Antipyretica

Antipyretica (antipyretics), medicinal substances that cause a lowering of body temperature. A variety of medicinal substances can cause an antipyretic effect, for example, narcotics of the fatty series in sufficient doses, certain alkaloids, and others. However, these substances do not belong to the class of proper antipyretics, because their antipyretic action is a secondary factor. Substances belonging to class A. are medicinal agents which, even in therapeutic doses, selectively act on the thermoregulatory centers and cause a decrease in elevated body temperature without sharply disturbing other bodily functions. Unfortunately, the A. proposed so far are not ideal. - Body temperature is balanced by two physiological processes—heat production within the body on one hand, and heat loss to the external environment on the other. Consequently, the antipyretic effect may be caused either by increased heat loss, or decreased heat production, or by a combined action of both these factors. Proceeding from this premise, modern A. can be divided into two main groups. Representatives of the first cause a decrease in high temperature due to increased heat loss to the external environment, representatives of the other lower temperature, mainly due to weakening of heat-producing processes within the body. A., which increase heat loss, include the following antipyretics: antipyrine and its derivatives, aniline derivatives, para-aminophenol and quinoline derivatives, and the salicylic acid group. Representatives of these groups are very diverse, since the chemistry of carbon compounds allows—by replacing or attaching various organic complexes and radicals—the formation of a whole series of similar compounds. Side chains naturally have a certain influence on the pharmacotherapeutic action of the A. core, but in essence the characteristic of each group remains constant. For example, by replacing in para-aminophenol the hydrogen of the hydroxyl with various alcohol residues, and the hydrogen of the amide with this or that acid radical, one can obtain a very long series of homogeneous compounds. Their medicinal difference will only be in details. Thus, a para-aminophenol derivative—lactophenyl, which differs from phenacetin in that instead of the acetic acid radical, the residue of lactic acid is introduced—acts similarly to phenacetin but possesses more strongly expressed sedative and hypnotic properties, since lactic acid has certain independent properties and leaves a certain imprint on the overall pharmacotherapeutic action of the drug. There is no fundamental difference in the antipyretic action of representatives of all the above-mentioned groups of A.: all of them calm the thermoregulatory centers excited by pyrogenic substances and cause dilation of the skin vessels. As a result, there is an increased flow of blood into the skin vessels and increased dissipation of heat into the external environment. In this case, profuse sweating, which promotes more intensive heat loss, also has a certain significance. Heat loss in febrile animals increases by 55% (Gottlieb). At the same time, no noticeable decrease in heat production is observed. On the contrary, there are even indications of an intensification of heat-producing processes under the influence, for example, of antipyrine or salicylic acid; however, the increase in heat production is significantly inferior to the increased heat loss, and therefore in the final analysis temperature falls. - Among the best and most frequently used A. are substances of the antipyrine group. Their action is rapid, toxic phenomena at therapeutic doses are observed comparatively rarely, the subsequent rise in temperature occurs without a sharp, shaking chill, unfavorable effects on the heart and blood are not detected. Aniline derivatives (antifebrin) possess strong antipyretic action and are even more energetic than antipyrine, but are used less frequently in therapy because aniline is a blood poison that destroys red blood corpuscles and converts the blood's Hb into methemoglobin. This property extends to a certain degree to aniline derivatives as well: after taking antifebrin, cyanosis, methemoglobinemia are sometimes observed, and with prolonged use, marked weakness and anemia characteristic of chronic aniline poisoning and the so-called aniline cachexia may appear. In addition, the use of antifebrin is more often accompanied than with antipyrine by profuse, distressing sweating at the fall in temperature and a more pronounced chill at the new rise. Collapse is also frequently observed. - Although para-aminophenol is chemically related to aniline, representing its para-oxy derivative, nevertheless, derivatives of para-aminophenol (phenacetin, etc.) possess significantly less toxic properties than aniline derivatives. Temperature falls rapidly (after 1/2-1 hour) and, for the most part, without sharp side effects. The rise in temperature is gradual; the poisonous influence on the blood is slight; therefore, para-aminophenol derivatives belong to the best A. - Salicylic preparations produce a strong and rapid antipyretic effect, but more sharply disturb cardiac function and cause side effects. Quinoline derivatives (thalii, kairin) are no longer used. A., which decrease heat production, include preparations of quinine and its derivatives. Quinine is a protoplasmic poison, which in sufficient concentration acts detrimentally on oxidative and enzymatic processes, therefore the decrease in heat production after it is quite understandable. Quinine has a relatively slow antipyretic action, more varied and toxic influence on the organism in general and on the cardiac muscle in particular than other A. (antipyrine, phenacetin) and therefore is less frequently used for the purpose of lowering temperature. In addition to the antipyretics listed, there are others representing chemical combinations of some of those named, for example, salipyrine—a combination of salicylic acid and antipyrine, saloquine—a combination of quinine and salicylic acid, etc. Their action is understandable from the chemical composition. On the temperature of a healthy person or animal, A. exert a very weak influence. This occurs because normally functioning thermoregulatory centers cope with the narcotic influence which A. exert on them. But centers excited by an infectious agent or other pyrogenic substance cannot fully resist the strong action of A., and temperature is lowered. It falls within 1-5 hours, remains for several hours at low levels, and then begins to rise slowly again. Diseases with intermittent or remittent fever are more susceptible to the influence of A. than diseases associated with high temperature having the character of febris continua. A particularly strong antipyretic effect occurs in the case if A. are given before the critical fall in temperature: a synergism of physiological and medicinal antipyretic action occurs, which is very dangerous, and a sharp fall in temperature can easily cause weakening of cardiac function with severe collapse. - A. sometimes cause a number of other undesirable side effects. These include: the influence of A. on blood, cardiac function and the possibility of collapse, weakening of sweating, heavy, shaking chill, phenomena from the central nervous system (ringing in the ears, weakening of vision, dizziness, darkening of consciousness), nausea, vomiting, skin rashes. On blood, the most toxic action is exerted by substances of the aniline group; the least action is exerted by A. of the antipyrine group. On the cardiac muscle, quinine acts most strongly (but in small doses it stimulates the cardiac muscle—therapeutic action). Then come salicylic acid derivatives, and the least toxic influence is exerted by the antipyrine group; pyramidon, an antipyrine derivative, is even capable of stimulating the activity of an isolated heart, due to the presence of the amide group in pyramidon. - As a rule, during the antipyretic process, increased sweating appears, and at the reverse rise in temperature, chill is observed. The more gradual the fall in temperature, the longer the apyrexia, and the less pronounced the chill at the reverse rise in temperature, the more valuable the antipyretic agent. Here the antipyrine group should be placed first in qualitative terms; in last place are the now unused quinoline derivatives. After taking A., sometimes increased sensitivity to individual representatives of A. is observed, which sometimes reaches high degrees of idiosyncrasy. - A. are representatives of a class of medicinal substances that has been well developed in chemical and pharmacotherapeutic respects. However, modern medicine takes a negative view of the antipyretic method of treatment itself, since it sees in the rise of body temperature a protective reaction on the part of the organism.

But if the temperature remains too high for a long time, and there is a threat of overheating the body or even degeneration of internal organs, then antipyretica are a valuable weapon to temporarily halt an advanced temperature reaction, to give some rest to the diseased organism, and by promoting increased perspiration, to assist in the removal of toxins and other products of bacterial and febrile metamorphosis that have accumulated in the blood. The therapeutic value of antipyretica is also increased because they are good and often indispensable analgesic agents, whose effects are manifested even at doses that do not yet cause a complete antipyretic effect. Therefore, small doses of antipyretics, without causing a sharp drop in temperature in febrile patients, have a calming effect on the central nervous system, alleviate existing headaches, cause mild sweating, improve the general condition and well-being, and promote the onset of more peaceful sleep. Due to their analgesic and calming effect, antipyretica are often used in non-febrile patients in various types of neuralgia, migraine, rheumatism, etc. In addition, some of the aforementioned antipyretic agents act specifically in infectious diseases: quinine - in malaria, salicylates - in acute articular rheumatism. Finally, some antipyretica also possess special properties; for example, antipyrin acts locally as a hemostatic. When various antipyretics prescribed for a single dose act together, phenomena of synergism are observed; for example, 0.1 g of aspirin and 0.1 g of phenacetin taken simultaneously produce a somewhat stronger therapeutic effect than 0.2 g of aspirin or 0.2 g of phenacetin taken separately. N. Shavrov.