugates with glucuronic acid or excreted unchanged.

Morphine - 6 - beta-glucuronide, an active metabolite of morphine with an activity greater than 100 times the activity of morphine and having a slightly longer half-life.

CLASSIFICATION

AGONISTS:

1. Natural Opium Derivatives. Morphine Codeine

2. Semisynthetic. - Heroin-Hydromorphone-Oxymorphone-Oxycodone

3. Synthetic. Meperidine-Methadone-Fentanyl-Propoxyphene-Diphenoxylate

AGONISTS / ANTAGONISTS

-Buprenorphine-Nalorfin-Pentazocine-Nalbuphine

Antagonists

-Naloxon-Naltrexone

Complications of opioid addiction

1.SSN: bacterial endocarditis, thrombophlebitis, pseudoaneurysms, vasculitis

2. CNS: epidural abscesses, post-toxic (after respiratory depression and oxygen insufficiency) encephalopathy, paraplegia, parkinsonism.

3. Pulmonary: bronchospasm, pulmonary edema, aspiration pneumonitis, septic pulmonary embolism, granulomatosis, "pulmonary heart", abscesses, empyema.

Systemic infections: tetanus, hepatitis, malaria, tuberculosis, AIDS.

Skeletal muscles: "crash" - a syndrome, a syndrome of prolonged pressure,

rhabdomyolysis, osteomyelitis, septic arthritis.

6. Dermatological, endocrine, gastrointestinal, genito-urinary and other complications.

TREATMENT OF ACUTE OPIOID POISONING

1. Basic stabilization:

Dextrose 50% -100 ml

Thiamine (B ₁ ) 100 ml (1% - 10 ml)

Antidote "Naloxone" 2 mg IV initial dosage.

A single injection of Naloxone has a duration of action from 20 to 60 minutes. Since the duration of action of most opioids is longer than the duration of action of naloxone, patients should receive repeated doses of Naloxone, or a constant maintenance dosage should be administered to prevent a repeated episode of respiratory depression.

Patients who have had an episode of respiratory failure should be taken to hospital and monitored for 12-24 hours.

Opioid withdrawal symptoms (Withdrawal Syndrome)

symptoms:

1. Neurologically: agitation, hyperactivity, anxiety, craving for drugs, convulsions in newborns (if the mother used opiates).

2. Cardiovascular: hypertension, tachycardia.

3. Respiratory: tachypnea

4. Gastrointestinal tract: nausea, vomiting, abdominal cramping, diarrhea.

5. Others: mydriasis, yawning, lacrimation, rhinorrhea, tremor, sweating, piloerection (contraction of the muscles lifting the hair), muscle pain and spasm.

TREATMENT OF OPIOID CANCELING SYNDROME

1. Methadone.

The effectiveness of methadone is associated with its ability to block the euphoric effect of other opioids and the ability to prevent the development of "withdrawal syndrome". Methadone can be given orally (tablet form) once a day, because It has a half-life of 24-36 hours.

The treatment lasts for several years (2-3 years). The dose of methadone produced is gradually reduced by 10-20% daily. If withdrawal symptoms reappear, the dosage is reduced more slowly.

2. Clophelin (Clonidine).

Clophelin is effective in opioid withdrawal, since It stimulates alpha adrenergic receptors in the brain.

3. Naltrexone.

This is a long-acting drug. Naltrexone can be administered once a day or three times a week and effectively suppresses any euphoric effect of opioids.

MARIJUANA

Cannabis sativa (cannabis sativa) or marijuana is one of the oldest cultivated plants. Used cellulose plant stems and flowering tip.

There are several marijuana derivatives:

- ,, grass ,, or marijuana itself.

Smoking form in the form of cigarettes. ,, Hashish ,, - dried marijuana resin with a THC content of 10%. Smoked in pipes or added to food or simply swallowed by drug addicts.

Hashish oil with a THC content of up to 50%.

PHARMACOLOGY.

The main “target” is the brain, where it interacts with specific receptors, the maximum number of which is located in the cerebral cortex (frontal divisions), the limbic system, the hippocampus and the cerebellum. A direct correlation was established between behavioral disorders and THC distribution in the brain.

The main effect of THC on the brain is “pleasant,” that is, subjectively elevating mood, which may be the result of stimulation of the limbic system.

Euphoria is associated with a subjective feeling of a change in cognition, the appearance of changeable (wandering) sensations, perceptual changes in hearing, vision, tactile sensations and depersonalization. A similar condition lasts 3-4 hours after one cigarette. The negative impact of marijuana on memory includes disintegration (decay) of a short memory (ie memory for recently acquired knowledge and events). The effect of low concentrations of THC includes euphoria, passivity, a period of subjective knowledge and skills, and disorientation in what is happening.

The whole range of symptoms associated with marijuana includes:

- Mental:

- a feeling of separation from the body, the absence of any thoughts, euphoria, relaxation, a sense of complete well-being, daydreaming, cheerfulness, ridiculousness, a rapid change in mood.

- thinking process: thoughts that are irrelevant, violations of associative thinking, reduced concentration, disorientation.

- novelty of sensory sensations, liveliness of emerging images (auditory and visual).

- violation of the perception of time and space, changing the perception of the outlines of his own body, damage to sexual sensations.

- difficult to adapt to the environment effects of behavior: violation of critical judgments, difficulties in performing social and professional functions, insufficient sense of responsibility.

- Change of speech: incoherent, fast, devoid of meaning.

- Bad ,, short ,, memory (for recently received information, knowledge, events,).

- Fear of death.

Physical:

- Feelings of severe heart attack and chest tightness.

- The severity and pressure in the head.

- Increased appetite and thirst, nausea, dizziness, paresthesias, somnolentia, anxiety, ataxia, thermor, dry mouth, tachycardia, injected conjunctiva of the eyes.

Other effects:

-THC and other selective cannabinoids inhibit macromolecular synthesis of DNA and RNA, as well as the same proteins, leading to the inhibition of cellular immunity, macrophage function and delayed fetal development.

- Cannabis extract and smoking condensate have potential mutagenic and carcinogenic risks.

THC взаимодействует как с медикаментами, так и с другими наркотическими веществами.

Так, THC усиливает эффект веществ, угнетающих ЦНС: алкоголя, седативных препаратов, гипнотиков, опиоидов.

,,Синдром отмены,, (или абстиненции) протекает так-же, как при отмене седативных препаратов или опиоидов, включая беспокойство, нарушения сна, тошноту, дисфорию.

В процессе курения многие химические компоненты разрушаются под воздействием температуры и вырабатываются новые химические продукты, в зависимости от температуры горения сигареты, pH растительного сырья, его влажности, размера частиц и химического состава растения.

Все эти химические компоненты и варианты определяют конечный эффект выкуриваемой сигареты с марихуаной на организм.

THC is rapidly absorbed and distributed, mainly in adipose tissue (neutral fat, liver, lungs, spleen). In general, the volume of distribution ranges from 500 to 2000 L.

Less than 1% reaches the brain. In order to disrupt the normal functioning of the CNS cells and organ function, a very small amount of THC is required, measured in nanomoles and micromoles.

Cannabinoids cross the placental barrier and are found in breast milk.

The elimination half-life of THC is approximately one week. Approximately one month is required for complete elimination, with 80% excreted through bile - 20% through urine. TREATMENT.

There is no specific medical treatment for marijuana intoxication.

THC-induced psychoses are usually short-lived and pass spontaneously over time.

Patients with THC intoxication are rarely aggressive. If necessary, sedative-hypnotics are administered, such as, Diazepam, (Seduxen) 5–20 mg IV.

Chronically cannabis users are difficult to treat, because their categorical denial of the use of cannabis is progressing, and the negative effects are very difficult to detect.

Amphetamines

Pharmacology.

Amphetamines belong to the phenylethylamine family.

1) Amphetamines increase secretion and block the reuptake of catecholamines, and in addition, they have some other actions on catecholamine receptors. As a result, both alpha and beta adrenergic receptors are stimulated.

2) In large doses, amphetamines can cause the release of 5-hydroxytryptamine (serotonin) and disrupt the function of serotonin receptors.

3) Amphetamines can also inhibit the activity of monoamine oxidase.

Эффекты серотонина и допамина на мезолимбическую систему нарушают перцепцию (восприятие окружающего мира) и вызывают различные психозы.

Период полураспада амфетаминов варьирует от 8 до 30 часов.

КЛИНИЧЕСКИЕ ЭФФЕКТЫ АМФЕТАМИНОВ .

Клинические эффекты амфетаминов связаны со стимуляцией центральных и периферических адренергических рецепторов. Эти клинические проявления аналогичны Кокаину и могут практически не отличатся от них, за исключением времени длительности действия (Амфетамины- до 24 часов).

Острые отравления Амфетаминами.

ССС :

-Гипертензия-Тахикардия-Нарушения сердечниго ритма (дизритмия)- Вазоспазм (коронарный и периферический)- Ишемия миокарда- Кардиомиопатия

ЦНС:

- Возбуждение - Судороги- Гипертермия- Головная боль- Эйфория- Анорексия- Внутречерпные кровоизлияния или инфаркты- Хореоатетозные движения- Гиперрефлексия- Параноидальный психоз

Другие симптомы, связанные со стимуляцией ЦНС:

- Потливость- Тахипноэ- Мидриаз- Тремор- Тошнота

Другие органы и системы :

- Напряжение скелетной мускулатуры- Рабдомиолиз- Отёк лёгких

Психомоторное возбуждение, гипертермия, напряжение скелетной мускулатуры, судороги могут привести к рабдомиолизу, острому тубулярному некрозу и коагулопатии.

Смерть от Амфетаминов может наступить в результате нарушения сердечного ритма, гипертермии, внутричерепного кровоизлияния.

ХРОНИЧЕСКАЯ АМФЕТАМИНОВАЯ ИНТОКСИКАЦИЯ

- Некротические васкулиты- Кардиомиопатия- ИБС- Панкреатиты, почечная недостаточность- Инфекции: СПИД, гепатиты, эндокардиты, столбняк, остеомиелиты, абсцессы

Лабораторные данные :

- Лейкоцитоз- Гипергликемия- Повышение аминотрансфераз- Миоглобинурия

КОКАИН

Кокаин- естественный алкалоид, содержащийся в листьях растения Erytroxylon coca. Это кустарник, обильно произростающий в Колумбии, Перу, Боливии, Мексике. Западной Индии и Индонезии.

ФАРМАКОЛОГИЯ.

Фармакологические эффекты Кокаина включают:

- Увеличение синтеза, высвобождения и обратного захвата норадреналина

,,Кокаиновая лихорадка,, может быть вызвана следующими причинами:

1) Увеличением психомоторний активности и кокаин-индуцированной теплопродукцией (увеличением продукции тепла).

2) Уменьшением теплоотдачи в результате кокаин-индуцированного спазма сосудов.

3) Direct pyrogenic effect on thermoregulation centers in the hypothalamic region.

The onset of action of cocaine depends on the dose and the route of entry into the body:

- by inhalation after 1-3 minutes.

- in / in and when smoking: after a few seconds and the peak of action in 3-5 minutes.

- with topical application to the nasal mucosa: after a few minutes and the peak of action after 20-30 minutes.

- at admission through the gastrointestinal tract: 60-90 minutes.

Cocaine is rapidly metabolized in the liver and is mainly excreted in the urine (approximately 80%) within 24 hours.

The lethal dose of Cocaine at admission through the gastrointestinal tract is 500 mg.

,, The classic ,, lethal dose is 1 gram, but deaths are also described when ingesting 20 mg intranasally.

При хроническом употреблении Кокаина развивается толерантность и кокаин-наркоманы употребляют до 10 грамм в сутки без каких-либо серьёзных острых токсических реакций.

КЛИНИЧЕСКИЕ ЭФФЕКТЫ КОКАИНА

ССС:

-Тахикардия или брадикардия, гипертензия, нарушения сердечного ритма, спазм коронарных сосудов, ИБС, инфаркт миокарда, разрыв аорты.

ЦНС:

- Возбуждение, судороги, галлюцинации, тремор, психоз, паранойя, беспокойство, затемнение сознания, головная боль,, внутричерепное кровоизлияние, инфаркты головного мозга, двигательные нарушения, гипертермия.

Костно-мышечная система:

- Инфаркты в мышцы, рабдомиолиз, миоглобинурия

Венозная система:

- Васкулиты, тромбофлебиты

Дыхательная система:

-Быстрые и нерегулярные дыхательные движения, хронические заболевания лёгких, отёк лёгких.

Метаболические:

-Лактоацидоз, потеря веса.

Others:

- Мидриаз, вертикальный и горизонтальный нистагм, кератопатия, слепота.

- Анорексия, тошнота. диарея, боли в животе, тромбозы мезентериальных сосудов, перфорация кишечной стенки.

- Васкулиты сосудов почек, инфаркты почек, тубулярный некроз.

- Изъязвление кожи и слизистых на месте топического применения Кокаина.

ЛЕЧЕНИЕ ПАЦИЕНТОВ С КОКАИНОВОЙ И АМФЕТАМИНОВОЙ ИНТОКСИКАЦИЕЙ.

- Обеспечение нормального функционирования жизненно-важных органов и систем.

one). Оксигенация.

2). Лечение гипертензии: антагонисты альфа-адренергических рецепторов (Фентоламин) или сосудорасширяющие средства (Нифедипин или Нитропруссид)

3). 100 мл 50% Глюкозы в/в, 100 мг Тиамина в/в

four). Гипертермия: физические методы охлаждения.

five). Возбуждение, делирий, судороги: седация бензодиазепинами или введение миорелаксантов и ИВЛ

6). Нейролептики (Галоперидол) рекомендуются для амфетамин-индуцированного делирия без нарушения жизненноважных функций.

Пациентыс ОПН, ацидозом и гиперкалиемией требуют проведения гемодиализа.

НЕОПИОИДНЫЕ ПРЕПАРАТЫ ЦЕНТРАЛЬНОГО ДЕЙСТВИЯ С АНАЛЬГЕТИЧЕСКОЙ АКТИВНОСТЬЮ

Интерес к неопиоидным анальгетикам в основном связан с поиском эффективныx болеутоляющих средств, не вызывающих наркоманию.

НЕОПИОИДНЫЕ (НЕНАРКОТИЧЕСКИЕ) АНАПЬRЕТИКИ ЦЕНТРАЛЬНОГО ДЕЙСТВИЯ. (ПРОИЗВОДНЫЕ ПАРААМИНОФЕНОПА)

Производное парааминофенола - парацетамол - как неопиоидный анальгетик центрального действия.

Парацетамол (ацетаминофен, панадол, тайленол, эффералган), являющийся активным метаболитом фенацетина, широко используется в медицинской практике.

It is characterized by analgesic and antipyretic effects. The mechanism of action is associated with its inhibitory effect on cyclooxygenase, which leads to a decrease in the synthesis of prostaglandins in the CNS. At the same time, in the peripheral tissues, the synthesis of prostaglandins is practically not disturbed, which explains the lack of anti-inflammatory action in the preparation. In terms of effectiveness, paracetamol roughly corresponds to acetylsalicylic acid (aspirin). Quickly and completely absorbed from the digestive tract. The maximum plasma concentration is determined in 30-60 minutes. t _1/2 = 1-3 hours. It binds to plasma proteins to a small extent. Metabolized in the liver. The resulting conjugates (glucuronides and sulfates) and unchanged paracetamol are excreted by the kidneys.

Apply the drug for headache, myalgia, neuralgia, arthralgia, with pain in the postoperative period, with pain caused by malignant tumors, to reduce the temperature during fever. He is well tolerated. In therapeutic doses, rarely causes side effects. Allergic skin reactions are possible. Unlike acetylsalicylic acid, it does not have a damaging effect on the gastric mucosa and does not affect platelet aggregation. The main disadvantage of paracetamol is its small therapeutic breadth. Toxic doses exceed the maximum therapeutic all 2-3 times. In acute poisoning with paracetamol, serious damage to the liver and kidneys is possible. They are associated with the accumulation of toxic metabolites - N-acetyl-p-benzoquinoneimine. This results in necrosis of the liver cells and the renal tubules (24-48 hours after poisoning). Treatment of acute paracetamol poisoning includes gastric lavage, the use of activated carbon, as well as the introduction of acetylcysteine ​​(increases the formation of glutathione in the liver) and methionine (stimulates the conjugation process). The introduction of acetylcysteine ​​and methionine is effective in the first 12 hours after poisoning, until irreversible changes in the cells occur.

Paracetamol is widely used in pediatric practice as an analgesic and antipyretic agent. Its relative safety for children under 12 years of age is due to their inadequate cytochrome P-450 system, and therefore the sulfate pathway of paracetamol biotransformation prevails. At the same time toxic metabolites are not formed.

PREPARATIONS VARIOUS PHARMACOLOGICAL GROUPS WITH ANALGETIC COMPONENT OF ACTION

Representatives of different groups of non-opioid substances may have quite pronounced analgesic activity. One of these drugs is (X2-adrenomimetic clonidine, used as an antihypertensive agent. In animal experiments, it was shown that it is superior to morphine in analgesic activity. with the participation of α ₂ -adrenoreceptors. The drug inhibits the reaction to pain from hemodynamics. Breathing does not inhibit. Drug dependence does not cause.

Clinical observations confirmed the pronounced analgesic efficacy of clopheline (for myocardial infarction, in the postoperative period, for pain associated with tumors, etc.). The use of clonidine is limited by its sedative and hypotensive properties. Enter usually under the shell of the spinal cord.

Analgesic activity is also expressed in tricyclic antidepressants amitriptyline and imizine. Obviously, the mechanism of their analgesic action is associated with inhibition of neuronal seizure of serotonin and norepinephrine in the descending paths that control the conduction of nociceptive stimuli in the posterior horns of the spinal cord. Effective mainly for chronic pain. However, in combination with certain antipsychotics (for example, fluorophenazine), they are also used for severe pain associated with postherpetic neuralgia, and for phantom pain.

The analgesic effect is characteristic of nitrous oxide used for inhalation anesthesia. The effect manifests itself in sub-drug concentrationsx and can be used to relieve severe pain for several hours.

A pronounced analgesic effect causes a phencyclidine ketamine derivative, used for general anesthesia (for the so-called dissociative anesthesia). It is a noncompetitive glutamate NMDA receptor antagonist.

Separate anti-histamine agents that block histamine H1 receptors also have analgesic properties (for example, Dimedrol). It is possible that the histaminergic system is involved in the central regulation of pain conduction and perception. However, a number of anti-histamine drugs have a wider range of action and may affect other pain mediators / modulators systems.

The group of antiepileptic drugs that block sodium channels, such as carbamazepine, sodium valproate, diphenin, lamotrigine, gabapeptin, etc., also has analgesic activity. It is used in chronic pain.

An analgesic effect has also been found in some GABA receptor agonists (baclofen 1, THIp ₂ ).

Analgesic properties are also noted in somatostatin and calcitonin.

ANALGETICS WITH A MIXED MECHANISM OF ACTION (OPIOID + NEOPIOID)

This group of substances includes tramadol (tramal). It interacts with opioid receptors, and also affects the monoaminergic system involved in the regulation of pain stimuli. The affinity for opioid receptors is significantly less than that of morphine. The non-opioid component of analgesia is obviously associated with a decrease in the neuronal uptake of serotonin and norepinephrine. One of the manifestations of this effect is the enhancement of spinal inhibitory serotonergic and adrenergic effects on the interneuronal transmission of nociceptive impulses.

Tramadol is 5-10 times less active than morphine, however, by its analgesic efficacy when used in moderate therapeutic doses, it is comparable with opioid receptor agonists. Little effect on respiration and function of the digestive tract. It has a significantly lower narcogenic potential than opioid receptor agonists.

With intravenous administration, analgesia develops in 5-10 minutes, and with enteral administration - in 30-40 minutes. Duration of action 3-5 hours. Metabolized in the liver. The metabolite O-desmethyltramadol is 2-4 times more active than tramadol. Tramadol and its metabolites are excreted by the kidneys.

The drug is used for moderate to severe chronic and acute pain. Enter inside, rectally and intravenously 4 times a day.

Of the side effects are possible headache, dizziness, lethargy, reduced speed of motor reactions, increased sweating, hypotension: Ia, tachycardia, dry mouth, constipation, abdominal pain, skin rashes; When administered in large doses, seizures sometimes occur.

Tramadol's weak antidote is naloxone.