QUINIDINE GLUCONATE, QUINIDINE POLYGALACTURONATE, QUINIDINE SULFATE
Chemistry - Used as an antiarrhythmic agent, quinidine is an alkaloid obtained from cinchona orrelated plants, or is prepared from quinine. It is available commercially in three separate salts:gluconate, polygalacturonate, or sulfate.
Quinidine gluconate occurs as a very bitter tasting, odorless, white powder. It is freely soluble inwater and slightly soluble in alcohol. The injectable form has a pH of 5.5-7.
Quinidine polygalacturonate occurs as a bitter tasting, creamy white, amorphous powder. It issparingly soluble in water and freely soluble in hot 40% alcohol.
Quinidine sulfate occurs as very bitter tasting, odorless, fine, needle-like, white crystals that maycohere in masses. One gram is soluble in approximately 100 ml of water or 10 ml of alcohol.
Quinidine gluconate injection is usually administered intramuscularly, but may be given veryslowly (1 ml/minute) intravenously. It may be diluted by adding 10 to 40 ml of D5W. Quinidinegluconate is reported to be compatible with bretylium tosylate, cimetidine HCl, and verapamil HCl.
It is reportedly incompatible with alkalies and iodides.
Quinidine also possesses anticholinergic activity which decreases vagal tone and may facilitate AVconduction.
Uses, Indications - Quinidine is indicated in small animal or equine medicine for the treatment ofventricular arrhythmias (VPC's, ventricular tachycardia), refractory supraventricular tachycardias, supraventricular arrhythmias associated with anomalous conduction in Wolff-Parkinson-White(WPW) syndrome, and acute atrial fibrillation. Oral therapy is generally not used in cats.
Quinidine is distributed rapidly to all body tissues except the brain. Protein binding varies from82-92%. The reported volumes of distribution in various species are: horses » 15.1 L/kg, cattle »3.8 L/kg; dogs » 2.9 L/kg; cats » 2.2 L/kg. Quinidine is distributed into milk and crosses the placenta.
Quinidine is metabolized in the liver, primarily by hydroxylation. Approximately 20% of a dosemay be excreted unchanged in the urine within 24 hours after dosing. Serum half-lives reported invarious species are: horses » 8.1 hours; cat le » 2.3 hours; dogs » 5.6 hours; cats » 1.9 hours;swine » 5.5 hours; goats » 0.9 hours. Acidic urine (pH < 6) can increase renal excretion ofquinidine and decrease its serum half-life.
Contraindications/Precautions - Quinidine is generally contraindicated in patients who havedemonstrated previous hypersensitivity reactions to it; myasthenia gravis; complete AV block withan AV junctional or idioventricular pacemaker; intraventricular conduction defects (especially withpronounced QRS widening); digitalis intoxication with associated arrhythmias or AV conductiondisorders; aberrant ectopic impulses; or abnormal rhythms secondary to escape mechanisms. Itshould be used with extreme caution, if at all, in any form of AV block or if any symptoms ofdigitalis toxicity are exhibited.
Quinidine should be used with caution in patients with uncorrected hypokalemia, hypoxia, anddisorders or acid-base balance. Use cautiously in patients with hepatic or renal insufficiency asaccumulation of the drug may result.
Horses may exhibit swelling of the nasal mucosa, laminitis, GI distress, and the development ofurticarial wheals. Horses may also develop cardiac arrhythmias including AV block, circulatorycollapse and sudden death.
Patients exhibiting signs of toxicity or lack of response may be candidates for therapeutic serummonitoring. The therapeutic range is thought to be 2.5 - 5.0 micrograms/ml in dogs. Toxic effectsusually are not seen unless levels are >10 micrograms/ml.
Overdosage - Symptoms of overdosage can include depression, hypotension, lethargy, confusion, seizures, vomiting, diarrhea and oliguria. Cardiac signs may include depressed automaticity andconduction, or tachyarrhythmias. The CNS effects are often delayed after the onset of cardiovascular effects but may persist after the cardiovascular effects have begun to resolve.
If a recent oral ingestion, emptying of the gut and charcoal administration may be beneficial toremove any unabsorbed drug. IV fluids, plus metaraminol or norepinephrine can be considered totreat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may be used in anattempt to reduce the cardiotoxic effects of quinidine. Forced diuresis using fluids and diureticsalong with reduction of urinary pH, may enhance the renal excretion of the drug. Temporary cardiacpacing may be necessary should severe AV block occur. Hemodialysis will effectively removequinidine, but peritoneal dialysis will not.
Coumarin anticoagulants with quinidine may increase the likelihood of bleeding problemsdeveloping.
Quinidine may increase the neuromuscular blocking effects of drugs like succinylcholine, tubocurarine or atracurium.
Phenobarbital, phenytoin or rifampin may induce hepatic enzymes that metabolize quinidinethus reducing quinidine serum half-life by 50%. Cimetidine may increase the effects of quinidineby inhibiting hepatic microsomal enzymes.
Use with caution with other antidysrhythmic agents, as additive cardiotoxic or other toxic effects may result.
Quinidine may antagonize the effects of pyridostigmine, neostigmine, or other anticholinesterases in patients with myasthenia gravis.
Quinidine may potentiate the effects of other drugs having hypotensive effects.
Additive cardiac depressant effects may be seen if used with other agents that depress cardiaccontractility (e.g., other antiarrhythmic drugs (procainamide, disopyramide, etc.), phenothiazines).
Drugs that alkalinize the urine (carbonic anhydrase inhibitors, thiazide diuretics, sodiumbicarbonate, antacids, etc.) may decrease the excretion of quinidine, prolonging its half-life.
Drugs that acidify the urine (e.g., methionine, ammonium chloride) may increase the excretionof quinidine and decrease serum levels.
Quinidine gluconate occurs as a very bitter tasting, odorless, white powder. It is freely soluble inwater and slightly soluble in alcohol. The injectable form has a pH of 5.5-7.
Quinidine polygalacturonate occurs as a bitter tasting, creamy white, amorphous powder. It issparingly soluble in water and freely soluble in hot 40% alcohol.
Quinidine sulfate occurs as very bitter tasting, odorless, fine, needle-like, white crystals that maycohere in masses. One gram is soluble in approximately 100 ml of water or 10 ml of alcohol.
Storage, Stability, Compatibility
All quinidine salts darken upon exposure to light (acquire abrownish tint) and should be stored in light-resistant, well-closed containers. Use only colorless, clear solutions of quinidine gluconate for injection.Quinidine gluconate injection is usually administered intramuscularly, but may be given veryslowly (1 ml/minute) intravenously. It may be diluted by adding 10 to 40 ml of D5W. Quinidinegluconate is reported to be compatible with bretylium tosylate, cimetidine HCl, and verapamil HCl.
It is reportedly incompatible with alkalies and iodides.
Pharmacology - QUINIDINE GLUCONATE, QUINIDINE POLYGALACTURONATE, QUINIDINE SULFATE
A class IA antiarrhythmic, quinidine has effects similar to that of procainamide. Itdepresses myocardial excitability, conduction velocity and contractility. Quinidine will prolong theeffective refractory period, which prevents the reentry phenomenon and increases conduction times.Quinidine also possesses anticholinergic activity which decreases vagal tone and may facilitate AVconduction.
Uses, Indications - Quinidine is indicated in small animal or equine medicine for the treatment ofventricular arrhythmias (VPC's, ventricular tachycardia), refractory supraventricular tachycardias, supraventricular arrhythmias associated with anomalous conduction in Wolff-Parkinson-White(WPW) syndrome, and acute atrial fibrillation. Oral therapy is generally not used in cats.
Pharmacokinetics - QUINIDINE GLUCONATE, QUINIDINE POLYGALACTURONATE, QUINIDINE SULFATE
After oral administration, quinidine salts are nearly completely absorbed fromthe GI. However, the actual amount that reaches the systemic circulation will be reduced due to thehepatic first-pass effect. The extended-release formulations of quinidine sulfate and gluconate, aswell as the polygalacturonate tablets, are more slowly absorbed than the conventional tablets orcapsules.Quinidine is distributed rapidly to all body tissues except the brain. Protein binding varies from82-92%. The reported volumes of distribution in various species are: horses » 15.1 L/kg, cattle »3.8 L/kg; dogs » 2.9 L/kg; cats » 2.2 L/kg. Quinidine is distributed into milk and crosses the placenta.
Quinidine is metabolized in the liver, primarily by hydroxylation. Approximately 20% of a dosemay be excreted unchanged in the urine within 24 hours after dosing. Serum half-lives reported invarious species are: horses » 8.1 hours; cat le » 2.3 hours; dogs » 5.6 hours; cats » 1.9 hours;swine » 5.5 hours; goats » 0.9 hours. Acidic urine (pH < 6) can increase renal excretion ofquinidine and decrease its serum half-life.
Contraindications/Precautions - Quinidine is generally contraindicated in patients who havedemonstrated previous hypersensitivity reactions to it; myasthenia gravis; complete AV block withan AV junctional or idioventricular pacemaker; intraventricular conduction defects (especially withpronounced QRS widening); digitalis intoxication with associated arrhythmias or AV conductiondisorders; aberrant ectopic impulses; or abnormal rhythms secondary to escape mechanisms. Itshould be used with extreme caution, if at all, in any form of AV block or if any symptoms ofdigitalis toxicity are exhibited.
Quinidine should be used with caution in patients with uncorrected hypokalemia, hypoxia, anddisorders or acid-base balance. Use cautiously in patients with hepatic or renal insufficiency asaccumulation of the drug may result.
Adverse Effects, Warnings
In dogs, gastrointestinal effects may include anorexia, vomiting, ordiarrhea. Effects related to the cardiovascular system can include weakness, hypotension (especiallywith too rapid IV administration), negative inotropism, widened QRS complex and QT intervals, AVblock, and multiform ventricular tachycardias hypotension.Horses may exhibit swelling of the nasal mucosa, laminitis, GI distress, and the development ofurticarial wheals. Horses may also develop cardiac arrhythmias including AV block, circulatorycollapse and sudden death.
Patients exhibiting signs of toxicity or lack of response may be candidates for therapeutic serummonitoring. The therapeutic range is thought to be 2.5 - 5.0 micrograms/ml in dogs. Toxic effectsusually are not seen unless levels are >10 micrograms/ml.
Overdosage - Symptoms of overdosage can include depression, hypotension, lethargy, confusion, seizures, vomiting, diarrhea and oliguria. Cardiac signs may include depressed automaticity andconduction, or tachyarrhythmias. The CNS effects are often delayed after the onset of cardiovascular effects but may persist after the cardiovascular effects have begun to resolve.
If a recent oral ingestion, emptying of the gut and charcoal administration may be beneficial toremove any unabsorbed drug. IV fluids, plus metaraminol or norepinephrine can be considered totreat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may be used in anattempt to reduce the cardiotoxic effects of quinidine. Forced diuresis using fluids and diureticsalong with reduction of urinary pH, may enhance the renal excretion of the drug. Temporary cardiacpacing may be necessary should severe AV block occur. Hemodialysis will effectively removequinidine, but peritoneal dialysis will not.
Drug Interactions
Digoxin levels may increase considerably in patients stabilized on digoxinwho receive quinidine. Some cardiologists recommend decreasing the digoxin dosage by 1/2 whenadding quinidine. Therapeutic drug monitoring of both quinidine and digoxin may be warranted inthese cases.Coumarin anticoagulants with quinidine may increase the likelihood of bleeding problemsdeveloping.
Quinidine may increase the neuromuscular blocking effects of drugs like succinylcholine, tubocurarine or atracurium.
Phenobarbital, phenytoin or rifampin may induce hepatic enzymes that metabolize quinidinethus reducing quinidine serum half-life by 50%. Cimetidine may increase the effects of quinidineby inhibiting hepatic microsomal enzymes.
Use with caution with other antidysrhythmic agents, as additive cardiotoxic or other toxic effects may result.
Quinidine may antagonize the effects of pyridostigmine, neostigmine, or other anticholinesterases in patients with myasthenia gravis.
Quinidine may potentiate the effects of other drugs having hypotensive effects.
Additive cardiac depressant effects may be seen if used with other agents that depress cardiaccontractility (e.g., other antiarrhythmic drugs (procainamide, disopyramide, etc.), phenothiazines).
Drugs that alkalinize the urine (carbonic anhydrase inhibitors, thiazide diuretics, sodiumbicarbonate, antacids, etc.) may decrease the excretion of quinidine, prolonging its half-life.
Drugs that acidify the urine (e.g., methionine, ammonium chloride) may increase the excretionof quinidine and decrease serum levels.