Generic Name

Quinidine

Mechanism

Quinidine is a Vaughan‑Williams Class Ia anti‑arrhythmic.
* Early‑phase (Phase 0) sodium channel blockade: slows rapid depolarization, reducing conduction velocity.
* Late‑phase (Phase 4) repolarization prolongation: increases action‑potential duration and refractory period, lowering the risk of re‑entrant arrhythmias.
* Increased intracellular calcium via Na⁺/Ca²⁺ exchange inhibition, contributing modestly to its pro‑arrhythmic potential (QT‑interval elongation).

> *High‑yield point:* Quinidine’s potent Na⁺ blockade makes it effective for ventricular arrhythmias but also responsible for its notorious *QT‑prolonging* risk.

Pharmacokinetics

Indications

* Ventricular tachycardia (VT) / Ventricular fibrillation (VF): initial loading dose 500 mg orally (1–2 days) followed by 250–400 mg daily.
* Digoxin toxicity (acute): 500 mg oral loading (occasionally 2 × 250 mg) then 125–250 mg q12h.
* Malaria prophylaxis/therapy (historical; now largely replaced by newer agents).
* Atrial tachycardia/atrial fibrillation in selected cases when β‑blockers or DOACs contraindicated.

> *Clinical pearl:* Since 1998, routine prophylactic use in malaria has waned, but quinidine remains a go‑to antidote for digoxin overdose.

Contraindications

* Absolute:
* Severe left‑bundle‑branch block (LBBB) or right‑bundle‑branch block (RBBB).
* Baseline QTc > 460 ms in men, > 470 ms in women.
* Significant hepatic impairment (Child‑Pugh B–C).
* Relative:
* Age > 65 yrs (increased risk of GI intolerance).
* History of Stevens–Johnson syndrome or drug‑reaction hypersensitivity.
* Pregnancy (Category C).
* Warnings:
* QT‑interval prolongation → torsades de pointes.
* Severe dermatologic reactions (SJS/TEN).
* Hyponatremia (especially in patients on diuretics).
* Interaction with MAO‑i and serotonergic drugs → serotonin syndrome risk.

Dosing

* Oral (first‑day loading): 500 mg q12h for 2–4 days, then 200–400 mg daily.
* *Tip:* Administer with a high‑fat meal to improve absorption, but be mindful of the lag time.
* IV (Grand‑Mother conversion): 5 mg/kg over 30 min (max 2 mg/kg) for acute arrhythmias, followed by infusion at 60 mg/h for hemodynamic stability.
* Digoxin toxicity: 500 mg loading (or 2 × 250 mg) then 125–250 mg q12h.
* Renal impairment: No dose adjustment necessary; monitor serum levels if available.

Adverse Effects

> *Serious risk:* Torsades de pointes is dose‑related; avoid high loading doses and maintain serum drug checks where possible.

Monitoring

* Baseline + serial ECG: QTc, PR interval, QRS duration.
* Daily vitals: HR, BP, SpO₂.
* Laboratory
* Electrolytes (Na⁺, K⁺, Mg²⁺) twice weekly.
* Liver function tests (LFTs) monthly.
* Serum quinidine level (if available) in refractory cases.
* Drug‑interaction screen at initiation and upon any new medication.
* Patient‑education: Report rash, syncope, or palpitations promptly.

Clinical Pearls

1. “Unmasking” vs. “Masking” –
*A single loading dose of quinidine can unmask latent first‑degree AV block or LBBB; subsequent maintenance reduces this risk. Be vigilant when switching patients from Class Ia to β‑blockers.
2. Malaria vs. Digoxin –
*Nycer. While quinidine was historically a malaria mainstay, its therapeutic window is narrower than for digoxin antidote; always weigh the risk‑benefit ratio.
3. QTc‐Monitoring Algorithm –
1. Baseline QTc 480 ms → hold infusion, consider alternative therapy.
4. Food and Timing –
*Food increases absorption but delays it. If strict loading is required (e.g., during VT storm), administer IV first, then transition to high‑fat oral formulation.
5. Cross‑Titration with Other Class Ia Agents –
*When switching from procainamide or disopyramide, use a loading dose of 0.25–0.5 × the maintenance dose to mitigate synergy in QT prolongation.

These pearls help students and clinicians navigate the therapeutic nuances of quinidine, ensuring safe, effective, and evidence‑based patient care.