The risk of antimalarials in patients with renal failure

Thorogood, Natasha; Atwal, Sangeeta; Mills, William R.; Jenner, Mark A.; Lewis, Deborah; Cavenagh, Jamie; Agrawal, Sanjay

doi:10.1136/pgmj.2007.063735

Cited by 15 publications

(8 citation statements)

References 6 publications

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“…It is therefore recommended that doses should be lowered in patients with renal impairment (36). Thus it is no surprise that it is not recommended for patients with a GFR of 10 -20 ml/min to take chloroquine Ͼ50 mg per day (36).…”

Section: Discussionmentioning

confidence: 99%

Chronic use of chloroquine disrupts the urine concentration mechanism by lowering cAMP levels in the inner medulla

Bergen

Blount

2012

American Journal of Physiology-Renal Physiology

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Chloroquine, a widely used anti-malaria drug, has gained popularity for the treatment of rheumatoid arthritis, systemic lupus erythematosus (SLE), and human immunodeficiency virus (HIV). Unfortunately, chloroquine may also negatively impact renal function for patients whose fluid and electrolyte homeostasis is already compromised by diseases. Chronic administration of chloroquine also results in polyuria, which may be explained by suppression of the antidiuretic response of vasopressin. Several of the transporters responsible for concentrating urine are vasopressin-sensitive including the urea transporters UT-A1 and UT-A3, the water channel aquaporin-2 (AQP2), and the Na+-K+-2Cl−cotransporter (NKCC2). To examine the effect of chloroquine on these transporters, Sprague-Dawley rats received daily subcutaneous injections of 80 mg·kg−1·day−1of chloroquine for 4 days. Twenty-four hour urine output was twofold higher, and urine osmolality was decreased by twofold in chloroquine-treated rats compared with controls. Urine analysis of treated rats detected the presence chloroquine as well as decreased urine urea and cAMP levels compared with control rats. Western blot analysis showed a downregulation of AQP2 and NKCC2 transporters; however, UT-A1 and UT-A3 abundances were unaffected by chloroquine treatment. Immunohistochemistry showed a marked reduction of UT-A1 and AQP2 in the apical membrane in inner medullary collecting ducts of chloroquine-treated rats. In conclusion, chloroquine-induced polyuria likely occurs as a result of lowered cAMP production. These findings suggest that chronic chloroquine treatment would exacerbate the already compromised fluid homeostasis observed in diseases like chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Chronic use of chloroquine disrupts the urine concentration mechanism by lowering cAMP levels in the inner medulla

Bergen

Blount

2012

American Journal of Physiology-Renal Physiology

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“…When using 3% NaCl, a bolus of 2–4 mEq/kg may be considered, and sodium levels should be closely monitored [ 111 ]. Approximately 50% of chloroquine is excreted renally, and acute renal failure is possible following acute intoxication [ 112 ]. Providers should anticipate the possibility of extended toxicity course in patients with acute and/or chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

“…Providers should anticipate the possibility of extended toxicity course in patients with acute and/or chronic renal failure. Unfortunately, hemodialysis use has been reported as ineffective due to high protein binding and large volume of distribution intrinsic to the aminoquinolines [ 112 ]. Case report evidence suggests hemodialysis efficacy can be augmented by use of ILE [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians

Porta

Bornstein

Coye

et al. 2020

The American Journal of Emergency Medicine

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Background Acute chloroquine and hydroxychloroquine toxicity is characterized by a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias and is associated with significant morbidity and mortality. Objective This review describes acute chloroquine and hydroxychloroquine toxicity, outlines the complex pathophysiologic derangements, and addresses the emergency department (ED) management of this patient population. Discussion Chloroquine and hydroxychloroquine are aminoquinoline derivatives widely used in the treatment of rheumatologic diseases including systemic lupus erythematosus and rheumatoid arthritis as well as for malaria prophylaxis. In early 2020, anecdotal reports and preliminary data suggested utility of hydroxychloroquine in attenuating viral loads and symptoms in patients with SARS-CoV-2 infection. Aminoquinoline drugs pose unique and significant toxicological risks, both during their intended use as well as in unsupervised settings by laypersons. The therapeutic range for chloroquine is narrow. Acute severe toxicity is associated with 10–30% mortality owing to a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias. Treatment in the ED is focused on decontamination, stabilization of cardiac dysrhythmias, hemodynamic support, electrolyte correction, and seizure prevention. Conclusions An understanding of the pathophysiology of acute chloroquine and hydroxychloroquine toxicity and available emergency treatments can assist emergency clinicians in reducing the immediate morbidity and mortality associated with this disease.

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“…74 Plasma HCQ levels should be measured in patients with severely compromised function, and the dose adjusted accordingly. CQ should be reduced to no more than 50 mg once daily in patients with a glomerular filtration rate (GFR) of 10 to 20 mL/min; further, it is contraindicated in patients with a GFR of less than 10 mL/min.…”

Section: Gastrointestinal Adverse Effectsmentioning

confidence: 99%