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Quinidine

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

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.

 

Doses -

Horses:

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

 

  Method 2:

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

 

Human-Approved Products:

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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