Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians

Abstract

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.

Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

“…Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies and shorten the recovery period, particularly, in the absence of specific vaccines or drugs. This would certainly contribute to avoiding CQ and HCQ complications such as acute toxicity, heart failure, and several non-reversible disorders which have been previously reported [ 45 , 50 ]. The results of the current study provide new and strong evidence regarding COVID-19 susceptibility and treatment as a result of the ACE2 polymorphism.…”

The Ototoxicity of Antimalarial Drugs—A State of the Art Review

“…QN was first isolated in 1820 by the French scientists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou (9). CQ was first synthesized in 1934, and hydroxychloroquine sulfate (Plaquenil) was developed in 1946 as a less toxic chloroquine analog (10,11). Another derivative is Mefloquine (Lariam), which was developed by the United States Army in the 1970s and came into use in the mid-1980s.…”

“…Hearing loss is typically bilateral, mild to moderate sensorineural and mostly reversible (10). Many case reports have described ototoxic effects after treatment with antimalarials, especially CQ and HCQ (52); however, this review focuses on studies based on larger groups of patients.…”

Nearly Fatal Hydroxychloroquine Overdose Successfully Treated with Midazolam, Propofol, Sodium Bicarbonate, Norepinephrine, and Intravenous Lipid Emulsion

“…Case Reports in Emergency Medicine lengthening the effective refractory period, and raising the electrical threshold [7,8]. This results in ventricular arrhythmias and cardiogenic shock [5,6].…”