Q.23 Administration of primaquine causes severe hemolytic anemia because it

(A) increases the demand for NADPH to a level that cells can’t meet

(B) decreases the demand for NADPH

(C) inactivates glutathione peroxidase of erythrocytes

(D) increases reduced glutathione level of erythrocytes

Primaquine administration causes severe hemolytic anemia primarily in individuals with G6PD deficiency due to oxidative stress overwhelming cellular defenses. The correct answer is option (A).​

Option Analysis

Option (A): Primaquine generates reactive oxygen species (ROS) via its metabolites, increasing demand for NADPH to regenerate reduced glutathione (GSH) for antioxidant defense. In G6PD-deficient erythrocytes, NADPH production is impaired, so cells cannot meet this demand, leading to oxidation damage, Heinz bodies, and hemolysis.​

Option (B): Primaquine does not decrease NADPH demand; instead, its oxidative metabolites heighten the need for NADPH to combat ROS.​

Option (C): Primaquine does not directly inactivate glutathione peroxidase; it depletes GSH indirectly through oxidation, and enzyme activity may decline secondarily (~35% in some studies), but this is not the primary cause.​

Option (D): Primaquine decreases reduced glutathione levels by promoting its oxidation to combat ROS, not increases them.​

Introduction: Unraveling Primaquine Hemolytic Anemia and NADPH Demand
Primaquine hemolytic anemia strikes G6PD-deficient patients when the drug’s metabolites spike NADPH demand for antioxidant protection. This oxidative crisis leads to red blood cell destruction, a key concern in malaria treatment and CSIR NET life sciences exams.​

Primaquine Mechanism in Hemolysis

Primaquine treats Plasmodium vivax relapses but its quinone metabolites like 5,6-POQ generate ROS, oxidizing hemoglobin and GSH. G6PD, via the pentose phosphate pathway, supplies NADPH to recycle GSH; deficiency limits this, causing unmet NADPH demand and hemolysis.​

• Older erythrocytes hemolyze first due to lower G6PD activity.​

• Reticulocytosis follows initial hemolysis, conferring resistance.​

G6PD Deficiency Role

G6PD deficiency impairs NADPH production, the sole RBC source, making cells vulnerable to primaquine’s oxidative stress. Variants like Mediterranean cause severe drops in hemoglobin.​

Clinical Implications

Screen for G6PD before primaquine; alternatives exist for deficient patients. Monitor hemoglobin during therapy to catch hemolytic anemia early.​