EFFECT UPON MALARIAL PARASITES 1201 



depressant, producing a fall in the arterial pressure, with, decrease in the 

 pulse-rate and strength. This is an important matter, to be remembered in 

 administering the drug to the old and the feeble, especially by intravenous or 

 intramuscular injections. On the nervous system it acts as a stimulant, and 

 also increases the flow of blood to the brain. In the tissues it is partly 

 destroyed by oxidation, and therefore the whole quantity administered is 

 hardly likely to be obtained in the urine. Excretion takes place by the 

 kidney almost entirely in the form of quinine dihydroxyl. It can be recovered 

 from urine by acidulating with sulphuric acid, treating with solid picric acid, 

 filtering until clejar, digesting with 3 per cent, caustic soda solution, and 

 extracting with chloroform, from which the quinine can be obtained by 

 evaporation. Ramsden and Lipkin have described a new process for isolating 

 quinine from urine {Annals of Tropical Medicine and Parasitology, May, 191 8). 



When given in large doses, the cerebral congestion which it produces causes 

 buzzing in the ears, deafness, due to congestion of the middle ear, and head- 

 ache, both of which can be treated by bromides, with or without a little ergot. 

 It may also cause erythematous, erythemato-papular, vesicular, and urti- 

 carial eruptions. 



Quinine Hcsmoglobinuria. — In persons who have suffered from malaria 

 there is no doubt that quinine can cause haemoglobinuria, but the way in 

 which it acts is doubtful. Stephens believes that the haemoglobinuria stands 

 in no relationship to the dose of quinine, and, further, that a second dose may 

 not produce the result, and that it is the blood condition of the malarial patient 

 which is the determining factor. Our experience has tended to show that 

 there is a direct relationship between the quinine and the haemoglobinuria. 

 Quinine acts in this way by causing haemolysis of the red corpuscles. Stephens 

 and Christophers found that 0*00 1 to 0-00082 gramme of quinine haemolyzed 

 I c.c. of a suspension of normal human red cells at 37° C. The haemolytic 

 action naturally increases the quantity of bile produced. For further remarks 

 on this subject, see the next chapter, on Tropical Haemoglobinurias (p. 1214). 



Quinine Amblyopia. — Amblyopia may result as the effect of large doses of 

 quinine, and appears to be due to constriction of the retinal arteries in tem- 

 porary cases, and to degeneration of the retinal ganglion cells and their 

 processes in permanent cases (see also p. 2007). 



Quinine Fever. — -In latent malaria a small dose of quinine may occasionally 

 provoke a febrile paroxysm. This has been compared to the action of a 

 small dose of salvarsan in provoking an exacerbation of symptoms in 

 latent syphilis (Herxheimer's reaction). 



Action on the Uterus. — Quinine appears to act upon the uterus, and may 

 therefore produce an unpleasant effect in pregnancy, though whether this is 

 really due to the quinine or to the malaria, or to the two combined, is doubtful. 



Effect upon Malarial Parasites. — Quinine appears to particularly 

 alfect the merozoites, trophozoites, and schizonts, and to act much less vigor- 

 ously, if at all, upon the gametocytes. 



It appears to act most vigorously upon the merozoites, perhaps because 

 they are free in the plasma ; next upon the young trophozoites, whose cyto- 

 plasm is broken up, and finally it and the nucleus destroyed; but it has much 

 less effect upon the fully grown schizont, not preventing sporulation. 



With regard to the gametocytes, it probably has a deleterious action upon 

 the young forms, but certainly not upon the fully grown micro- and macro- 

 gametocytes. It is thought probable that it may act upon the very old form 

 of microgametocyte, but this cannot take place, as a rule, with regard to the 

 ordinary fully grown microgametocyte, for anophelines can be infected by 

 the blood of persons containing the two kinds of gametocytes even when 

 treated vigorously with quinine. On the macrogametocyte, particularly that 

 of Laverania malarics, it appears to have no action. Hence, to get the full 

 effect of quinine on the parasites it must be present in the blood at the time 

 of sporulation, in order that it may kill the merozoites, young sporonts, and 

 schizonts. In order to produce this effect, it is judged that the quinine must 

 be present in the blood in a strength of at least i in 20,000. According to 

 Thomson, though quinine has no direct destructive action upon the crescents, 



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