Chemistry - Used as an antiarrhythmic agent, quinidine is an alkaloid obtained from cinchona or related plants, or is prepared from quinine. It is available commercially in three separate salts: gluconate, polygalcturonate, or sulfate. Quinidine gluconate occurs as a very bitter tasting, odorless, white powder. It is freely soluble in water and slightly soluble in alcohol. The injectable form has a pH of 5.5-7. Quinidine polygalcturonate occurs as a bitter tasting, creamy white, amorphous powder. It is sparingly soluble in water and freely soluble in hot 40% alcohol.
Quinidine sulfate occurs as very bitter tasting, odorless, fine, needle-like, white crystals that may cohere 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 a brownish 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 very slowly (1 ml/minute) intravenously. It may be diluted by adding 10 to 40 ml of D5W. Quinidine gluconate is reported to be compatible with bretylium tosylate, cimetidine HCl, and verapamil HCl. It is reportedly incompatible with alkalies and iodides.
Pharmacology - A class IA antiarrhythmic, quinidine has effects similar to that of procainamide. It depresses myocardial excitability, conduction velocity and contractility. Quinidine will prolong the effective refractory period, which prevents the reentry phenomenon and increases conduction times. Quinidine also possesses anticholinergic activity which decreases vagal tone and may facilitate AV conduction.
Uses/Indications - Quinidine is indicated in small animal or equine medicine for the treatment of ventricular 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 - After oral administration, quinidine salts are nearly completely absorbed from the GI. However, the actual amount that reaches the systemic circulation will be reduced due to the hepatic first-pass effect. The extended-release formulations of quinidine sulfate and gluconate, as well as the polygalacturonate tablets, are more slowly absorbed than the conventional tablets or capsules.
Quinidine is distributed rapidly to all body tissues except the brain. Protein binding varies from 82-92%. 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 dose may be excreted unchanged in the urine within 24 hours after dosing. Serum half-lives reported in various species are: horses ≈ 8.1 hours; cattle ≈ 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 of quinidine and decrease its serum half-life.
Contraindications/Precautions - Quinidine is generally contraindicated in patients who have demonstrated previous hypersensitivity reactions to it; myasthenia gravis; complete AV block with an AV junctional or idioventricular pacemaker; intraventricular conduction defects (especially with pronounced QRS widening); digitalis intoxication with associated arrhythmias or AV conduction disorders; aberrant ectopic impulses; or abnormal rhythms secondary to escape mechanisms. It should be used with extreme caution, if at all, in any form of AV block or if any symptoms of digitalis toxicity are exhibited.
Quinidine should be used with caution in patients with uncorrected hypokalemia, hypoxia, and disorders or acid-base balance. Use cautiously in patients with hepatic or renal insufficiency as accumulation of the drug may result.
Adverse Effects/Warnings - In dogs, gastrointestinal effects may include anorexia, vomiting, or diarrhea. Effects related to the cardiovascular system can include weakness, hypotension (especially with too rapid IV administration), negative inotropism, widened QRS complex and QT intervals, AV block, and multiform ventricular tachycardias hypotension.
Horses may exhibit swelling of the nasal mucosa, laminitis, GI distress, and the development of urticarial wheals. Horses may also develop cardiac arrhythmias including AV block, circulatory collapse and sudden death.
Patients exhibiting signs of toxicity or lack of response may be candidates for therapeutic serum monitoring. The therapeutic range is thought to be 2.5 - 5.0 micrograms/ml in dogs. Toxic effects usually 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 and conduction, 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 to remove any unabsorbed drug. IV fluids, plus metaraminol or norepinephrine can be considered to treat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may be used in an attempt to reduce the cardiotoxic effects of quinidine. Forced diuresis using fluids and diuretics along with reduction of urinary pH, may enhance the renal excretion of the drug. Temporary cardiac pacing may be necessary should severe AV block occur. Hemodialysis will effectively remove quinidine, but peritoneal dialysis will not.
Drug Interactions - Digoxin levels may increase considerably in patients stabilized on digoxin who receive quinidine. Some cardiologists recommend decreasing the digoxin dosage by 1/2 when adding quinidine. Therapeutic drug monitoring of both quinidine and digoxin may be warranted in these cases. Coumarin anticoagulants with quinidine may increase the likelihood of bleeding problems developing. Quinidine may increase the neuromuscular blocking effects of drugs like succinylcholine, tubocurarine or atracurium. Phenobarbital, phenytoin or rifampin may induce hepatic enzymes that metabolize quinidine thus reducing quinidine serum half-life by 50%. Cimetidine may increase the effects of quinidine by 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 cardiac contractility (e.g., other antiarrhythmic drugs (procainamide, disopyramide, etc.), phenothiazines). Drugs that alkalinize the urine (carbonic anhydrase inhibitors, thiazide diuretics, sodium bicarbonate, 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 excretion of quinidine and decrease serum levels.
a) Oral Dosing:
Method 1:Give quinidine sulfate powder by stomach tube or in large gelatin capsules.
Day 1: Give 5 gram test dose; if no adverse reactions (see Adverse Effects) may continue therapy
Days 2, 3: 10 gram bid
Days 4, 5: 10 gram tid
Days 6, 7: 10 gram qid
Days 8,9: 10 gram every 5 hours
Day 10 and thereafter: 15 gram qid
Day 1: 5 gram test dose
Day 2: 10 gram every 2 hours until a total dose of 80 grams or less has been given.
Once the arrhythmia is halted, reduce dose total dose by 1/2 every other day until a maintenance dose is reached that prevents recurrence of arrhythmia. If treating atrial fibrillation, quinidine can usually be discontinued 1-2 days after conversion to sinus rhythm. Doses greater than 40 grams per day tend to cause undesirable effects. (Hilwig 1987)
Monitoring Parameters - 1) ECG; 2) Blood pressure if possible, during IV administration; 3) Symptoms of toxicity (see Adverse Reactions/Overdosage); 4) Serum levels. Therapeutic serum levels are believed to range from 2.5 - 5.0 micrograms/ml. Levels greater than 10 micrograms/ml are considered to be toxic.
Client Information - Oral products should be administered at evenly spaced intervals throughout the day/night. GI upset may be decreased if administered with food. Do not allow animal to chew or crush sustained-release oral dosage forms. Notify veterinarian if animal’s condition deteriorates or symptoms of toxicity (e.g., vomiting, diarrhea, weakness, etc.) occur.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Quinidine Sulfate (contains 83% anhydrous quinidine alkaloid) Tablets 200 mg, 300 mg; Quinora® (Key), Generic; (Rx)
Quinidine Sulfate (contains 83% anhydrous quinidine alkaloid) Sustained-Release Tablets 300 mg; Quinidex® Extentabs (Robins); (Rx)
Quinidine Gluconate (contains 62% anhydrous quinidine alkaloid); Sustained-release Tablets 324 mg; Quinaglute® Dura-Tabs (Berlex); Quinalan® (Lannett); Generic; (Rx)
Quinidine Gluconate Injection 80 mg/ml (50 mg/ml of quinidine), 10 ml vials; Generic (Lilly); (Rx)
Quinidine Polygalacturonate (contains 80% anhydrous quinidine alkaloid); Tablets 275 mg; Cardioquin® (Purdue-Frederick); (Rx)
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