Clinical features and basic mechanisms of quinidine-induced arrhythmias
Key result
Quinidine induces TdP in ~2% of patients, linked to hypokalemia, bradycardia, and early afterdepolarizations.
Why the study?
The lack of correlation between plasma quinidine concentrations and torsade de pointes suggested that external factors such as hypokalemia or unmeasured active metabolites might modulate the electrophysiologic response to quinidine.
Do quinidine and its metabolites induce early afterdepolarizations under conditions of hypokalemia and bradycardia?
Population
Canine Purkinje fibers
Comparison
Alterations in extracellular potassium, stimulation rate, and quinidine metabolites or dihydroquinidine
Design
Experimental electrophysiologic tissue-bath study
Authors
Discussion
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Implication
Quinidine and its metabolites induce early afterdepolarizations in the setting of hypokalemia and bradycardia, providing a mechanistic basis for quinidine-induced torsade de pointes.
Key Points
- To delineate the clinical presentation, predisposing risk factors, and cellular electrophysiological mechanisms underlying proarrhythmic events caused by quinidine.
- Review of clinical records and published literature detailing quinidine cardiotoxicity and ventricular tachydysrhythmias.
- Evaluation of electrophysiological and cellular data focusing on cardiac ion channel blockade and action potential duration changes.
- Quinidine exerts its proarrhythmic effect primarily by blocking delayed rectifier potassium currents, markedly prolonging repolarization and producing early afterdepolarizations.
- Ventricular tachyarrhythmias typically manifest as polymorphic ventricular tachycardia (torsades de pointes), frequently appearing at normal therapeutic or subtherapeutic serum drug levels.
Structured PICO
Do quinidine and its metabolites induce early afterdepolarizations under conditions of hypokalemia and bradycardia?
P
Population
Canine Purkinje fibers (experimental model) and clinical data from patients with quinidine-induced arrhythmias
E
Exposure
Quinidine, dihydroquinidine, and 3-hydroxyquinidine under conditions of lowered extracellular potassium and slowed stimulation rate
O
Outcome
Action potential prolongation and early afterdepolarizationssurrogate
Quinidine and its metabolites induce early afterdepolarizations in the setting of hypokalemia and bradycardia, providing a mechanistic basis for quinidine-induced torsade de pointes.
Cite This Study
Roden et al. (1986) conducted a review in Quinidine-induced arrhythmias (torsade de pointes). Quinidine therapy was evaluated. Quinidine-induced torsade de pointes occurs in 1 to 3% of patients and is associated with hypokalemia, slow heart rates, and early afterdepolarizations.