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quinidine [gluconate (Quinaglute, Quinalan) & sulfate (Quinidex, Quinora)]

Group IA antiarrhythmic. Indications: 1) atrial fibrillation a) chemical cardioversion b) preventing recurrence of atrial fibrillation 2) paroxysmal supraventricular tachycardia (PSVT) 3) ventricular tachycardia - not 1st or 2nd line agent 4) AV junctional contractions 5) Plasmodium falciparum malaria Contraindications: (cautions) 1) avoid IV administration because of quinidine's tendency to cause hypotension 2) avoid in patients with a history of torsades de pointes 3) discontinue use with prolongation of QT interval a) QTc >500 ms b) prolongation of QTc by more than 25% 4) avoid in patients with significant AV block or conduction system disease 5) myasthenia gravis Dosage: Quinidine gluconate. Tradenames: Quinaglute, Quinalan. - 324 mg PO BID/TID. Tabs 324 mg. Quinidine sulfate. Tradenames: Quinidex, Quinora. - 200 mg every 6 hours. Max 2.4 g/day Tabs 200, 300 mg. Sustained release: 300-600 mg PO BID/TID. Tabs 300 mg. Quinidine polygalacturonate. - 275 mg BID/TID. Tabs 275 mg. - parenteral: 1) 400 mg IM every 4-6 hours 2) 200-400 mg IV infused at < 10 mg/min Injection (gluconate): 80 mg/mL (10 mL). Pharmacokinetics: 1) oral bioavailability is 71% 2) some 1st pass hepatic metabolism 3) 87% bound to plasma proteins 4) metabolized by the liver by cyt P450 3A4 to 2 active metabolites 5) 18% of the drug is excreted inchanged in the urine 6) elimination 1/2life is 6 hours - prolonged to 9 hours in patients with cirrhosis 7) therapeutic levels are 2-6 ug/mL Monitor: - serum ALT or serum AST, serum K+ & serum Na+ within 180 days [7] Adverse effects: 1) common (> 10%) - bitter taste, diarrhea (30%), anorexia, nausea/vomiting, epigastric cramping 2) less common (1-10%) - rash, wheezing, blurred vision, lightheadedness, severe headache, tinnitus, hypotension, syncope 3) uncommon (< 1%) - anemia, tachycardia, thrombocytopenic purpura, heart block, ventricular fibrillation, vascular collapse, vertigo, confusion, delirium, fever, angioedema, blood dyscrasias, impaired hearing, respiratory depression 4) other a) proarrhythmic effects - 'quinidine syncope' - QT prolongation - recurrent episodes of torsades de pointes; hypokalemia, hypomagnesemia, severe left ventricular dysfunction predispose to quinidine-induced torsades b) cardiac conduction abnormalities - exacerbation of AV block - SA node exit block - intraventricular conduction block - asystole - in patients with atrial fibrillation/flutter - increase in ventricular rate secondary to decreased atrial rate & vagolytic effects that increase AV conduction c) allergic reactions - fever - rash - hemolytic anemia - thrombocytopenia d) cinchonism (CNS toxicity) - tinnitus - hearing loss - visual disturbances - confusion - delirium - psychosis e) hepatitis f) lupus-like syndrome Drug interactions: 1) serum digoxin levels increase 2-fold with therapeutic levels of quinidine 2) anticoagulant activity of warfarin may be potentiated 3) agents that decrease 1/2life of quinidine a) phenobarbital b) phenytoin c) rifampin d) disopyramide e) nifedipine 4) avoid other agents which prolong the QT interval a) class Ia antiarrhythmics b) class III antiarrhythmics c) phenothiazines d) tricyclic antidepressants e) erythromycin f) terfenadine g) astemizole 5) agents that increase 1/2life of quinidine a) amiodarone b) verapamil c) alkalinizing agents d) cimetidine e) thiazides 6) quinidine enhances effects of non-depolarizing neuromuscular blockers 7) quinidine increases procainamide & N-acetyl procainamide levels 8) quinidine increases propafenone levels by 90% in extensive metabolizers 9) succinylcholine: enhanced neuromuscular blockade 10) quinidine decreases clearance of tricyclic antidepressants 11) bradycardic effect of beta-blockers may be enhanced by quinidine 12) any drug that inhibits cyt P450 3A4 may increase levels of quinidine 13) any drug that induces cyt P450 3A4 may diminish levels of quinidine 14) quinidine strongly inhibits cyt P450 2D6, thus inhibits metabolism of cyt P450 2D6 substrates Laboratory: 1) specimen: a) serum, plasma (EDTA) b) freeze if not assayed within 24 hours c) stable for 1 month at -5 degrees C 2) methods: GLC, HPLC, fluorometry, EIA, FPIA, FIA 3) interferences: a) EIA & FPIA assays do not distinguish quinidine from dihydroquinidine (naturally occuring analog) b) metabolites may cross react in immunoassays c) do NOT use serum separator tubes; separator gel may extract quinidine 4) labs with Loincs - quinidine in specimen - quinidine in body fluid - quinidine in blood - quinidine in serum/plasma - quinidine free in serum/plasma - quinidine in urine Mechanism of action: 1) class IA antiarrhythmic agent 2) slows conduction velocity 3) prolongs effective refractory period 4) decreases automaticity 5) prevents re-entry phenomenon 6) direct anticholinergic effects; decreases vagal tone 7) inhibits cyt P450 2D6 8) inhibitis SLC22A5S

Interactions

drug interactions drug adverse effects of antiarrhythmic agent, Group IA

Related

cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) quinidine in serum/plasma

General

antiarrhythmic agent, Group IA quinoline; leucoline; chinoleine; 1-benazazine; benzo[b]pyridine

Properties

MISC-INFO: elimination route LIVER 80-90% KIDNEY 10-20% 1/2life 4-8 HOURS therapeutic-range 1.3-5 UG/ML toxic-range >6 UG/ML protein-binding 70-80% elimination by hemodialysis + peritoneal dialysis + pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
  3. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 150-51
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  6. Department of Veterans Affairs, VA National Formulary
  7. deprecated reference

Component-of

dextromethorphan/quinidine (Nuedexta)