Chloroquine is used for the treatment of uncomplicated malaria and extra-intestinal amebiasis. Malaria is caused by infection of parasites. Chloroquine is active against the erythrocytic forms of susceptible strains of , , , and . Chloroquine is not active against the gametocytes and the exoerythrocytic forms including the hypnozoite stage ( and ) of the parasites. Additionally, resistance to chloroquine and hydroxychloroquine has been reported in species, thus chloroquine therapy is not indicated if the infection arose in a region with known resistance. Chloroquine is used in first-line treatment of malaria with primaquine. Studies have indicated chloroquine is effective against the trophozoites of , which causes amebic dysentery, or amebiasis. (1) Chloroquine also has off-label uses for treatment of rheumatic diseases and has been investigated as a potential antiviral therapy as well as an adjuvant chemotherapy for several types of cancer. (2, 3, 4, 5) Chloroquine accumulates in cellular acidic compartments such as the parasitic food vacuole and mammalian lysosomes, leading to alkalinization of these structures. This change in pH can impair the action of enzymes responsible for the formation of hemozoin by the parasite from ingestion of the host’s hemoglobin; this reaction occurs in the parasitic vacuole (6). Thus, chloroquine targets the blood-stage of the malaria parasites but cannot eliminate dormant hypnozoites and must be administered with a drug that targets the dormant parasitic form (1). Chloroquine, developed in the 1940s, has been superseded as the first-line recommended antimalarial therapy by both the US Centers for Disease Control (CDC) and World Health Organization (WHO), with the exceptions of during the first trimester of pregnancy or for malarial prophylaxis of a pregnant individual who is also deficient for glucose-6-phosphate dehydrogenase (G6PD) (7, 8). Among antimalarial medications, chloroquine is less likely than other medicines to cause hemolysis in G6PD-deficient individuals; however, the FDA-approved drug label states there is still a risk of hemolysis (Table 1) (1). In contrast, the Clinical Pharmacogenetics Implementation Consortium (CPIC) performed a systematic review of the available clinical literature and found low-to-no risk of acute hemolytic anemia for individuals with G6PD deficiency who take hydroxychloroquine or chloroquine (9) (Table 2). It should be noted that G6PD deficiency has a range of severity; CPIC advises caution for all medications when used by an individual with a severe G6PD deficiency with chronic non-spherocytic hemolytic anemia (CNSHA).
氯喹用于治疗非复杂性疟疾和肠外阿米巴病。疟疾由寄生虫感染引起。氯喹对恶性疟原虫、间日疟原虫、卵形疟原虫和三日疟原虫敏感株的红细胞内期具有活性。氯喹对疟原虫的配子体和包括休眠子阶段（间日疟原虫和卵形疟原虫）在内的红细胞外期无活性。此外，已有报道恶性疟原虫对氯喹和羟氯喹耐药，因此，如果感染发生在已知有耐药性的地区，则不建议使用氯喹治疗。氯喹与伯氨喹联合用于间日疟的一线治疗。研究表明氯喹对引起阿米巴痢疾或阿米巴病的溶组织内阿米巴滋养体有效。（1）氯喹还有治疗风湿性疾病的非适应证用药，并且已被研究作为一种潜在的抗病毒疗法以及几种癌症的辅助化疗药物。（2,3,4,5）氯喹在细胞酸性区室如寄生食物泡和哺乳动物溶酶体中蓄积，导致这些结构碱化。这种pH值的变化会损害寄生虫摄取宿主血红蛋白后负责形成疟原虫色素的酶的活性；这种反应发生在寄生泡中（6）。因此，氯喹作用于疟原虫的血液阶段，但不能消除休眠的休眠子，必须与作用于休眠寄生形式的药物联合使用（1）。氯喹于20世纪40年代研发，除妊娠头三个月或用于预防同时缺乏葡萄糖-6-磷酸脱氢酶（G6PD）的孕妇疟疾外，已被美国疾病控制中心（CDC）和世界卫生组织（WHO）取代为一线推荐抗疟治疗药物（7,8）。在抗疟药物中，氯喹比其他药物在G6PD缺乏个体中引起溶血的可能性更小；然而，美国食品药品监督管理局（FDA）批准的药品标签表明仍有溶血风险（表1）（1）。相比之下，临床药物遗传学实施联盟（CPIC）对现有临床文献进行了系统评价，发现服用羟氯喹或氯喹的G6PD缺乏个体发生急性溶血性贫血的风险较低或无风险（9）（表2）。应当指出，G6PD缺乏有一系列严重程度；CPIC建议严重G6PD缺乏伴慢性非球形细胞溶血性贫血（CNSHA）的个体使用所有药物时都应谨慎。
