Treatment of acute chloroquine poisoning

Clemessy, Jean‐Luc; Taboulet, P.; Hoffman, Jerome R.; Hantson, Philippe; Barriot, P.; Bismuth, C; Baud, Frédéric J.

doi:10.1097/00003246-199607000-00021

Cited by 80 publications

(90 citation statements)

References 15 publications

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“…There was no significant difference in gender distribution between patients admitted due to chloroquine poisoning or other drugs. In both cases, more than twice as many females than males were admitted, which is in line with other studies on chloroquine 1,10,16 and pharmaceutical poisoning in general. 4 This observation has been attributed to 'differential gender motivation', with Queen and colleagues 1 as well as other authors in Zimbabwe 4,16 suggesting that chloroquine was used by females as a method of abortion.…”

Section: Discussionsupporting

confidence: 91%

Chloroquine poisoning in Zimbabwe: a toxicoepidemiological study

Ball

Tagwireyi

Nhachi

2002

J of Applied Toxicology

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Chloroquine is commonly implicated in pharmaceutical poisonings in Zimbabwe. A retrospective hospital record review was performed to describe the epidemiology of chloroquine poisoning compared with that of other medicines. All records of admissions to eight referral hospitals in Zimbabwe due to poisoning with single pharmaceutical agents were collated and separated into those involving either chloroquine or other medicines. Case characteristics were compared and a retrospective cohort study performed to investigate the association of pregnancy with chloroquine overdose. Of 544 cases, antimalarials accounted for the largest proportion of admissions (53.1%), with chloroquine accounting for 96.2% (279 cases) of these. The latter were compared with the remaining 265 cases. The median length of hospital stay for the chloroquine group was significantly lower (1 vs 2 days; P = 0.001) and a greater proportion of patients took chloroquine deliberately (80.3% vs 68.7%; P < 0.05). The mortality rate due to chloroquine poisoning was significantly higher than that of poisoning due to other drugs (5.7% vs 0.7%; P < 0.0001). There was no significant gender bias in mortality. Women of childbearing age admitted with chloroquine poisoning (188 cases) were twice as likely to be found pregnant (relative risk = 2.3, 95% CI = 1.2-4.5) than similar women admitted due to other medicines (157 cases). In conclusion, chloroquine is the most common cause of pharmaceutical poisoning admission at referral hospitals in Zimbabwe. It is normally taken deliberately with significant mortality. In women of childbearing age admitted with chloroquine poisoning, pregnancy should be suspected.

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Section: Discussionsupporting

confidence: 91%

Chloroquine poisoning in Zimbabwe: a toxicoepidemiological study

Ball

Tagwireyi

Nhachi

2002

J of Applied Toxicology

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“…Despite its widespread use, chloroquine has a very narrow margin of safety. At therapeutic concentrations, chloroquine causes prolongation of the QT and QRS intervals on the surface electrocardiogram (3,4) and at higher concentrations causes ventricular ectopy and lethal ventricular arrhythmias (5,6). At the cellular level, chloroquine prolongs cardiac action potential duration, enhances automaticity, and reduces the maximum diastolic potential (7)(8)(9).…”

mentioning

confidence: 99%

The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel

Rodríguez-Menchaca

Navarro‐Polanco

Ferrer-Villada

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

124

135

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Although chloroquine remains an important therapeutic agent for treatment of malaria in many parts of the world, its safety margin is very narrow. Chloroquine inhibits the cardiac inward rectifier K ؉ current IK1 and can induce lethal ventricular arrhythmias. In this study, we characterized the biophysical and molecular basis of chloroquine block of Kir2.1 channels that underlie cardiac I K1. The voltage-and K ؉ -dependence of chloroquine block implied that the binding site was located within the ion-conduction pathway. Site-directed mutagenesis revealed the location of the chloroquine-binding site within the cytoplasmic pore domain rather than within the transmembrane pore. Molecular modeling suggested that chloroquine blocks Kir2.1 channels by plugging the cytoplasmic conduction pathway, stabilized by negatively charged and aromatic amino acids within a central pocket. Unlike most ionchannel blockers, chloroquine does not bind within the transmembrane pore and thus can reach its binding site, even while polyamines remain deeper within the channel vestibule. These findings explain how a relatively low-affinity blocker like chloroquine can effectively block I K1 even in the presence of high-affinity endogenous blockers. Moreover, our findings provide the structural framework for the design of safer, alternative compounds that are devoid of Kir2.1-blocking properties.IK1 ͉ ion channel ͉ KCNJ2 ͉ malaria ͉ polyamines

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“…CQ's toxicity is well documented (13,20), yet we observed no concentration-dependent adverse events or severe adverse events. Peak concentrations occur 1 to 6 h after intake of CQ, and severe adverse events usually occur soon after intake of a high dose, suggesting that toxicity is caused by high peak concentrations or a rapid increase in the CQ concentration (3,4,9,12,15). The lack of severe adverse events in this study is probably explained by the use of repeated small doses (6.5 mg kg Ϫ1 dose Ϫ1 ).…”

Section: Vol 53 2009 High-dose Chloroquine In Guinea-bissau 183mentioning

confidence: 65%

Chloroquine Is Grossly Overdosed and Overused but Well Tolerated in Guinea-Bissau

Ursing

Kofoed

Rodrigues

et al. 2009

Antimicrob Agents Chemother

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High chloroquine doses are commonly prescribed in Guinea-Bissau. Double-dose chloroquine has been shown to be more efficacious (92% efficacy) than the standard dose (80% efficacy). However, chloroquine is toxic when overdosed, and it was not known if the high doses prescribed in Guinea-Bissau were taken or whether they caused adverse effects. We aimed to determine the dosage of chloroquine commonly prescribed, the doses commonly taken, and whether concentration-dependent adverse events occurred in routine practice. Chloroquine prescriptions by eight physicians and chloroquine intake by 102 children were recorded. Chloroquine intake and adverse events were assessed by questioning. Chloroquine concentrations in whole blood were measured. The median total chloroquine dose prescribed and that reportedly taken were 81 and 77 mg kg ؊1 , respectively. The total dose was usually split into two to three daily doses of 6.6 mg kg ؊1 each. These were taken unsupervised for a median of 5 days. Forty percent of the study children had chloroquine concentrations in the same range as those found in a previous study in which double the normal dose (50 mg kg ؊1 ) of chloroquine was taken. Only 3/102 children had Plasmodium falciparum in the blood at the time of diagnosis and treatment. No severe adverse events were reported. No adverse events were associated with higher chloroquine concentrations. High doses of chloroquine are commonly taken and well tolerated in Guinea-Bissau. Malaria diagnostics are poor, and chloroquine is commonly prescribed to children without parasitemia. Use of highdose chloroquine is concurrent with an exceptionally low prevalence of chloroquine-resistant P. falciparum.Chloroquine-resistant (CQR) Plasmodium falciparum spread through Africa during the '80s and '90s and was first described in Guinea-Bissau in 1990 (5). Until June 2008, chloroquine (CQ) remained by far the most commonly used antimalarial in the country. In Guinea-Bissau, as in most other areas of Africa, CQR is associated with a mutation in the CQR transporter (pfcrt K76T) (22,25). Despite the presence of the pfcrt K76T mutation and continued CQ use, which should select CQR P. falciparum, the prevalence of CQR P. falciparum is exceptionally low and unchanged in Guinea-Bissau (23).In Guinea-Bissau, treatment with the standard total CQ dose of 25 mg kg Ϫ1 of body weight given over 3 days had an efficacy of 80% (8). Treatment with 50 mg kg Ϫ1 of CQ in two divided daily doses over 3 days resulted in a 92% PCR-corrected efficacy at day 28 (8). When 50 mg kg Ϫ1 was used, 78% of infections with P. falciparum carrying the CQR-associated genetic marker (pfcrt 76T) were successfully treated, while only 34% were successfully treated with 25 mg kg Ϫ1 (22). The WHO recommendation that an antimalarial drug should have a minimum 90% efficacy was therefore still attained with CQ in .CQ is rapidly and almost completely absorbed. The peak concentration is obtained 1 to 3 h after oral intake, and 50 to 65% is protein bound in plasma. The concentration in whole ...

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Treatment of acute chloroquine poisoning

Cited by 80 publications

References 15 publications

Chloroquine poisoning in Zimbabwe: a toxicoepidemiological study

Chloroquine poisoning in Zimbabwe: a toxicoepidemiological study

The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel

Chloroquine Is Grossly Overdosed and Overused but Well Tolerated in Guinea-Bissau

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