Clinical Features and Management of Poisoning due to Antimalarial Drugs

Abstract

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)

A late presentation of ocular quinine toxicity managed with a combination of vasodilatory treatments

“…Symptoms are likely to occur after a single dose of 44 g and death can occur with doses of 8 g. 2 Proposed mechanisms of quinine toxicity include direct toxic damage to neuroretina or ischaemia secondary to arterial vasoconstriction. 3 The resulting generalised vasospasm without alteration of the blood-retinal barrier accounts for the angiographic features seen in Figures 1 and 2.…”

“…Visual recovery with a spherical subjective refraction 6 months after pterygium removal retrospectively proves that irregular hemimeridian 3 astigmatism (with presumably a much flatter cornea on the nasal side) and probably the Descemet's membrane folds themselves were the cause for patient's decreased visual acuity.…”

Clinically Significant Drug Interaction Profiles of Chloroquine Analogues with Adverse Consequences and Risk Management

“…Severe toxic manifestations may occur within 1-3 h and fatal outcomes usually occur within 2-3 h of drug ingestion. The major clinical symptoms are of neurological, respiratory, and cardiovascular toxicity [8,113]; death is usually due to cardiac arrest related to the direct effect of CQ on the myocardium [36]. Overdosage with HCQ has responded to measures similar to those used in the management of CQ overdosage [38].…”

Antimalarial agents: specific chemoprophylaxis regimens

“…It is contraindicated in pregnant women and young children because of its effects on growing bones and teeth (4), it produces vaginitis frequently, and it produces photosensitivity reactions (3). Although proguanil has been used for many years and is thought to be safe (17), most of the previous experience with this drug has been at a lower daily dose (100 rather than 200 mg/day). The efficacy of proguanil appears to vary in different areas of the world.…”