Primaquine sensitivity

Alving, A. S. et al. (1956). Enzymatic deficiency in primaquine-sensitive erythrocytes. Science, 124, 484-5. 

Bll. Beutler, E., Drug-induced hemolytic anemia (Primaquine sensitivity). In The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), pp, 1031-1067. McGraw-Hill, New York, 1960. 

Distribution of Primaquine-Sensitive Individuals in the Various Population Groups. Primaquine sensitivity was found in Negroes (B7, B19, C3, C7, G6, G7, G18, H21, M7), Caucasians (G18, L3, M7, W3), and certain Jewish tribes (S21, S23). The phenomenon could be detected in 4.6% of an unselected population of 305 North Americans. In healthy Negroes the sensitivity was more common (7.2%) than in Caucasians (1.3%) (G18). In the Jewish population, the defect was found in 20% of the non-Ashkenazic Jews originating from Iraq and Persia, in 5% from Yemen and Turkey, and in 2% from North Africa. Also 3% of the Arabs in Israel showed drug sensitivity. 

In cases of primaquine sensitivity, erythrocytes were shown to be deficient in G-6-PDH activity and thus there is not sufficient NADPH2 for the reduction of GSSG by its reductase system. In such individuals lowered GSH levels in erythrocytes were found (B6, B8, Bll, S8, S24, and others). Furthermore, it can be shown that in these cases, when erythrocytes are incubated with acetylphenylhydrazine (B6, G18), the maintenance of even a lowered GSH level is not possible. The GSH stability test is based on this fact it measures virtually the G-6-PDH activity and not that of GSSGR. 

Finally, the methemoglobin reduction test may be briefly mentioned. The test has been developed for the detection of primaquine sensitivity and depends on the function of the G-6-PDH system. Its principle consists in the oxidation of Hb to MHb by sodium nitrite and the subsequent enzymatic reduction to Hb in presence of methylene blue. The activity of this system can be followed easily by observation of alterations in color after an incubation period or by means of MHb determinations before and after this period (B18). 

B19. Brewer, G. J., Tarlov, A. R., and Kellermeyer, R. W., The hemolytic effect of primaquine. XII. Shortened erythrocyte life span in primaquine sensitive male Negroes in the absence of drug administration. J. Lab. Clin. Med. 58, 217-224 (1961). 

K16. Kirkman, H. N., Glucose-6-phosphate dehydrogenase and human erythrocytes. Characteristics of G-0-P dehydrogenase from normal and primaquine sensitive erythrocytes, Nature 184, 1291 (1959). 

Hematologic effects Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. 

TarlovAR, Brewer GJ, Carson PE, et al. 1962. Primaquine sensitivity Glucose-6-phosphate dehydrogenase deficiency An inborn error of metabolism of medical and biological significance. 

Hemolytic anemia of the primaquine sensitivity type has been induced by nitrofurantoin. The hemolysis appears to be linked to a glucose 6-phosphate dehydrogenase (G-6-PD) deficiency in the red blood cells of affected patients. 

In primaquine-sensitive individuals haemolytic anaemia may occur. There have been four reports on this side effect since 1962 . The daily dose varied between 200 and 800 mg of nitrofurantoin and the duration of treatment ranged from three to fourteen days. In all patients, erythrocyte glucose-6-phosphate dehydrogenase values were reduced. Glutathione blood levels were also found to be depressed . It must be assumed, however, that this side effect, which occurs only in the Negro, is extremely rare and is also reversible. 

Fig. 3-19. Some chemical pathways related to primaquine-sensitive hemolytic anemia. 1 Glucose-6-phosphate dehydrogensase 2 Lac-tonase 3 6-Phosphogluconic dehydrogenase 4 Glutathione reductase...

Kirkman, H. Primaquine sensitivity. In Molecular genetics and human disease (Gardner, L., ed.), p. 106-133. Springfield, Illinois Charles... 

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