Post by Kukul-Kan on Dec 6, 2003 9:26:42 GMT -5
DRUG SENSITIVITY IN WHITES AND NEGROES
Further information on racial differences in physiology and disease carne from testing synthetic antimalarials during and especially after World War II. Occasional individuals proved "sensitive" to the antimalarial drugs, that is they developed haemolitic anemia due to the destruction of red blood cells The characteristic symptoms were demonstrable in occasional individuals who had been given primaquine (a quinine-like drug), such common drugs as acetanilid-often used in cold remedies-and the sulfanilamides. A small proportion of individuals maintained on doses of primaquine or acetanilid exhibited drug sensitivity but the vast majority of individuals did not.
When the proportion of drug-sensitive individuals was investigated in different geographical races, interesting results immediately appeared. The incidence of multiple-drug sensitivity in American "whites" proved to be low, 1% or even less. Among 1000 prisoners treated with primaquine and described by Dern, Beutler and Aving ('55) the incidence of sensitivity was 0.1%. However, a larger proportion of American Colored prisoners developed haemolitic anemia following the drug treatment. Among them, proportions of sensitive individual s ranged from 5% in one test to 11% in another group and 12% in yet another group. The true incidence of drug-sensitivity in the American Colored population is therefore close to 10% as shown in the following table.
Studies on the blood of drug-sensitive and drug-insensitive individuals have shown marked differences in the stability of blood cell glutathione. To quote Beutler, Robson and Buttenwieser ('57) "When primaquine was administered to non-sensitive subjects there was no change in the red cell GSH (reduced glutathione) level. When primaquine was administered to a sensitive subject, however, there was an abrupt fall in the GSH content of the red blood cell to about one-half of the original already subnormal value." Thus the GSH content of sensitive red blood cells is less to begin with, and fans further upon administration of primaquine or some similar drug.
While the haemolitic anemia following drug administration to a sensitive subject is ordinarily of minor concern to the general practitioner, the far greater incidence of drug sensitivity in Negroes must be considered. The protection of Negro troops in malarial areas becomes a complicated matter, since e approximately 10% of them are sensitive to the drug that protects them against malaria.
Moreover, the possible relationship of this primaquine type of drug sensitivity to endemic malaria becomes important to consider. If the drug-sensitive individual already has a reduced oxygen-carrying capacity in the blood, high parasitization for Falciparum malaria may not take place. As with the abnormal hemoglobins, his erythrocytes simply may not maintain the microorganisms at a critical phase in their reproduction. Thus the drug sensitive person may be relatively immune to malaria, and the differential distribution of this trait in individuals of African ancestry may be a clear indication of both where and how the trait arose, as Motulsky (1960) has shown.
Primaquine sensitivity is caused by a deficiency of C6P in the red cell. "It is possible," write Kidson and Corroan (1962) "that a complex interaction of malaria, viral infections, dietary habits and social customs is involved in producing the present pattern of distribution of C-6-PD deficiency, with social customs playing a much more dominant part than has been attributed to them." Allison (1963) replies, "Malaria mar perhaps not be the only factor favoring the enzyme deficiency, but it is an important factor, and no one has yet been able to offer any specific alternative."
Garn, S.M., Human Races, 1965, pp. 89-90.
Further information on racial differences in physiology and disease carne from testing synthetic antimalarials during and especially after World War II. Occasional individuals proved "sensitive" to the antimalarial drugs, that is they developed haemolitic anemia due to the destruction of red blood cells The characteristic symptoms were demonstrable in occasional individuals who had been given primaquine (a quinine-like drug), such common drugs as acetanilid-often used in cold remedies-and the sulfanilamides. A small proportion of individuals maintained on doses of primaquine or acetanilid exhibited drug sensitivity but the vast majority of individuals did not.
When the proportion of drug-sensitive individuals was investigated in different geographical races, interesting results immediately appeared. The incidence of multiple-drug sensitivity in American "whites" proved to be low, 1% or even less. Among 1000 prisoners treated with primaquine and described by Dern, Beutler and Aving ('55) the incidence of sensitivity was 0.1%. However, a larger proportion of American Colored prisoners developed haemolitic anemia following the drug treatment. Among them, proportions of sensitive individual s ranged from 5% in one test to 11% in another group and 12% in yet another group. The true incidence of drug-sensitivity in the American Colored population is therefore close to 10% as shown in the following table.
Studies on the blood of drug-sensitive and drug-insensitive individuals have shown marked differences in the stability of blood cell glutathione. To quote Beutler, Robson and Buttenwieser ('57) "When primaquine was administered to non-sensitive subjects there was no change in the red cell GSH (reduced glutathione) level. When primaquine was administered to a sensitive subject, however, there was an abrupt fall in the GSH content of the red blood cell to about one-half of the original already subnormal value." Thus the GSH content of sensitive red blood cells is less to begin with, and fans further upon administration of primaquine or some similar drug.
While the haemolitic anemia following drug administration to a sensitive subject is ordinarily of minor concern to the general practitioner, the far greater incidence of drug sensitivity in Negroes must be considered. The protection of Negro troops in malarial areas becomes a complicated matter, since e approximately 10% of them are sensitive to the drug that protects them against malaria.
Moreover, the possible relationship of this primaquine type of drug sensitivity to endemic malaria becomes important to consider. If the drug-sensitive individual already has a reduced oxygen-carrying capacity in the blood, high parasitization for Falciparum malaria may not take place. As with the abnormal hemoglobins, his erythrocytes simply may not maintain the microorganisms at a critical phase in their reproduction. Thus the drug sensitive person may be relatively immune to malaria, and the differential distribution of this trait in individuals of African ancestry may be a clear indication of both where and how the trait arose, as Motulsky (1960) has shown.
Primaquine sensitivity is caused by a deficiency of C6P in the red cell. "It is possible," write Kidson and Corroan (1962) "that a complex interaction of malaria, viral infections, dietary habits and social customs is involved in producing the present pattern of distribution of C-6-PD deficiency, with social customs playing a much more dominant part than has been attributed to them." Allison (1963) replies, "Malaria mar perhaps not be the only factor favoring the enzyme deficiency, but it is an important factor, and no one has yet been able to offer any specific alternative."
Garn, S.M., Human Races, 1965, pp. 89-90.
