Drug information of Quinidine

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Quinidine

فارسی

Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with class 1a activity. ; it is an optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.

Mechanism of effect

Class Ia antiarrhythmic agent; depresses phase 0 of the action potential; decreases myocardial excitability and conduction velocity, and myocardial contractility by decreasing sodium influx during depolarization and potassium efflux in repolarization; also reduces calcium transport across cell membrane

Pharmacodynamic

Distribution: Vd: Adults: 2 to 3 L/kg, decreased with congestive heart failure (0.5 L/kg), malaria; increased with cirrhosis.

Pharmacokinetics

  • Protein binding: Newborns: 50% to 70%; Adults: 80% to 88%
  • Binds mainly to alpha 1-acid glycoprotein and to a lesser extent albumin
  • Metabolism: Extensively hepatic (50% to 90%) to inactive compounds
  • Bioavailability: Sulfate: ~70% with wide variability between patients (45% to 100%); Gluconate: 70% to 80%
  • Half-life elimination, plasma: Children: 2.5 to 6.7 hours ; Adults: 6 to 8 hours; prolonged with elderly, cirrhosis, and congestive heart failure
  • Excretion: Urine (15% to 25% as unchanged drug)

Drug indications

malaria

Dosage

Dosage Forms & Strengths

tablet

200mg (as sulfate)

300mg (as sulfate)

tablet, extended-release

300mg (as sulfate)

324mg (as gluconate)

injectable solution

80mg/mL (as gluconate)

Arrhythmias

Quinidine Sulfate

Test Dose: 200 mg PO quinidine sulfate several hr before full dosage

AFib: 300-400 mg PO q6hr

PSVT: 400-600 mg PO q2-3hr until paroxysm terminated

Atrial/Ventricular Premature Contractions: 200-300 mg PO q6-8hr

Maint: 200-400 mg PO q6-8hr or 600 mg of SR PO q8-12hr

No more than 3-4 g/day

Quinidine Gluconate

324-660 mg PO q8-12hr

Maintenance: 648 mg PO q12hr OR 324-660 mg PO q8hr

PSVT: 400 - 600 mg PO q2-3hr until paroxysm is terminated

IV: Usual <5 mg/kg (but may need up to 10 mg/kg) at 0.25 mg/kg/min

Malaria

Quinidine Gluconate

Regimen I

Load: 24 mg/kg diluted in 250 mL NS IV infusion over 4 hours  

Maintenance: Follow by 12 mg/kg IV infusion over 4 hours q8hr beginning 8 hr after initiation of loading dose except in patients able to swallow the same doses of quinidine are administered using 300 mg quinidine sulfate tablets

Regimen II

Load: 10 mg/kg diluted in 5 mL/kg NS IV over 1-2 hr 

Maintenance: Follow by 0.02 mg/kg/min continuous IV infusion; in patients able to swallow oral quinine is administered every 8 hr to give as much quinine as patient received in quinidine q8hr

PO regimen: 300 mg quinidine or 650 mg quinine PO q8hr for 3 days (Africa and South America) or 7 days (Southeast Asia) or until parasitemia is reduced to 1%

Renal Impairment

CrCl < 10 mL/min: Administer 75% of normal dose

CrCl ≥10 L/min: Dose adjustment not necessary

Hepatic Impairment

Not studied

Alerts

Concerns related to adverse effects:

Hepatotoxicity: Has been associated with severe hepatotoxic reactions, including granulomatous hepatitis.

Hypersensitivity reactions: With use, hypersensitivity reactions may occur.

Proarrhythmic effects: Monitor for proarrhythmic effects; may cause QT prolongation and subsequent torsade de pointes. Monitor and adjust dose to prevent QTc prolongation. Avoid use in patients with diagnosed or suspected congenital long QT syndrome.

Disease-related concerns:

  • Arrhythmias: Appropriate use: Antiarrhythmic drugs have not been shown to enhance survival in non-life-threatening ventricular arrhythmias and may increase mortality; the risk is greatest with structural heart disease. Quinidine may increase mortality in treatment of atrial fibrillation/flutter.
  • Atrial fibrillation/flutter: May increase ventricular response rate in patients with atrial fibrillation or flutter; control AV conduction before initiating.
  • Conduction disturbances: Use with caution in patients at risk for heart block; can unmask sick sinus syndrome (causes bradycardia).
  • Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.
  • G6PD deficiency: Hemolysis may occur in patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency.
  • Left ventricular dysfunction/heart failure (HF): Use with caution in patients with reduced left ventricular ejection fraction; may precipitate or exacerbate condition.
  • Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dosage recommended.

Concurrent drug therapy issues:

Antiarrhythmics: Use with caution with concurrent use of other antiarrhythmics.

Digoxin: Use may cause digoxin-induced toxicity; adjust digoxin's dose.

Dosage form specific issues:

Different salts: Do not interchange the different salt products.

Points of recommendation

Overly rapid infusion of Quinidine may cause peripheral vascular collapse and severe hypotension.

In patients without implanted pacemakers who are at high risk of complete atrioventricular block, Quinidine should be used only with caution.

By a mechanism that is not understood, Quinidine potentiates the anticoagulatory action of warfarin, and the anticoagulant dosage may need to be reduced.

Pregnancy level

C

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