Jaeger A, Sauder P, Kopferschmitt J, Flesch F
Med Toxicol Adverse Drug Exp. 1987 Jul-Aug;2(4):242-73. doi: 10.1007/BF03259868.
The toxicities of antimalarial drugs vary because of the differences in the chemical structures of these compounds. Quinine, the oldest antimalarial, has been used for 300 years. Of the 200 to 300 compounds synthesised since the first synthetic antimalarial, primaquine in 1926, 15 to 20 are currently used for malaria treatment, most of which are quinoline derivatives. Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias. Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose. Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concentrations and clinical features, and confirmed the inefficacy of haemodialysis, haemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis. The main feature of primaquine overdose is methaemoglobinaemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes. The main feature of dapsone poisoning is severe methaemoglobinaemia which is related to dapsone and to its metabolites. Recent toxicokinetic studies confirmed the efficacy of oral activated charcoal, haemodialysis and haemoperfusion in enhancing removal of dapsone and its metabolites. No overdose has been reported with artemesinine, a new antimalarial tested in the People's Republic of China. The general management of antimalarial overdose include gastric lavage and symptomatic treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
抗疟药物的毒性各不相同，因为这些化合物的化学结构存在差异。奎宁是最古老的抗疟药，已使用了300年。自1926年第一种合成抗疟药伯氨喹问世以来，合成的200至300种化合物中，目前有15至20种用于疟疾治疗，其中大多数是喹啉衍生物。喹啉衍生物，特别是奎宁和氯喹，过量使用时毒性很大。其毒性作用与其对心脏的奎尼丁样作用有关，包括循环骤停、心源性休克、传导障碍和室性心律失常。其他临床特征包括意识模糊、昏迷、惊厥、呼吸抑制。失明是奎宁过量使用时常见的并发症。严重氯喹中毒时始终存在低钾血症，尽管显然可自行纠正，且是严重程度的良好指标。最近对奎宁和氯喹的毒代动力学研究表明，摄入剂量、血清浓度与临床特征之间存在良好的相关性，并证实血液透析、血液灌流和腹膜透析对促进药物清除无效。其他喹啉衍生物的毒性似乎较小。阿莫地喹可能会引起诸如胃肠道症状、粒细胞缺乏症和肝炎等副作用。伯氨喹过量使用的主要特征是高铁血红蛋白血症。尚未有甲氟喹和哌喹过量使用的病例报告。吖啶衍生物阿的平过量使用可能导致恶心、呕吐、意识模糊、惊厥和急性精神病。用于疟疾治疗的二氢叶酸还原酶抑制剂有磺胺多辛、氨苯砜、氯胍、甲氧苄啶和乙胺嘧啶。这些药物大多联合使用。氯胍是最安全的抗疟药之一。乙胺嘧啶过量使用时曾有惊厥、昏迷和失明的报告。磺胺多辛可诱发中毒性表皮坏死松解症和史蒂文斯－约翰逊综合征。氨苯砜中毒的主要特征是严重的高铁血红蛋白血症，这与氨苯砜及其代谢产物有关。最近的毒代动力学研究证实，口服活性炭、血液透析和血液灌流对促进氨苯砜及其代谢产物的清除有效。在中国进行试验的新型抗疟药青蒿素尚未有过量使用的报告。抗疟药过量的一般处理包括洗胃和对症治疗。（摘要截选至400词）
