In addition to the modern invaluable antipyretics, a large number of drugs of vegetable, animal, and mineral origin have been recommended, sometimes empirically, again on hypothetic grounds. But so far none of them can lay claim to general recognition, although, on account of the intolerance manifested by many individuals to quinin, it would be very desirable to have an effective substitute.
In proving the antimalarial properties of a drug, great caution must be exercised. It must not be forgotten that our mild malarial paroxysms frequently recover spontaneously after the patient is put under better hygienic conditions, and that even infections with parasites of the second group have been observed to pass over without medication. The antimalarial efficiency of a drug, therefore, can be demonstrated in a severe malarial region only by an experienced observer.
In spite of the deficiency in our remedies we intend to discuss several which possess some, if only a slight, antimalarial effect, since under circumstances a trial of remedies other than quinin becomes obligatory. We refer to cases in which quinin has proved ineffective after long administration, and ones manifesting an intense idiosyncrasy against it (hemoglobinuria, etc.).
We turn first to the other substances obtained from Peruvian bark which show a similar composition to quinin. These are cin chonin, cinchonidin, chinidin, and chinoidin. Of these four, cinchonidin alone appears to be of value (Spitzner), though many writers, like Marty, condemn it. According to Marty, three or four times the dose of cinchonidin acts less efficiently than a simple dose of quinin, not to mention the fact that it is much more toxic. De Brun, on the contrary, obtained very satisfactory results from its sulphate.
Cinchonidin hydrobromate or hydrochlorate may be employed. Both are soluble in their own weight of water.
Cinchonin and chinidin are more questionable in their effect and more toxic than cinchonidin. They are, therefore, best avoided.
Euchinin, the ethyl carbonate of quinin, has been lately recommended by von Noorden. In solution it reacts alkaline. The hydro chlorate is readily soluble in water and has a very repulsive taste; the base and its tannate are soluble with difficulty and manifest only a slightly bitter taste. Euchinin is useful when children and the especially susceptible are concerned. It is readily administered in milk, cocoa, etc. On account of its slighter solubility, a dose double to that of quinin should be given. I have tried it in two cases of mild malaria with satisfactory results. Panegrassi and Conti have had good results in 20 cases. They claim to have observed no bad effects.
These substances have been abstracted by Laborde, Grimaux, and Bourru from China cuprea. Cuprein is an alkaloid of which quinin is the methyl ether (Grimaux and Arnaud).
The formulas of the whole series are:
C19 H21 NOCH3..............................quinin (methylcuprein).
C19 H21 NOC2 H5............................chinsethylin.
C19 H21 NOCH3 H7...........................chinopropylin.
In experiments on malarial patients it was found that cuprein was less, the other two more, effective than quinin sulphate. The relations were:
Chinopropylin showed associated toxic effects (tinnitus aurium, vertigo, nausea); cuprein and chinsethylin showed not any or at most very slight toxicity. The results of these investigations demand other experiments. The dose is evident from the foregoing figures.
Phenylchinaldin, a derivative of quinin, has been recommended by Tappeiner on account of its intensely poisonous effect on infusoria.
With amounts of 0.8 and 1.5 gm. pro die no unpleasant effects were noticed. The paroxysms were suppressed for a few days, but returned again, even under continued administration of the drug. The parasites did not disappear from the blood.
Among the phosphins, methylphosphin and dimethylphosphin were suggested by experiments of Tappeiner. They were administered in daily doses of 1 to 1.2 gm. Their effect was also only transitory (see Tappeiner, Grethe, Mannaberg). The failure of the quinin derivatives and the phosphins is of considerable theoretic interest. It would appear that quinin had, in addition to its general poisonous action on protozoa, a special property which made it capable of acting on the parasites inclosed in corpuscles within the circulation.
Phenocoll hydrochlorate has been administered with success by several investigators (Albertoni). Pucci had, among 20 cases, 17 cures, 2 undetermined, and 1 negative result. He employed it in some cases in which quinin had failed. Two cases of quinin hemoglobinuria were among those that were cured. Injurious associated effects were not observed.
Pucci gives the drug in doses of 0.15 to 0.25, four to five hours before the paroxysm. Throughout the day he gives 0.5 to 1.0 or even 2.0 to 2.5, and to children, 0.5 to 0.75. The remedy must be administered four to six days in order to be effective. Negative results have likewise been reported (F. Plehn, Geronzi).
Analgin has been recommended by Raimondi. Moncorvo obtained good results in children with daily doses of 0.25 to 0.30. Even the youngest children bore the drug well.
The dose for adults is 1.5 to 2.0. Analgin is insoluble in water and is consequently administered in powder form. Long continuous treatment with it is not advisable, since we cannot explain the red color of the urine which accompanies it.
Antipyrin and antifebrin act only symptomatically. Register recommends their exhibition before quinin, since quinin acts better during apyrexia, when it destroys even the crescents (?).
Methylenum ccendeum purum (methylene blue) was recommended by Ehrlich and Guttman. It has been frequently experimented with, sometimes with satisfactory (Bourdillon, Rottger, Fereira, and others), again with unsatisfactory (Ketli Mya, Plehn, and others) results. It must be chemically pure, and should be administered in capsules in doses of 0.1 gm. The daily dose for adults is 0.5 to 0.8; for children, 0.25 to 0.5.
Soon after taking, the urine becomes yellowish green, later intense blue. As associated effects, vomiting, diarrhea, and strangury have been sometimes observed. In order to avoid the last it has been recommended to give, at the same time, several knife pointsful of powdered nutmeg.