Quindine

Quindine - General Information

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. Quindine also blocks muscarinic and alpha-adrenergic neurotransmission. [PubChem]

Pharmacology of Quindine

Quindine, a hydantoin anticonvulsant, is used alone or with phenobarbital or other anticonvulsants to manage tonic-clonic seizures, psychomotor seizures, neuropathic pain syndromes including diabetic neuropathy, digitalis-induced cardiac arrhythmias, and cardiac arrhythmias associated with QT-interval prolongation.

Quindine for patients

Before prescribing QUINAGLUTE® as prophylaxis against recurrence of atrial fibrillation, the physician should inform the patient of the risks and benefits to be expected. Discussion should include the facts

• that the goal of therapy will be a reduction (probably not to zero) in the frequency of episodes of atrial fibrillation; and
• that reduced frequency of fibrillatory episodes may be expected, if achieved, to bring symptomatic benefit; but
• that no data are available to show that reduced frequency of fibrillatory episodes will reduce the risks of irreversible harm through stroke or death; and in fact
• that such data as are available suggest that treatment with QUINAGLUTE® is likely to increase the patient's risk of death.

To confirm whether this is the most current prescribing information available on Quinaglute®, or to obtain the most current prescribing information, please call Berlex Laboratories at 1-888-BERLEX-4 (choose option #4, Product Usage Information).

Quindine Interactions

Altered pharmacokinetics of quinidine: diltiazem significantly decreases the clearance and increases the t_1/2 of quinidine, but quinidine does not alter the kinetics of diltiazem. Drugs that alkalinize the urine (carbonic-anhydrase inhibitors, sodium bicarbonate, thiazide diuretics) reduce renal elimination of quinidine.
By pharmacokinetic mechanisms that are not well understood, quinidine levels are increased by coadministration of amiodarone or cimetidine. Very rarely, and again by mechanisms not understood, quinidine levels are decreased by coadministration of nifedipine.
Hepatic elimination of quinidine may be accelerated by coadministration of drugs (phenobarbital, phenytoin, rifampin) that induce production of cytochrome P450IIIA4.
Perhaps because of competition for the P450IIIA4 metabolic pathway, quinidine levels rise when ketaconazole is coadministered.
Coadministration of propranolol usually does not affect quinidine pharmacokinetics, but in some studies the b-blocker appeared to cause increases in the peak serum levels of quinidine, decreases in quinidine's volume of distribution, and decreases in total quinidine clearance. The effects (if any) of coadministration of other b-blockers on quinidine pharmacokinetics have not been adequately studied.
Hepatic clearance of quinidine is significantly reduced during coadministration of verapamil, with corresponding increases in serum levels and half-life.
Altered pharmacokinetics of other drugs: Quinidine slows the elimination of digoxin and simultaneously reduces digoxin's apparent volume of distribution. As a result, serum digoxin levels may be as much as doubled. When quinidine and digoxin are coadministered, digoxin doses usually need to be reduced. Serum levels of digitoxin are also raised when quinidine is coadministered, although the effect appears to be smaller.
By a mechanism that is not understood, quinidine potentiates the anticoagulatory action of warfarin, and the anticoagulant dosage may need to be reduced.
Cytochrome P450IID6 is an enzyme critical to the metabolism of many drugs, notably including mexiletine, some phenothiazines, and most polycyclic antidepressants. Constitutional deficiency of cytochrome P450IID6 is found in less than 1% of Orientals, in about 2% of American blacks, and in about 8% of American whites. Testing with debrisoquine is sometimes used to distinguish the P450IID6-deficient "poor metabolizers" from the majority-phenotype "extensive metabolizers".
When drugs whose metabolism is P450IID6-dependent are given to p.o. metabolizers, the serum levels achieved are higher, sometimes much higher, than the serum levels achieved when identical doses are given to extensive metabolizers. To obtain similar clinical benefit without toxicity, doses given to poor metabolizers may need to be greatly reduced. In the case of prodrugs whose actions are actually mediated by P450IID6-produced metabolites (for example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in poor metabolizers.
Quinidine is not metabolized by cytochrome P450IID6, but therapeutic serum levels of quinidine inhibit the action of cytochrome P450IID6, effectively converting extensive metabolizers into p.o. metabolizers. Caution must be exercised whenever quinidine is prescribed together with drugs metabolized by cytochrome P450IID6.
Perhaps by competing for pathways of renal clearance, coadministration of quinidine causes an increase in serum levels of procainamide.
Serum levels of haloperidol are increased when quinidine is coadministered.
Presumably because both drugs are metabolized by cytochrome P450IIIA4, coadministration of quinidine causes variable slowing of the metabolism of nifedipine. Interactions with other dihydropyridine calcium channel blockers have not been reported, but these agents (including felodipine, nicardipine, and nimodipine) are all dependent upon P450IIIA4 for metabolism, so similar interactions with quinidine should be anticipated.
Altered pharmacodynamics of other drugs: Quinidine's anticholinergic, vasodilating, and negative inotropic actions may be additive to those of other drugs with these effects, and antagonistic to those of drugs with cholinergic, vasoconstricting, and positive inotropic effects. For example, when quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral a-blockade is sometimes reported.
Quinidine potentiates the actions of depolarizing (succinylcholine, decamethonium) and nondepolarizing (d-tubocurarine, pancuronium) neuromuscular blocking agents. These phenomena are not well understood, but they are observed in animal models as well as in humans. In addition, in vitro addition of quinidine to the serum of pregnant women reduces the activity of pseudocholinesterase, an enzyme that is essential to the metabolism of succinylcholine.
Non-interactions of quinidine with other drugs: Quinidine has no clinically significant effect on the pharmacokinetics of diltiazem, flecainide, mephenytoin, metoprolol, propafenone, propranolol, quinine, timolol, or tocainide.
Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, diltiazem, felodipine, omeprazole, or quinine. Quinidine's pharmacokinetics are also unaffected by cigarette smoking.

Quindine Contraindications

Quinidine is contraindicated in patients who are known to be allergic to it, or who have developed thrombocytopenic purpura during prior therapy with quinidine or quinine.
In the absence of a functioning artificial pacemaker, quinidine is also contraindicated in any patient whose cardiac rhythm is dependent upon a junctional or idioventricular pacemaker, including patients in complete atrioventricular block.
Quinidine is also contraindicated in patients who, like those with myasthenia gravis, might be adversely affected by an anticholinergic agent.

Additional information about Quindine

Quindine Indication: For the treatment of ventricular pre-excitation and cardiac dysrhythmias
Mechanism Of Action: Quindine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.
Drug Interactions: Amiloride Amiloride decreases the antiarrhythmic effect of quinidine
Amiodarone Amiodarone increases the effect of quinidine
Amitriptyline Quindine increases the effect of the tricyclic agent
Clomipramine Quindine increases the effect of the tricyclic agent
Nortriptyline Quindine increases the effect of the tricyclic agent
Desipramine Quindine increases the effect of the tricyclic agent
Doxepin Quindine increases the effect of the tricyclic agent
Imipramine Quindine increases the effect of the tricyclic agent
Protriptyline Quindine increases the effect of the tricyclic agent
Trimipramine Quindine increases the effect of the tricyclic agent
Amobarbital The anticonvulsant decreases the effect of quinidine
Aprobarbital The anticonvulsant decreases the effect of quinidine
Butabarbital The anticonvulsant decreases the effect of quinidine
Butalbital The anticonvulsant decreases the effect of quinidine
Butethal The anticonvulsant decreases the effect of quinidine
Dihydroquinidine barbiturate The anticonvulsant decreases the effect of quinidine
Fosphenytoin The anticonvulsant decreases the effect of quinidine
Heptabarbital The anticonvulsant decreases the effect of quinidine
Hexobarbital The anticonvulsant decreases the effect of quinidine
Methohexital The anticonvulsant decreases the effect of quinidine
Methylphenobarbital The anticonvulsant decreases the effect of quinidine
Pentobarbital The anticonvulsant decreases the effect of quinidine
Phenobarbital The anticonvulsant decreases the effect of quinidine
Phenytoin The anticonvulsant decreases the effect of quinidine
Primidone The anticonvulsant decreases the effect of quinidine
Quindine barbiturate The anticonvulsant decreases the effect of quinidine
Secobarbital The anticonvulsant decreases the effect of quinidine
Talbutal The anticonvulsant decreases the effect of quinidine
Anisindione Quinine/quinidine increases the anticoagulant effect
Dicumarol Quinine/quinidine increases the anticoagulant effect
Digoxin Quinine/quinidine increases the effect of digoxin
Digitoxin Quinine/quinidine increases the effect of digoxin
Acenocoumarol Quinine/quinidine increases the anticoagulant effect
Warfarin Quinine/quinidine increases the anticoagulant effect
Aripiprazole Quindine increases the effect and toxicity of aripiprazole
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Cimetidine Cimetidine increases the effect of quinidine
Codeine Quindine decreases the analgesic effect of codeine
Dextromethorphan Quindine increases the toxicity of dextromethorphan
Diltiazem Diltiazem increases the effect and toxicity of quinidine
Nelfinavir Nelfinavir increases the effect and toxicity of quinidine
Nifedipine Decreased quinidine effect, increased nifedipine effect
Posaconazole Contraindicated co-administration
Procainamide Quindine increases the effect of procainamide
Propafenone Quindine increases the effect of propafenone
Quinupristin This combination presents an increased risk of toxicity
Rifampin Rifampin decreases the effect of quinidine
Ritonavir Ritonavir increases the effect and toxicity of quinidine
Verapamil Verapamil increases the effect of quinidine
Atazanavir Increased risk of cardiotoxicity/arrhythmias
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Moxifloxacin Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Ofloxacin Increased risk of cardiotoxicity and arrhythmias
Ranolazine Possible additive effect on QT prolongation
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Telithromycin Increased risk of cardiotoxicity and arrhythmias
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Voriconazole Increased risk of cardiotoxicity and arrhythmias
Ziprasidone Increased risk of cardiotoxicity and arrhythmias
Rivastigmine Possible antagonism of action
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Atracurium The quinine derivative increases the effect of the muscle relaxant
Gallamine Triethiodide The quinine derivative increases the effect of the muscle relaxant
Metocurine The quinine derivative increases the effect of the muscle relaxant
Pancuronium The quinine derivative increases the effect of the muscle relaxant
Succinylcholine The quinine derivative increases the effect of the muscle relaxant
Vecuronium The quinine derivative increases the effect of the muscle relaxant
Itraconazole The imidazole increases the effect and toxicity of quinidine
Ketoconazole The imidazole increases the effect and toxicity of quinidine
Magnesium The antacid increases the effect of quinidine
Salicylate-magnesium The antacid increases the effect of quinidine
Sodium bicarbonate The antacid increases the effect of quinidine
Food Interactions: Not Available
Generic Name: Quinidine
Synonyms: Quinidine Sulfate; Quinidine Gluconate
Drug Category: Antiarrhythmic Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Quinidine: Apo-Quinidine; Biquin Durules; Cardioquin; Chinidin; Cin-Quin; Coccinine; Conchinin; Conchinine; Conquinine; Duraquin; Kinidin; Novoquinidin; Pitayin; Pitayine; Quin-Release; Quinact; Quinaglute; Quinaglute Dura-Tabs; Quinalan; Quinate; Quinatime; Quindine; Quinicardine; Quinidex; Quinidex Extentabs; Quinora;
Absorption: Not Available
Toxicity (Overdose): Not Available
Protein Binding: 80-88%
Biotransformation: Not Available
Half Life: 6-8 hours
Dosage Forms of Quindine: Tablet, extended release Oral
Tablet Oral
Solution Intramuscular
Chemical IUPAC Name: (S)-[(4S,5R,7R)-5-ethenyl-1-azabicyclo[2.2.2]octan-7-yl]-(6-methoxyquinolin-4-yl)methanol
Chemical Formula: C20H24N2O2
Quinidine on Wikipedia: https://en.wikipedia.org/wiki/Quinidine
Organisms Affected: Humans and other mammals