Quinidine: class 1a antiarrhythmic from cinchona bark
Quinidine is one of the oldest antiarrhythmics. The substance was isolated from the bark of the South American cinchona tree (Cinchona) in the 19th century and is the D-stereoisomer of quinine. For decades quinidine was a standard for cardioversion and maintenance of sinus rhythm in atrial fibrillation. Today it has been largely replaced by safer antiarrhythmics but retains a place in specific niche indications.
Quinidine is a class 1a antiarrhythmic in the Vaughan Williams classification. The class is characterised by a combination of fast sodium channel inhibition and potassium channel inhibition, which slows conduction and prolongs repolarisation.
Mechanism of action
Quinidine mainly inhibits the activated form of the fast sodium channel. This flattens phase 0 of the action potential and slows conduction in atrium, AV node and ventricle. In addition quinidine inhibits potassium channels (mainly IKr), prolonging repolarisation. The result is a longer QT interval on ECG.
Clinically quinidine is antiarrhythmic by:
- Suppressing ectopic atrial and ventricular activity
- Lengthening the effective refractory period
- Raising the stimulation threshold
- Inhibiting reentry mechanisms
Quinidine also has a vagolytic effect that paradoxically can speed AV conduction. AV-blocking agents such as beta-blockers or verapamil are therefore added before conversion attempts in atrial fibrillation.
Quinidine inhibits CYP2D6, leading to clinically relevant interactions with many psychotropic and cardiac drugs.
Indications
- Brugada syndrome: preferred pharmacotherapy to reduce arrhythmic events, especially in patients with frequent ICD shocks
- Idiopathic ventricular fibrillation: in the rare patients with recurrent episodes
- Short QT syndrome: off-label, as quinidine prolongs the QT interval
- Atrial fibrillation: historically important, now rare because other antiarrhythmics carry fewer risks
- Malaria (combined with quinine): reserve therapy in severe falciparum malaria
- Babesiosis: off-label combined with clindamycin
Dosing and administration
Quinidine sulfate: 200 to 400 mg every 6 hours, maximum 1,600 mg per day. Quinidine gluconate (parenteral): in malaria therapy according to standard protocols.
Brugada syndrome: 600 to 1,000 mg per day, often combined with an ICD.
Take with meals to reduce gastrointestinal complaints. Up-titrate stepwise under ECG monitoring.
Therapeutic monitoring: therapeutic range 2 to 5 mg/L. Levels above 6 mg/L correlate with toxicity (cinchonism, arrhythmias).
ECG controls: regularly, watching the QT interval (cut-off QTc 500 ms or rise above 25 % from baseline).
Side effects
Common: gastrointestinal complaints (diarrhoea in up to 30 %, nausea, vomiting, cramps), cinchonism (tinnitus, headache, drowsiness, visual disturbance, hearing impairment), rash.
Uncommon: hypotension, syncope, thrombocytopenia, haemolytic anaemia, granulomatous hepatitis, lupus-like reaction with arthralgia and positive ANA, photosensitivity.
Rare and very rare: proarrhythmia with torsade de pointes (characteristic complication), AV blocks, asystole, neuroleptic malignant-like syndrome.
Cinchonism: umbrella term for typical poisoning symptoms with tinnitus, hearing impairment, visual disturbance, dizziness, headache and gastrointestinal complaints. Can already occur at therapeutic doses, severe with level overshoot.
Important warnings:
- ECG with QTc, electrolytes, blood count, liver values before therapy
- Correct hypokalaemia and hypomagnesaemia
- Close ECG controls during titration
- Stop therapy if QTc rises above 500 ms or by a clinically meaningful margin
- Syncope or ventricular arrhythmia is a medical emergency
Interactions
Quinidine is both substrate and inhibitor of CYP2D6 and P-glycoprotein, with extensive interactions.
- Digoxin: doubles the digoxin level; halve the dose or monitor
- Other QT-prolonging substances (class III antiarrhythmics, methadone, some antipsychotics, macrolides, fluoroquinolones, antimalarials): additive prolongation, risk of torsade de pointes
- CYP2D6 substrates (codeine, tamoxifen, flecainide, metoprolol, fluoxetine): level changes, enhanced or reduced effect
- Warfarin: enhanced effect, monitor INR
- Cimetidine, ketoconazole: raised quinidine level
- Phenytoin, rifampicin, phenobarbital: accelerated quinidine metabolism
- Diuretics: hypokalaemia increases toxicity
Special considerations
Pregnancy: possible in exceptional indications; in animal studies no clear teratogenicity, human data limited.
Breastfeeding: low transfer to breast milk, individual evaluation.
Contraindications: AV block 2 or 3 without pacemaker, sick sinus syndrome, severe heart failure, recent myocardial infarction with conduction disturbance, long QT or long QT syndrome (except in Brugada syndrome with clear indication), myasthenia gravis, thrombocytopenia after previous quinidine exposure.
Allergic reactions: quinidine can trigger immune phenomena such as lupus-like syndromes, vasculitis and haemolytic anaemia. Stop immediately on suspicion.
High-risk patients: women, the elderly, patients with structural heart disease or electrolyte disturbances are at higher risk for torsade de pointes.
Related substances
- Flecainide, class 1c antiarrhythmic
- Propafenon, another class 1c
- Mexiletin, class 1b
- Chininsulfat, salt form of quinine (related substance)
Frequently asked questions
Why is quinidine rarely used today?
Safer antiarrhythmics and catheter ablation procedures have largely displaced quinidine in classic indications. Risk of torsade de pointes, narrow therapeutic window, gastrointestinal complaints and immune-mediated side effects make it hard to steer. It remains relevant for rare special indications such as Brugada syndrome.
What is cinchonism?
Cinchonism describes the symptoms of cinchona alkaloid poisoning: tinnitus, hearing loss, visual disturbance, dizziness, headache and gastrointestinal complaints. It can already occur at therapeutic doses, especially with level fluctuations.
Does quinidine really help in Brugada syndrome?
Brugada syndrome is based on a dysfunction of cardiac sodium channels. Quinidine has a special property: it markedly inhibits the repolarising Ito current and can normalise the typical Brugada ECG. Clinical data show a reduction in arrhythmic events, which is why quinidine remains standard in this indication.
What checks do I need before and during therapy?
Before starting an ECG with QTc, electrolytes, blood count, liver values and pregnancy test. During therapy regular ECG controls, level measurements and clinical observation for cinchonism. Symptoms such as syncope require immediate evaluation.
Sources
- BfArM Federal Institute for Drugs and Medical Devices
- EMA European Medicines Agency
- AWMF guidelines on cardiac arrhythmias
- Gelbe Liste quinidine monograph
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