Attention! Information is for reference only!
Before taking the course, consult a doctor!
WEB SITE ONLY DIRECTORY. NOT PHARMACY! We do not sell medicines! None!

Analgesic agents

Analgesics, or analgesics (from the Greek algos - pain and an - without), are called drugs that have a specific ability to ease or eliminate the feeling of pain.
An analgesic (analgesic) effect can be exerted not only by analgesics proper, but also by other substances belonging to different pharmacological groups. So, the analgesic effect may have drugs used for anesthesia (general anesthesia), and some of them in appropriate concentrations and doses (for example, trichlorethylene, nitrous oxide) are used specifically for analgesia. Local anesthetics are essentially analgesic in nature. With pain associated with spasms of smooth muscles, analgesic and anticholinergic agents may have an analgesic effect.
Under analgesic (analgesic) in the proper sense of the word means means, the dominant effect of which is analgesia, which occurs as a result of resorptive action and is not accompanied in therapeutic doses by switching off consciousness and pronounced violation of motor functions.
By chemical nature, the nature and mechanisms of pharmacological activity, modern analgesics are divided into two main groups. A. Narcotic analgesics, including morphine and related alkaloids (opiates) and synthetic compounds with opioid-like properties (opioids). B. Non-narcotic analgesics, including synthetic derivatives of salicylic acid, pyrazolone, aniline and other compounds.
For narcotic analgesics, the following main features are characteristic.
1. Strong analgeziruyuschee activity, providing the possibility of their use as highly effective painkillers in various areas of medicine, especially in trauma (surgery, injuries, etc.) and in diseases accompanied by severe pain syndrome (malignant neoplasms, myocardial infarction, etc.) .
2. Special influence on the human CNS, manifested in the development of euphoria and the appearance of repeated use of syndromes of mental and physical dependence (drug addiction), which limits the possibility of long-term use of these drugs.
3. Development of a painful condition (withdrawal syndrome) in persons with developed syndrome of physical dependence when depriving them of their analgesic preparation.
4. The removal of acute toxic phenomena caused by them (respiratory depression, cardiac disorders, etc.), as well as the analgesic effect of specific antagonists (see Naloxone).
With the repeated use of narcotic analgesics, habituation (tolerance) usually develops, that is, a weakening of the effect, when increasing doses of the drug are required to obtain an analgesic effect.
The action of narcotic analgesics is not limited to analgesic effect. In one way or another, they have a hypnotic effect, depress respiration and cough reflex, increase the tone of the intestine and bladder, can cause nausea, vomiting, constipation and other side effects.
Due to the pronounced narcogenic potential (i.e., the ability to cause addiction with the addiction syndrome) and the significant shifts in the activity of the central nervous system and other body systems associated with it, all narcotic analgesics are subject to storage, prescription and dispensing from pharmacies according to special rules.
The severity of the analgesic effect and the side effects of different drugs of this group differ among themselves, which is due to the peculiarities of their chemical structure and physico-chemical properties and, accordingly, interaction with the receptors involved in the implementation of their pharmacological effects.
In recent years, a number of previously used narcotic analgesics with a pronounced narcogenic potential (tecodin, hydrocodone phosphate, phenadone, some ready-made dosage forms containing opium or codeine) have been excluded from the nomenclature of medicines.
At the same time, a number of new synthetic highly effective narcotic analgesics have been created.
By sources of reception and chemical structure, modern narcotic analgesics are divided into 3 groups: a) natural alkaloids - morphine and codeine, contained in the hypnotic poppy; B) semisynthetic compounds obtained by chemical modification of the morphine molecule (ethylmorphine, etc.); C) compounds formed as a result of complete chemical synthesis (promedol, fentanyl, pentazocine, nalbufin, butorphanol, tramadol, etc.). Most synthetic drugs are obtained by the principle of modifying a molecule of morphine with the preservation of elements of its structure or its simplification. This way a set of drugs has been obtained that differ in strength and duration of the analgesic effect, in the rapidity and degree of development of addiction, addiction and other side effects, in ability to inhibit the motor activity of the intestine and have an opposing effect (see Loperamide), antitussive effect, etc. Some Drugs have a smooth muscle spasmolytic effect (see Promedol).
By chemical modification of the morphine molecule, compounds that are its pharmacological antagonists have also been obtained (see Naloxone).
The mechanism of action of narcotic analgesics has not been sufficiently studied.
Neurophysiological studies indicate oppression of narcotic analgesics by thalamic centers of pain sensitivity and blocking the transmission of pain impulses to the cerebral cortex. This effect is, in all probability, leading in the physiological mechanism of action of analgesics of this group.
In the neurochemical aspect, it is important to study the effect of these substances on the neurotransmitter processes of the brain and peripheral organs. There are data on the inhibitory effect of morphine on the hydrolysis of acetylcholine and its isolation from nerve endings. It is established that morphine activates the biosynthesis of serotonin. However, reserpine, which reduces the content of serotonin in the brain, weakens the analgesic effect of morphine and its analogues.
In general, there is insufficient data on the role of this neurotransmitter in the mechanism of action of narcotic analgesics. Data on the role of adrenergic processes and the GABAergic system are also contradictory. Shifts in the GABA system under the influence of different opiates and similar substances are ambiguous.
Of particular importance for understanding the mechanism of action of opiates are recent data on the presence in the brain and other organs of specific <opiate> receptors. Endogenous ligands, i.e. Binding with these receptors specific, formed in the body by physiologically active compounds, are neuropeptides - enkephalins and endorphins. Enkephalins are pentapeptides containing five amino acid residues. The so-called met-enkephalin (methionine-enkephalin) has the structure: H-tyrosyl-glycyl-glycyl-phenylalanyl-methionyl-OH. Endorphins have a somewhat more complex structure. So,
-endorfin (one of the most active endorphins) consists of 31 amino acids. Enkephalins and endorphins, when linked to opiate receptors, have an analgesic effect, and their effect is blocked by specific opiate antagonists. The binding of morphine to these receptors is ensured by the fact that a certain part of its molecule has a structural and conformational resemblance to a part of molecules (tyrosine residue) of enkephalins and endorphins. Thus, the exogenous analgesic morphine (as well as other closely related opiates and opioids) when introduced into the body interacts with the same "binding sites" (receptors) that are designed to bind endogenous analgesic compounds - enkephalins and endorphins.
It is not excluded that the action of exogenous analgesics is also related to the stabilization of endogenous neuropeptides (enkephalins, etc.) by inactivation of enzyme enkephalin-enkephalinases.
It has now been established that endogenous ligands for opiate receptors are not only enkephalins and endorphins, but also other peptides (dinorphines, etc.). It is also shown that opiate receptors exist in the form of different subpopulations: (mi), (kappa), (delta), (sigma), which have different functional significance. It is believed that - the receptors mediate supraspinal analgesia, euphoria, respiratory depression and physical dependence; - receptors mediate spinal analgesia, miosis, sedation, etc. Different endogenous peptides and narcotic analgesics can bind predominantly to one or another subgroup of receptors, which can determine the characteristics of their pharmacological action.
Various narcotic analgesics differ also in the nature of binding to opiate receptors. Some of them (morphine, promedol, fentanyl, etc.) are "pure" (full) agonists; Binding to receptors, they have a characteristic physiological (pharmacological) action characteristic of endogenous ligands. Others are "pure" antagonists (see Naloxone). By binding to receptors, they block the action of endogenous ligands and exogenous opiates. The third group includes preparations of a mixed type of action (agonists-antagonists), differently associated with different subgroups of opiate receptors and, in this connection, exerting an agonistic effect on one type of action, antagonistic effect on others (nalorphine, pentazocine, nalbuphine, etc.). .
The action of narcotic analgesics on peripheral organs (intestines, etc.) is also associated with interaction with opiate receptors located in them.
There is no pronounced local anesthetic effect in most opiates. At the same time, in recent years, they have been found to exert a strong general analgesic effect in epidural and subarachnondal administration. This effect is associated with a direct effect on the neuronal systems of the spinal cord involved in the formation of a painful flow of impulses. This method of introducing opiates has recently become more and more used for the relief of severe acute and chronic pain.
Typical for non-narcotic analgesics are the following main features.
1. Analgesic activity, manifested in certain types of pain: mainly with neuralgic, muscle, articular pain, headache and toothache. With severe pain associated with injuries, cavitary surgery, etc., they are practically ineffective.
2. Antipyretic effect, manifested in febrile states, and anti-inflammatory effect, expressed in different degrees in different compounds of this group.
3. Absence of depressing influence on the respiratory and cough centers.
4. Absence in their application of euphoria and phenomena of mental and physical dependence.
The main representatives of non-narcotic analgesics are:
A) derivatives of salicylic acid (salicylates) - sodium salicylate, acetylsalicylic acid, salicylamide, etc .;
B) derivatives of pyrazolone - antipyrine, amidopyrine, analgin;
C) derivatives of para-aminophenol (or aniline) - phenacetin, paracetamol.
In the mechanism of action of non-narcotic analgesics, a certain role is played by the influence on thalamic centers, which leads to inhibition of pain impulses to the cortex. According to the central effect, these analgesics differ, however, from narcotic analgesics by a number of features (for example, they do not affect the ability of the central nervous system to sum up subthreshold pulses).
In the mechanism of action of salicylates, the inhibition of the biosynthesis of prostaglandins plays an important role (see Acetylsalicylic Acid), as well as the stimulating effect on the <axis> of the pituitary gland - the adrenal gland, which promotes the release of corticosteroids. Significant importance in the action of non-narcotic analgesics has their influence on the kinin system (antagonism with the bradykinin's algebraizing action, etc.).

Subgroup Analgesics include preparations: