Thereby it is also to be considered that a stronger antiseptic salicylic acid could be liberated at the site of action from its salts. But this is not the case. The oral and in massive doses administered salicylic acid is converted into the sodium salt by the alkali of the intestinal fluids; it is taken up in this form and must circulate as such at the chemical reaction of the blood. Now Binz 531 has presented the theory that in polyarthritis the strong carbon dioxide tension of the blood and other body fluids (joint effusions!) would be in a position to liberate salicylic acid from its salts and has introduced some support for it.
Newer investigations by Hanzlik 532 which considered the H-ion concentration of the blood show the untenability of the CO2 tension theory. The liberation of salicylic acid requires a much higher acidity than that which is obtainable in the living blood. Actually the salicylate containing joint fluid in patients with rheumatic fever shows no free salicylic acid according to Scott, Thoburn and Hanzlik 533.
A way out of the dilemma into which the hypothesis of an etiotro- pic action of salicylic acid in rheumatic fever has been harmed by experimental investigation is opened through the findings of Bondi and Jacoby. 534 They seem to speak for a certain organotrophy of salicylic acid for inflamed joints, because the joints of rabbits which were infected by staphylococci contained more salicylic acid than those of normal rabbits. Such an enrichment of salicylic acid salts in the inflamed tissues would be explained without further trouble from its greater blood supply because according to Bondi and Jacoby the blood has the greatest relative amount of salicylic acid. But now newer investigations 535 have brought definitely opposite results, naturally in arthritis which can be experimentally produced in rabbits by the local application of oil of mustard and croton oil. Finally it is proven by Scott, Thoburn and Hanzlik 536 in patients with rheumatic fever that the salicylate content of the joint fluid is less than in the blood. Thereby the greater affinity of salicylic acid for the inflamed joint cannot be maintained.
MANNER OF ACTION IN RHEUMATISM —————————— In what relation now from a clinical viewpoint does the specificity of salicylic acid stand in acute rheumatic fever? The prompt lowering of the temperature with the outbreak of sweating and the diminution of inflammatory manifestations in the joints, particularly the pains, is so striking with great doses, that indeed one might well think of a specificity. Recently R. Sicard 537 has shown from personal observations as well as those of others that the joint manifestations and the fever are not rarely entirely refractory from the start against the salicylic acid therapy. Moreover it is striking that under the use of salicylic acid in maximal doses, the return of joint symptoms is frequent, and further that cardiac involvement is not avoided nor in any way favorably influenced. 538 But since the cardiac manifestations of the infections disease, polarthritis rheumatica are characteristic, indeed according to many authors an essential part, this must create doubt of the specificity of salicylate salts. Against a specificity in the sense of a one sided selectivity also speaks the fact that other agents which do not contain the salicyl group (particularly atophan with its chinolin group) have the same antipyretic and analgesic action in joint rheumatism, indeed, Hanzlik, Scott and Gauchat 539 have shown that the same or almost equal results can be obtained in rheumatic fever by a combination of analgesic and antipyretics of the type of morphine and quinine, where there is not be least relationship to the salicylate group. But on the other side salicylic acid effect is not limited to acute rheumatism but the analgesic and antipyretic actions are used just as much in many other states of disease. So there is no basis for seeing in salicylic acid more than a pure symptomatic characteristics in this disease. In addition to the antipyresis and analgesia, there is also the lessening of joint swelling. One may designate the action in rheumatism also as a polysymptomatic one so that in this case salicylic acid is a syndrome remedy.
The mechanism of salicylic acid action on the symptoms of joint rheumatism has been explained only to a small extent through numerous studies. In regared to the antipyresis, salicylic acid in the usual small and large doses widens the peripheral vessels, in particular those of the skin, probably through an action on the central nervous system, at the same time with an increase of sweat. Increased heat radiation occurs and in the febrile it is particularly great. While increased heat radiation is hardly evident in the healthy, it is distinctly evident in the labile heat regulation in fever. The production of heat does not seem to be influenced at least by the doses employed clinically. It is established that there is an increase of nitrogen, uric acid, phosphate and sulphate excretion under large doses of salicylic acid.
There is also a lowering of uric acid content of the blood with increased amounts in the urine. 540 After discountinuance of salicylates the uric acid in the blood again increase and the quantity in the urine diminishes. 541
Moreover with doses of salicylic acid under 2 grams, variable output of uric acid in the urine is found. 542
On the other side, very large doses in rats also cause a diminution of nitrogen excretion in consequence to the nephritis which develops.
The influence on water excretion behaves correspondingly. With moderate doses the diuresis is increased; in animals the renal volume increase through widening of the vessels and there is only a transient decrease in the output of urine 543; with doses under 2 grams according to Willy 542 there is no increase in output. With large doses. clinically maximal, of sodium salicylate the amount of urine is decreased and albuminuria appears (and eventu- ally casts) in the urine. 544 In animals nephritis has been found histologically 545 and also in the human at autopsy. 546
The increase of protein conversion under large doses of salicylic acid permits an increase in heat production to be assumed and this is present also according to experiments by Isenschmid. 547 But for the antipyresis, it is decisive that under the conditions of the already febrile increased metabolic, the heat radiation predominates.
Formerly one perceived a close natural connection between the acute rheumatic fever and the uric acid content of the blood and made the increased excretion of uric acid responsible for the favorable influence of salicylic acid. If this hypothesis is not clinically verified in gout, then it is to be doubted in an acute infectious disease as acute rheumatism.
It is exactly the detailed investigations on the N-metabolism under salicylates which have led to the conception that salicylic acid lowers the permeability of the kidney for uric acid and it has often been assumed that the increased permeability of the kidney for other residual products and also the hypothetical toxin of the excitor of joint rheumatism existed. With this there would be in addition to the marked excretion through sweat, a further excretion through the kidney, two ways of canalization, but still no “created” defense of the organism, as one might say.
The actions on the heart and circulation known up to the present cannot contribute much to the explanation of the antipyretic action.
Sensitive persons react to small doses of salicylic acid with acceleration of the pulse and sensations in the cardiac region.
How much the disposition contributes to the action of salicylic acid can be perceived from the existence of a (so-called paradox) increase in temperature which is independent of the dose of the drug. Lewin states 548: “It is evident 1/2-1 hour after the ingestion and is usually introduced by a chilliness which may last over an hour.Following this is a marked sensation of heat and the body temperature itself rises to 41 C. The fever may remain at this height up to two days and then spontaneously diminishes.
In these cases there is, what was striking to me because it is usually so common, only a fairly moderate secretion of sweat.”
Since the heat production is almost constantly increased by salicylic acid, perhaps the last observation of deficient sweating explains the fever. Moreover it is note worthy, that besides the antipyresis by “canalization,” a stimulative action is also possible under certain conditions, in which an action of much occur in the sense of the simile rule.
The reduction of inflammatory manifestations in the joints according to all appearances is not a local phenomenon which lessens or prevents oedema through alteration of vessel permeability. The action seems to occur rather through a central reduction of the circulation and also to a certain extent independent of the mechanism of antipyresis. Artificially chemically induced oedema is neither prevented nor improved by sodium salicylate.
Leeser, a Consultant Physician at the Stuttgart Homeopathic Hospital and a member of the German Central Society of Homeopathic Physicians, fled Germany in 1933 after being expelled by the German Medical Association. In England Otto Leeser joined the staff of the Royal London Homeopathic Hospital. He returned to Germany in the 1950s to run the Robert Bosch Homeopathic Hospital in Stuttgart, but died shortly after.
Otto Leeser wrote Textbook of Homeopathic Materia Medica, Leesers Lehrbuch der Homöopathie, Actionsand Medicinal use of Snake Venoms, Solanaceae, The Contribution of Homeopathy to the Development of Medicine, Homeopathy and chemotherapy, and many articles submitted to The British Homeopathic Journal,