Plasmochin

PLASMOCHIN, Plasmochin, a synthetic (Schulemann, 1924) antimalarial drug; it represents N-diethylamino-isopentyl-8-amino-6-methoxyquinoline. Its production was the result of the work of scientific employees of the German firm I. G. Farbenindustrie, who, in search of quinine-like substances, tested quinoline derivatives on canaries infected with malaria (Proteosoma praecox, s. Plasmodium relictum). Then the action of P. was tested on patients with progressive tertian malaria artificially infected with malaria, and finally on patients with malaria. P. is the base, giving a readily soluble hydrochloric salt; for oral administration it is issued in the form of a salt with a high-molecular-weight organic acid; this salt represents a soluble in alcohol, almost insoluble in water pale yellow, tasteless, stable powder. The dosage of P. preparations is calculated based on the hydrochloric salt of it. Of the various species of malaria plasmodia, P. acts most strongly on the asexual forms (schizonts) Plasmodium vivax (malaria tertiana). Schizonts of Plasmodium falciparum (malaria tropica), on the contrary, are very resistant to P.; nevertheless, it destroys the sexual crescent forms (gametocytes) of this species. Besides its parasitotropic action, P. also possesses a "side" organotropic action and in large doses can cause intoxication phenomena. Among the unpleasant phenomena caused by P. are "pit-stick" pains. One of the first signs of P. poisoning—the appearance of cyanosis—depends on the formation of methemoglobin in the blood. Sometimes cardiac rhythm disturbances are observed. In severe cases of poisoning, loss of consciousness, fever, jaundice, vomiting, albuminuria have been described. In contrast to quinine, P. does not act on the muscles of the uterus and therefore is not contraindicated during pregnancy. It is also well tolerated by persons suffering from idiosyncrasy with respect to quinine. In view of the pharmacological differences between P. and quinine, it is quite rational to combine these two agents by simultaneous administration of relatively smaller doses. At present, ready-made preparations representing a combination of quinine with P. are available, namely--Plasmochinum compositum and Chinoplasmin. P. is issued by the firm I. G. Farbenindustrie (Germany) in the following forms: 1) Plasmochinum trinitrate, in tablets of 0.02 and in the form of a 1% solution of 1-3 cm³ in ampoules. 2) Chinoplasmin (plasmochin+quinine in a ratio of 1:30); tablets (plasmochin 0.01, quinine sulfate 0.3); granules (dragee) for adults (blue), containing half the amount of active principles as the tablets; granules for children (red)—four times less than the tablets; solution in ampoules of 2 cm³ (plasmochin 0.02, quinine 0.6). 3) Plasmochinum compositum (plasmochin+quinine in a ratio of 1:12.5); tablets (plasmochin 0.01+quinine sulfate 0.125), yellow granules with the same content of active principles as the tablets. In the USSR, in recent years, by the works of the Scientific Research Chemical-Pharmaceutical Institute (NIKhFI) and the Laboratory for the Study and Synthesis of Plant and Animal Products (LASIN) of the Academy of Sciences of the USSR, the synthesis of P. has been carried out. In addition, industrial production of the quinoline drug plasmocide (bis-methylene-salicylic salt of N-diethylamino-propyl-8-amino-6-methoxyquinoline) has been established. Plasmocide possesses an action analogous to P., but does not cause methemoglobinemia. By the works of the Tropical Institute of the NKZdrav RSFSR and a number of antimalarial institutions of the USSR, this drug was tested on patients and gave good results both in the sense of stopping attacks of tertian and quartan malaria, and for the destruction of gametocytes in the blood. Testing showed that taking plasmocide for one day makes the blood of a gametocyte carrier non-infectious to the malaria mosquito. P. preparations are applied in acute and chronic cases of malaria, as well as for prophylaxis in malarious localities and for "sanitation". In acute cases of malaria, if there are no contraindications to the administration of quinine, it is recommended to administer Chinoplasmin orally 3 tablets a day for 10-21 days without interruption. Attacks of fever cease on the 2-3rd day, plasmodia disappear from the peripheral blood on the 6-7th day. Children from 1 to 5 years: 1-2 times; children from 6 to 10 years: 3-4 times two red granules of Chinoplasmin a day. In malaria coma, intramuscularly or deeply under the skin 2 cm³ of Chinoplasmin solution. In cases where, after a full course of treatment (21 days), disorders characteristic of chronic malaria (cachexia, enlarged spleen) occur, it is recommended to continue Chinoplasmin 1 tablet a day. In cases where the administration of quinine is contraindicated (quinine hemoglobinuria, idiosyncrasy with respect to quinine, pregnancy), one should administer pure P. without quinine. In these cases, Plasmochinum purum is administered 3 times a day 1 tablet (0.02), but to avoid intoxication phenomena the course of treatment is carried out with interruptions, namely: after the first seven days of continuous administration, in the second and following weeks, 4 days of rest and 3 therapeutic days are given. It must be borne in mind that pure P. is little effective for stopping attacks of tropical malaria. Plasmochinum compositum is prescribed with interruptions similar to pure P. and is dosed accordingly to the content of P. For prophylactic purposes against malaria, it is recommended to administer Chinoplasmin one tablet a day, occasionally increasing the daily dose to three tablets. In this respect, according to literary data, P. even surpasses quinine, since P. possesses sporozoiticidal action and thus is a true prophylactic agent. Finally, P. preparations are prescribed to the population of malarious localities for prophylaxis. In this respect, P. has special significance due to its action on the sexual forms of plasmodia of tropical malaria (gametocytes), which are infected by the mosquito vectors. During the conduct of sanitation, all patients with malaria are subjected to systematic treatment with Chinoplasmin, while the rest of the population receives smaller doses of it: the first 2-3 days 3-2 tablets, and then 1 tablet a day. The initial administration of higher doses is intended to prevent the "provocation" of chronic and hidden forms, which can occur under the influence of small doses of P. Being a valuable achievement of science, P. still cannot completely replace quinine: