Presented for the I.H.A., Bureau of Homoeopathic Philosophy, June 1943.
(PRONTOSIL RUBRUM).
Homoeopathy has not remained stationary-DR.HIGINIO G. PEREZ, Medical Philosophy, page 446.
The real gains of modern medical science are not in conflict with the fundamental principles of the Hahnemannian Therapeutics- DR. H. LUNA CASTRO.
All the gains of modern medical science and most particularly those of pharmacology, whatever their source or origin may be, however much they may appear to differ from the Hahnemannian criterion, must indeed be studied without prejudice with all fullness, serenely and minutely in order that without abandoning the philosophic criterion of the homoeopathic doctrine, the new discoveries may all be utilized by the followers of Hahnemann for the benefit of suffering humanity.
In 1908, paramide-benzene-sulphonamide was obtained for the first time, a product that has no relation whatever to medicine or therapeutics. One year later Horlein, Dressel and Kothe obtained azoic coloring with sulphonamidic groups for the purpose of fixing colors upon woollen cloth.
It was not until 1932, when Gerard Domagk, chief of the laboratories for experimentation upon animals in the I.G.Far- benindustrie Aktien ges. in Frankfurt-on-the-Maine, Germany, who experimentally demonstrated the great efficacy of several azoic compounds upon hemolytic streptococcemia of the mouse.
Later on Heidelberg and Jacobs demonstrated that some azosulphadated compounds have in vitro a bactericidal action in this very year Klarer and Mietzsch obtained a patent of chlorhydrate of sulphamide-diamino-azobenzene or sulphamido- chrisoidine, under the name of prontosil rubrum.
The starting point then of the new chemotherapy inspired in the initiated with the arsenicals by Uhlenhut, and carried on to such a happy conclusion by Ehrlich, is due to Domagk. Therefore Domagk inaugurated a real innovation in therapeutics with the azoic compounds of series of red preparations, that very soon reached a great reputation owing to their wonderful results obtained in Dusseldorfs clinic.
Later on Ernest Fourneau, of the Pasteur Institute of Paris, in collaboration with Levaditi, Trefouel, Bovet and Nitti, found the radical para-amino-phenil-sulphamide, that constitutes the principal antistreptococcic efficacy and obtained the new preparation of azoic type of the red series analogous to prontosil under the name of rubiazol.
Beginning with these interesting discoveries investigators have appeared from different parts of the world, some of them supplying theories about the action of different azoic products and others obtaining new products, it being proved by some authors that the diazoic group is not fundamental to developing the antistreptococcic al chemotherapic action for which they were searching and the very essence of its action rests exclusively in the para-amino-sulphonamide.
Along with these new investigations para-amino-benzene- sulphamide, a white body, very slightly soluble in water, is obtained, which initiates the stage of the sulphamidated chemotherapy of the white compounds.
Later on, Launoy and his collaborators obtained soluble compounds of a liquid, colorless, well tolerated in subcutaneous injections dowered with marked antistreptococcal properties, obtaining the para-amino-benzene-bisulphite-sodic-formaldehyde.
Since then the chemists have not ceased to look for bodies from the group of sulphamides to employ them through oral and parenteral channels resulting in greater antimicrobian activity and at the same time less toxicity for the organism. (Sulphophenol, disulphamide, sulphathiazol, sulphamidopyridine, etc., etc.).
Mietzsch and Klarer, Girard, Butle, Fourneau, Gley, Dagenan, Eubasin, Penfold, Quastel, Mayer and others, in their investigations of a chemical and pharmacological order, reached these two conclusions: 1. Dissociation of diazoic leads to para-amino-phenil-sulphamide, which through processes of oxidation supplies hydroxylamine to the organism; and 2. The azoic is combined with the proteins giving place to azoproteidic compounds, whether sanguineous or microbian, appearing in intimate union the defensive elements of the antibodies type.
The aptenous, true pro-antibodies existing in the human organism, in this case are united with the azoproteidic antigens giving place to the true antibodies.(Landsteiner and MacIntosh.) Therefore, in this system of transformation by sulphamides, the hydroxylamine formed as a result of their administration acts like a true catalyzer, although its presence is in imponderable or infinitesimal quantities favoring in this way the defensive reactions of the organism by accelerating them.
Sulphamides have no antiseptic action (Wolff and Julius) and it is to be observed that in human blood without microbian elements the sulphamides in massive doses give place to metahemoglobinuria and sulfohemoglobinuria, accidents of toxic manifestation.
The in vitro and in vivo action of sulphamides is the weakening of resistance of the pathogenic agent, upon which they act (streptococcus, pneumococcus, meningococcus, etc.) originating their employment a diminution of aggressivity of the toxins and preventing their reproduction. In divers biological media (blood, serum, urine) the inhibition of the microbes development is obtained with concentrations from 1 to 10000 and from 1 to 25000.
The first thing that comes to our attention in the study of sulphamides is the discordance between the action in vitro that is little evident and its intense action in vivo. On the other hand, their action is not proportional to the ingested quantity, nor even to their sanguineous concentration, when an optimus dose is obtained the relation between the dose and its therapeutic action is broken. (Burnett and Jeansalle.).
Colebrook, Long, Bliss, Kleen, Lockwood, Mayer, Flemming, etc., who have tried to explain in different ways the action of sulphamide preparations in vivo and in vitro have demonstrated that these act in the same way upon the mobile cells of the organism (erythrocytes, leukocytes, spermatozoa, etc.).
The sulphamides, as one has said, do not act upon the pathogenic agents of infection in a destructive manner, and only prevent the development and virulence of these, proving that their action is bacteriostatic exclusively. (MacLean, Rogers, Flemming, etc.).
Sulphamido-chrisoidine or prontosil rubrum has a high power of diffusion and the concentration that it reaches in the blood and in the tissues is proportional to the dose administered and we must take into account that its action is not innocuous in order to avoid the toxic accidents to which it gives rise. The ingested remedy does not circulate nor is it eliminated in its totality in the same form that it is ingested. In the hepatic cell the sulphamido-chrisoidine suffers an acetylation process that neutralizes its toxicity.
Prontosil rubrum is principally eliminated through the urinary channel, its prolonged use originating nephritis phenomena and facilitating the formation of calculus; the urine is alkaline without an increase in the quantity of phosphates.
It is interesting to note that sulphamides, whichever might be the mode of administering them, cross the choroidal plexuses and meningeal zones reaching as far as the cephalorachidian liquid in lower concentration than that found in the blood. (Hodes and Gimbett.).
The white compounds not azoics do not color the urine. With prontosil rubrum, in the same way as with azoic compounds, three hours after having ingested them, the urine takes on red-orange or mahogany red color.
Once the sulphamido-chrisoidine has been administered trifling, serious and even mortal accidents have been observed. (Schwentker.).
Prontosil rubrum in its effects upon the digestive apparatus produces nausea, gastralgias, anorexia, vomiting and diarrhoea, hepatitis and jaundice.
In the line of sanguineous accidents, phenomena have been proven such acidosis, cyanosis, metahemoglobinemia, bilirubinemia, hemolytic anaemia, leukopenia and more especially neutropenia and mortal agranulocytosis.
Under the nervous accidents it is capable of originating asthenia, nausea and dizziness, depression, drowsiness, cephaleas, mental confusion, fever, ringing in the ears, nervousness and even paralysis of the lower limbs.
Under genitourinary accidents it is capable of producing micro- or macro-scopic hematuria, renal colics, crystalluria, lithiasis, albuminuria and anuria that may be mortal; also of spermatogenesis disturbance.
Upon the skin it goes so far as to produce erythemas in general, pruritis, exanthemas of scarlatiniform, urticarian, morbilliform, purpuriform, petechial and pustular type. OEdema of angioneurotic type, melanodermas and photosensibilization.
All that is known about sulphamido-chrisoidine or prontosil rubrum, through laboratory studies, as well as from their toxic effects and clinical results, must be entirely made use of in order to know and study their action from the point of view of the Hahnemannian criterion.
