Are one or two dangerous? Quinine and quinidine exposure in toddlers.

Quinine and quinidine have been cited as drugs that may cause significant morbidity and mortality in toddlers who ingest one or two pills. The use of both of these drugs has declined in the United States since the 1980s. A review of the literature and Poison Control data reveals that large quinine and quinidine ingestions, although rare in this country, may lead to severe toxicity and death related to cardiovascular and neurological effects in both children and adults. Although the majority of cases of quinine and quinidine toxicity in toddlers occur after ingestions of more than two pills, a single report each of severe toxicity after the equivalent of an ingestion of two pills or less by a toddler exists for both quinine and quinidine. Although the risk to the toddler exposed to one or two tablets seems to be small, triage to an Emergency Department is warranted after quinidine ingestion of any amount and after quinine ingestion that exceeds the age-appropriate therapeutic dose.

Accidental quinidine poisoning in two children.

Two cases of acute accidental quinidine poisioning in two children are presented. Both cases are characterized by the same ECG abnormalities consisting of rhythm disorders and AV and intraventricular conduction defects. It is suggested that there is a causal relationship between the electrophysiologic cardiac effects of quinidine and the ECG abnormalities observed. Both patients were successfully treated by continuous intravenous infusion of a hypertonic sodium chloride solution and lidocaine.

Effect of amiodarone on serum quinidine and procainamide levels.

Serum levels of quinidine or procainamide were measured in patients who had amiodarone added to their antiarrhythmic regimen. Dosages of quinidine or procainamide were held constant. Eleven of 11 patients had an increase in the serum quinidine level, and 11 of 12 other patients had an increase in the serum procainamide level. The dose requirement to maintain a stable plasma level of quinidine or procainamide decreased by 37% and 20%, respectively. Clinical toxicity occasionally occurred with the increase in serum levels of quinidine and procainamide, and the dose of these drugs should be decreased when amiodarone is administered concurrently.

The management of acute quinidine intoxication.

A 16-year-old patient survived severe intoxication with quinidine. Hypotension, rapidly progressing to oliguria and shock, was resistant to the usual therapeutic interventions but responded favorably to the use of an intra-aortic balloon pump. Some hemodynamic implications are discussed. Pulmonary edema occurred and was treated with positive end-expiratory pressure. Electrocardiographic disturbances in conduction, transient bradycardia and recurrent ventricular arrhythmias characterized the initial 36-hour critical period. Unexplained electrolyte abnormalities occurred and further complicated management.

Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide.

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

A death investigation involving quinidine and propranolol.

A death attributed to quinidine-propranolol intoxication is described. Toxicological analysis of the tissues utilized thin layer (TLC) and gas-liquid (GLC) chromatography, ultraviolet (UV) spectrophotometry and gas chromatography-mass spectrometry (GC-MS). Tissue levels for both drugs, along with their chemical ionization mass spectra, are presented.

Hemoperfusion in quinidine intoxication.

A case report on quinidine intoxication is presented. After having ingested 8.1 g quinidine the patient had clinical and ECG signs of a severe intoxication and a serum quinidine level of 8.5 mg 1. She was treated for six hours with charcoal hemoperfusion. Serum quinidine was on an average 36% lower after than before the cartridge. The mean quinidine clearance of hemoperfusion was 24 ml/min. All clinical and ECG signs of quinidine intoxication were normalized during hemoperfusion. The data justify that hemoperfusion is probably the best way to treat severe quinidine intoxication.

Elimination kinetic of high polar metabolites pool of quinidine from human serum.

The elimination half-life of high polar metabolites pool of quinidine (t1/2 beta = 6.1 h) has been determined in a quinidine phenobarbiturate intoxicated patient after the complete elimination of quinidine (its precursor) from blood. It is equivalent to the generally accepted t1/2 beta of quinidine (6.1 +/- 1.8 h) but substantially different from the t1/2 beta "hybrid" of 3-hydroxyquinidine (10.0 h) determined in therapeutic conditions in which 3-hydroxyquinidine coexists with quinidine in blood. With regard to the low serum level of quinidine and strong ECG impairments, it is speculated that high polar metabolites of quinidine taken as a whole could be involved in this life threatening intoxication.