Irritants

IRRITANTS belong to the oldest groups of medicinal agents. Since, according to the concepts of old medicine, irritation of the skin could lead to the distraction of a "painful principle" from internal organs to the outside, Irritants received names corresponding to these concepts, which have persisted until recently: derivantia (from Latin derivo—I distract); revulsiva (from Latin revello—I distract, I pull out), excitantia (from Latin excito—I extract, I draw out), epispastica (from Greek epispastikos—drawing). Kobert proposed a more precise, though rarely used name—dermerethistika (from Greek derma—skin and erethiso—I irritate). As Irritants, substances are used primarily that, due to their volatility or easy solubility in lipoids (or both properties), easily penetrate the skin, namely: iodine tincture, ammonia, chloroform, alcohol, various volatile essential oils, turpentine, mustard oil, etc. However, among Irritants, there are also substances that penetrate the skin with difficulty, e.g., cantharidin. Since all these substances are very different in their chemical composition and structure, a chemical or pharmaceutical classification of Irritants is very difficult (see below). When using Irritants, one should distinguish those having therapeutic significance: a) a local reaction arising at the site of application, b) a reflex reaction arising in organs distant from the site of irritation, and c) a reaction having no therapeutic significance, associated with absorption and the entry of Irritants into the blood. This last effect, secondary to the therapeutic one, if it is expressed strongly enough, can lead to poisoning (cf. the danger of kidney damage upon absorption of cantharidin). The local reaction, accessible to direct observation, has always attracted the most attention, serving in its time as the basis for the doctrine of Irritants as "distractors." This local reaction, depending on the choice of agent, and primarily on the duration of its application, leads to irritation of varying degrees, starting from mild, rapidly passing redness and swelling of the skin and ending with sharp inflammation of it with the formation of blisters, suppuration, ulcers, and eschar (for a detailed description of the skin irritation process, see Dermatitis, signs of dermatitis, and dermatitis of exogenous origin). Due to the fact that for obtaining a certain degree or character of irritation, some substances were and are used preferentially over others, a classification of Irritants has long arisen, which can be called clinical. It distinguishes: 1) Irritants causing redness of the skin, rubefacientia, e.g., essential mustard oil; 2) Irritants causing the formation of blisters, "blistering agents," vesicantia, e.g., cantharidin; 3) Irritants causing the formation of pustules, pustulantia, or suppurantia; "suppurating" Irritants, not used in modern medicine, include croton oil, tartar emetic, etc. The strong action of some Irritants (e.g., ammonia) leads to the death of tissues, i.e., an effect characteristic of the group of cauterizing agents, caustica, s. necrotica, s. escharotica. Experimental studies of recent years have revealed significant differences in the processes of skin irritation caused by various substances, and therefore Heubner (1925) proposed a pharmacological classification of Irritants. The latter, keeping in mind not only Irritants (i.e., a pharmacotherapeutic group), but Irritant substances in general, seeks to divide the latter according to the signs of their predominant action on certain tissue elements. In this classification, the following are distinguished: 1) poisons irritating sensitive nerve endings (e.g., veratrine, the active principles of pepper and paprika); 2) cellular poisons (e.g., cantharidin); 3) capillary poisons (e.g., dionin); 4) capillary and nerve poisons (e.g., histamine); 5) cellular poisons with simultaneous action on capillaries (e.g., arsenic, mustard gas); 6) cellular poisons with simultaneous action on capillaries and nerve endings (e.g., essential mustard oil). A strict distinction between individual groups of Irritants, however, is not possible, since upon damage to cellular elements, decay products are formed (histamine or substances acting similarly to it), which may prove active in relation to nerve and vascular elements. Since, at the same time, their therapeutic use is still based primarily on empirical data, the clinical classification continues to retain its significance. Indications for the use of Irritants are very diverse. Despite the complexity of the effect they cause, it is still possible to single out in some cases of this application the predominant significance of the irritation of sensitive nerve endings, i.e., a reflex reaction, and in others—inflammatory irritation, i.e., cellular and vascular reactions. Energetic irritation of a limited area of the body surface with chemical agents is used for the purpose of reflex excitation of "vital centers" in states characterized by acutely arisen weakening of respiration, blood circulation, and loss of consciousness (fainting, poisoning with narcotic substances, etc.). Being the most quickly performed and most accessible measure, it is often quite effective, and in cases where subcutaneous injection of various excitantia and analeptica (caffeine, camphor, etc.) may prove ineffective due to sharp disturbances in absorption and blood circulation, it has a special advantage. Since in the states considered here, the excitation of the centers of the medulla oblongata is of particular importance, the choice of the site of irritation is determined by those reflexogenic zones from which this excitation is particularly easily evoked. Most often, irritation of the mucous membranes of the nose is used for this, for example, sniffing ammonia, less often—the mouth, e.g., pouring a few drops of cognac into the mouth. Despite the fact that the method of applying Irritants to mucous membranes could be considered separately for theoretical reasons (Kobert distinguishes an independent group of agents irritating mucous membranes—phlegmerethistica, from Greek phlegma—mucus), it is completely analogous in the mechanism of its action to skin irritation. Of the skin-irritating agents in these cases, a mustard plaster is often used, which is usually placed on the region of the heart or epigastrium. An analogous reflex effect is given by sufficiently strong mechanical irritation (e.g., tapping on the back surface of the hand), and in some manipulations used in fainting states, one can find elements of all three mentioned methods of irritation (e.g., rubbing the temples with cologne—mechanical and chemical irritation of the skin and chemical irritation of the nasal mucosa). Along with the intensive, but short-term and more or less strictly localized application of Irritants, they are also used for the purpose of moderate excitation (or toning) of the central nervous system in general, and especially of the vegetative innervation and its trophic function, for which less intensive but more prolonged irritation of large skin surfaces is used. The latter can directly lead to an improvement in well-being and the emergence of a feeling of vigor and strength ("Lustgefühl" and "Kraftgefühl" of Goldscheider). Indications for such use of Irritants usually coincide with indications for various physiotherapeutic procedures (see Hydrotherapy, Massage, Physiotherapy) and partly coincide with them. Such are rubdowns with aromatic vinegar, aromatic alcohol, etc., in weak patients, especially during prolonged febrile states, rubdowns with green soap, ointments with a small content of turpentine, etc., in outpatients (often for various forms of tuberculosis). Irritants are especially often used for the purpose of calming pain, and given the lack of clarity of the mechanism of their analgesic action, some authors (Richaud) still consider it possible to justify the former names of Irritants by their significance as "pain-distractors." Since this "pain-distraction" occurs upon irritation of the sensitive nerve elements of the skin, it is undoubted that in its mechanism, reflex action on the central nervous system, which changes its reaction to impulses coming from the primary painful focus, is of significance. The calming of pain, as observations of a number of generations of physicians have shown, is achieved with particular success with certain correlations of the localization of pain and the site of application of Irritants, and it must be considered that in this effect, a large role is played by those processes of interaction of cutaneous and visceral innervation that occur within the limits of the same segment of the spinal cord. The possibility of such interaction became clear after the works of Head, Mackenzie, Verneuil, and other authors (see Pain, symptomatic; Vegetative nervous system—afferent pathways and reflexes; Head zones). These works established that in diseases of internal organs, zones of increased sensitivity arise on certain areas of the skin surface. The emergence of Head zones is explained by the irradiation of excitation from sensitive conductors coming from internal organs to those nerve cells that perceive impulses from the corresponding area of the skin. This same irradiation explains the ability to localize pain in lesions of internal organs.

A comparison of the localization of Head's zones and the areas of skin that have traditionally been and are still chosen for the application of irritants in diseases of internal organs speaks extremely convincingly in favor of the segmental nature of the "analgesic" reflex. Besides changes in the reactivity of the central nervous system, skin irritation can also reflexively affect the processes occurring in the diseased organ itself. Since changes in blood supply, associated with fluctuations in the lumen of blood vessels, and spasmodic contractions of the musculature play a significant role in the origin of pain in internal organs and skeletal muscles, the analgesic effect of irritants may also depend on the reflex dilation of vessels and relaxation of the musculature of the diseased organ. Given the limited knowledge, on the one hand, of the anatomical-physiological substrate of cutaneo-visceral reflexes, and on the other hand, of the nature of those pathological processes upon which a reflex effect is possible to one degree or another, the use of irritants (as well as their selection and "dosage") continues to remain empirical. The local effect of irritants is used in dermatology in cases where one seeks to induce an influx of blood to the affected area of the skin, and in a number of cases, to exacerbate a sluggish inflammatory process. The therapeutic use of inflammatory (or near-inflammatory) irritation of healthy skin requires special consideration. It was widely used in the past and is often used in modern medicine, most often for inflammatory processes in various internal organs. While in the past it was believed that the hyperemia of the skin caused by irritants was capable of "diverting" blood from the underlying organ, according to Bier, on the contrary, it extends to the underlying organs (an opinion shared by such an eminent pharmacologist as H. Meyer), and therefore can lead to a reduction in pain and the resolution of the inflammatory process in these organs, just as it occurs with hyperemia caused by heat or other methods (see Bier's method). The therapeutic significance of inflammatory skin irritation is currently also explained by the fact that various products of increased metabolism and cellular decay are formed at the site of irritation; the latter, due to the increased permeability of the vessels of the inflammatory focus, easily enter the blood and, being highly active in their ability to act as agents of so-called non-specific therapy, produce an effect analogous to the parenteral administration of foreign protein, autohemotherapy, etc. (Petersen et al.). Special studies devoted to the question of the effect of irritants and skin irritation in general on the number of leukocytes in the circulating blood have not yielded consistent results: some authors observed an increase, others a decrease, and some a decrease followed by an increase in the number of leukocytes. Since a sequentially occurring reduction in pain and improvement in well-being is usually noted during protein therapy procedures, it should be noted that an analogous effect of irritants, in addition to their reflex action discussed above, can also occur in this way. To confirm these views, Petersen, Weichardt, and others also refer to the fact that the use of irritants has become widespread in the same diseases for which protein therapy has been particularly willingly used in recent years (various rheumatic and rheumatoid diseases, etc.). The peculiarity of the non-specific effect when using irritants, in contrast to protein therapy agents, is that it is direct only in relation to the skin tissue, while the humoral effect occurs indirectly, due to the absorption of substances formed during skin irritation. Therefore, irritants can be considered as agents that increase the immune function of the skin, represented in the doctrine of so-called phylaxis. To induce inflammatory or similar types of skin irritation, rubefacientia are mainly used (lubricating the skin with iodine tincture or applying mustard plasters, which gives a more intense and longer-lasting effect); vesicantia (cantharides preparations) are used significantly less often. Pustulantia, which were used in old medicine, have been abandoned entirely, as inducing suppuration of the skin extremely complicates the doctor's task and must be considered contraindicated. The ability of irritants to produce an effect analogous to that achieved with protein therapy makes understandable the breadth of indications for their use that existed in old medicine, which incorrectly interpreted their mode of action, and at the same time destroys the skeptical attitude toward them that existed in recent decades, when the mechanism of this action was unclear. All of the above speaks to the extreme diversity of processes that arise when using irritants, and thus to the difficulty of analyzing the therapeutic role of individual processes. The fact that it is expedient to use all these processes in the pursuit of a therapeutic effect is well proven by the fact that the most favored (in other words, empirically most preferred) of the irritants used is mustard oil (resp. mustard plasters), which, as follows from numerous studies (see Heubner's classification above), possesses the most versatile effect on the skin. Contraindications to the use of irritants are, first of all, diseases of the skin itself, which limit the use of irritants at the site of existing irritation, states of increased sensitivity of the skin to irritation (the latter can be selective in nature—cf. intolerance to iodine, etc.), as well as diseases of the organism that can disrupt the reversibility (resp. healing) of the irritation (e.g., diabetes, in which there is a tendency to skin gangrene), which is why the use of irritants in weak patients in general requires special caution. Also contraindicated is the repeated or prolonged use of irritants, especially in cases of using those agents that can be absorbed in quantities sufficient to produce a resorptive effect (cf. irritation and inflammation of the kidneys when using blistering plaster, as well as turpentine). In cases where this danger does not exist, when using irritants repeatedly, one should change the site of irritation to avoid severe skin inflammation, which can lead to difficult-to-heal ulcers. Of the individual groups of irritants distinguished by various authors, the following groups are of particular importance (according to Kobert): 1) salts (brine, sea, mud baths); 2) acids, mainly volatile: carbonic acid (natural and artificial carbonated baths), formic and acetic acids; 3) alkalis, both volatile (ammonia) and non-volatile (potash, soda, sulfurated potash, green soap); 4) iodine; 5) essential oils, resins, balsams, camphors (mustard, rosemary oil, turpentine, camphor, etc.). This group includes numerous irritants of folk medicine, such as garlic juice, crushed onion, and many others; 6) cantharides. Irritants are most often used in the form of liquids or liquid ointments, with substances often used as vehicles that are themselves capable of causing skin irritation (water, liquid paraffin, fatty and essential oils, alcohol, chloroform, etc.), as well as in the form of more or less thick ointments, plasters, ointment sticks, and pastes. One of the most favored irritants—mustard flour—is usually used in the form of mustard paper.