quinidine [gluconate (Quinaglute, Quinalan) & sulfate (Quinidex, Quinora)]
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Introduction
Indications
- atrial fibrillation
- chemical cardioversion
- preventing recurrence of atrial fibrillation
- paroxysmal supraventricular tachycardia (PSVT)
- ventricular tachycardia
- not 1st or 2nd line agent
- AV junctional contractions
- Plasmodium falciparum malaria
Contraindications
(cautions)
- avoid IV administration because of quinidine's tendency to cause hypotension
- avoid in patients with a history of torsades de pointes
- discontinue use with prolongation of QT interval
- avoid in patients with significant AV block or conduction system disease
- myasthenia gravis
Dosage
Quinidine gluconate. Tradenames: Quinaglute, Quinalan.
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:
- 400 mg IM every 4-6 hours
- 200-400 mg IV infused at < 10 mg/min Injection (gluconate): 80 mg/mL (10 mL).
Pharmacokinetics
- oral bioavailability is 71%
- some 1st pass hepatic metabolism
- 87% bound to plasma proteins
- metabolized by the liver by cyt P450 3A4 to 2 active metabolites
- 18% of the drug is excreted inchanged in the urine
- elimination 1/2life is 6 hours
- prolonged to 9 hours in patients with cirrhosis
- therapeutic levels are 2-6 ug/mL
elimination via liver
elimination via kidney
1/2life = 4-8 hours
protein binding = 70-80 %
elimination by hemodialysis = +
elimination by peritoneal dialysis = +
Monitor
Adverse effects
- common (> 10%)
- less common (1-10%)
- rash, wheezing, blurred vision, lightheadedness, severe headache, tinnitus, hypotension, syncope
- uncommon (< 1%)
- anemia, tachycardia, thrombocytopenic purpura, heart block, ventricular fibrillation, vascular collapse, vertigo, confusion, delirium, fever, angioedema, blood dyscrasias, impaired hearing, respiratory depression
- other
- proarrhythmic effects
- 'quinidine syncope'
- QT prolongation
- recurrent episodes of torsades de pointes; hypokalemia, hypomagnesemia, severe left ventricular dysfunction predispose to quinidine-induced torsades
- QT prolongation
- 'quinidine syncope'
- 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
- allergic reactions
- cinchonism (CNS toxicity)
- hepatitis
- lupus-like syndrome
- proarrhythmic effects
Drug interactions
- serum digoxin levels increase 2-fold with therapeutic levels of quinidine
- anticoagulant activity of warfarin may be potentiated
- agents that decrease 1/2life of quinidine
- avoid other agents which prolong the QT interval
- agents that increase 1/2life of quinidine
- quinidine enhances effects of non-depolarizing neuromuscular blockers
- quinidine increases procainamide & N-acetyl procainamide levels
- quinidine increases propafenone levels by 90% in extensive metabolizers
- succinylcholine: enhanced neuromuscular blockade
- quinidine decreases clearance of tricyclic antidepressants
- bradycardic effect of beta-blockers may be enhanced by quinidine
- any drug that inhibits cyt P450 3A4 may increase levels of quinidine
- any drug that induces cyt P450 3A4 may diminish levels of quinidine
- quinidine strongly inhibits cyt P450 2D6, thus inhibits metabolism of cyt P450 2D6 substrates
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of beta-adrenergic receptor antagonists with quinidine
Laboratory
- specimen:
- methods: GLC, HPLC, fluorometry, EIA, FPIA, FIA
- interferences:
- EIA & FPIA assays do not distinguish quinidine from dihydroquinidine (naturally occuring analog)
- metabolites may cross react in immunoassays
- do NOT use serum separator tubes; separator gel may extract quinidine
- labs with Loincs
Mechanism of action
- class IA antiarrhythmic agent
- slows conduction velocity
- prolongs effective refractory period
- decreases automaticity
- prevents re-entry phenomenon
- direct anticholinergic effects; decreases vagal tone
- inhibits cyt P450 2D6
- inhibitis SLC22A5S
More general terms
Additional terms
- 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
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 150-51
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ 7.0 7.1 deprecated reference
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11069
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5953
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5320867
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=441074
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3000825
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5008
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=64669