Chloroquine overdose

Deaths from chloroquine overdose have been reported with doses as low as 2-3 g in adults, and the death rate is as high as 25%. The effects of chloroquine overdose include cardiac effects (such as dysrhythmias, reduced myocardial contractility, and hypotension) and central nervous system complications (such as confusion, coma, and seizures). 

There have been three reports of chloroquine overdose, two from Oman (40) and one from the Netherlands (41). The two reports from Oman were similar to previously published reports of chloroquine overdose associated with cardiac dysfunction, confusion, and coma both patients had standard treatment with activated charcoal, diazepam infusions, and positive inotropic drugs, and both survived. The single case report from the Netherlands gave pharmacokinetic measurements performed before, during, and after hemoperfusion. This showed that hemoperfusion extracted very little chloroquine and was unlikely to be of any use in chloroquine overdose, as would be expected from the high protein binding and large volume of distribution of chloroquine. 

Overdose with hydroxychloroquine is far less common than with chloroquine. Three of eight patients died (43). Life-threatening symptoms, such as hypotension, conduction disturbances, and hypokalemia can occur within 30 minutes of ingestion and are similar to those seen in chloroquine overdose. The lethal plasma concentration of hydroxychloroquine is not well established. Therapeutic drug concentrations are usually less than... 

Management of hydroxychloroquine overdose is similar to that of chloroquine overdose, including the use of charcoal for drug adsorption, diazepam for seizures and sedation, early intubation and mechanical ventilation, and potassium replacement for severe hjrpokalemia. 

Diazepam is used primarily in the treatment of mental anxiety. In addition, it acts as a muscle relaxant for a variety of medical conditions. It may also be used as a sedative-hypnotic and anticonvulsant (e.g., for status epilepticus and drug-induced seizures). Diazepam may also be used to alleviate some of the symptoms associated with the following cholinesterase poisoning, substance abuse withdrawal, antihistamine overdose. Black Widow spider envenomation, and chloroquine overdose. As an anesthetic, diazepam may be used alone or in combination with other drugs for conscious sedation. 

Chloroquine and other aminoquinolines are used in the prophylaxis or therapy of malaria and other parasitic diseases. Chloroquine and hydroxychloroquine are also used in the treatment of rheumatoid arthritis. Drugs in this class include chloroquine phosphate (Aralen ), amodiaquine hydrochloride (Camoquin ), hydroxychloroquine sulfate (Plaquenil ), mefloquine (Lariam" ), primaquine phosphate, and quinacrine hydrochloride (Atabrine ). Chloroquine overdose is common, especially in countries where malaria is prevalent, and the mortality rate is 10-30%. Quinine toxicity is described on p 326. 

A. Mild to moderate chloroquine overdose results in dizziness, nausea and vomiting, abdominal pain, headache and visual disturbances (sometimes including irreversible blindness), auditory disturbances (sometimes leading to deafness), agitation, and neuromuscular excitability. 

B. Severe chloroquine overdose may cause convulsions, coma, shock, and respiratory or cardiac arrest. Quinidine-like cardiotoxicity may be seen, including sinoatrial arrest, depressed myocardial contractility, QRS or QT interval prolongation, heart block, and ventricular arrhythmias. Severe hypokalemia sometimes occurs and may contribute to arrhythmias. 

Chloroquine is a 4-aminoquinoline used in the treatment and prophylaxis of malaria and hepatic amebiasis, as well as rheumatoid arthritis. Adverse effects are generally less common and less severe. Frequent effects include headache, GI disturbances, and diarrhea. Large doses may cause blurred vision and difficulty focusing. A common adverse effect on the eye is retinopathy. Parenteral therapy with chloroquine can be hazardous, and rapid intravenous injections may result in cardiovascular toxicity. Acute overdose is extremely dangerous death may occur within a few hours. Chloroquine should be used cautiously in patients with liver and kidney impairment. Chloroquine may aggravate the condition of myasthenia... 

Acute overdose may be rapidly fatal without treatment and indeed has even been described as a means of suicide. (Chloroquine may now be bought from pharmacies in the UK without a prescription.) Puhnonciry oedema is followed by convulsions, cardiac arrh5dhmias and coma as little as 50 mg/kg can be fatal. These effects are principally due to the profound negative inotropic action of chloroquine. Diazepam was found fortuitously to protect the heart and adrenaline (epinephrine) reduces intraventricular conduction time this combination of drugs, given by separate i.v. infusions, improves survival. 

Severe hypokalemia after a single large dose of chloroquine has been documented, and some studies show a correlation between plasma potassium concentrations and the severity of the cardiac effects. In a retrospective study of 191 consecutive patients who had taken an overdose of chloroquine (mean blood chloroquine concentration 20 imol/l usual target concentration up to 6 pmol/l), the mean plasma potassium concentration was 3.0 mmolA (0.8) and was significantly lower in those who died than in those who survived (6). Plasma potassium varied directly with the systolic blood pressure and inversely with the QRS and QT intervals. Plasma potassium varied inversely with the blood chloroquine. 

Chloroquine is not used therapeutically in domestic animals. Toxic manifestations of overdose in animals are undefined. 

Symptoms of overdose include nausea, vomiting, transient visual or auditory deficits, drowsiness, and seizures followed by severe cardiac arrhythmias, shock, or cardiorespiratory arrest. Hypotension may be severe and intractable, producing metabolic acidosis and end-organ failure. Cardiac conduction disturbances include complete atrioventricular dissociation, QRS and QT prolongation, severe bradycardia, and ventricular fibrillation. Acute ingestions of 30-50 mg kg of chloroquine in adults and as little as 300 mg in children are potentially fatal. 

Antimalarial unknown mechanism of action. Used for prophylaxis against and treatment of chloroquine-resistant malaria. Tox GI distress, dizziness, seizures in overdose. 

Chloroquine Persisting myasthenic symptoms, including muscular weakness, attributed to prior chloroquine use. Development of myasthenic symptoms in 3 patients, one who took chloroquine in overdose. 4-7... 

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