PROCAINAMIDE HCL
Chemistry - Structurally related to procaine, procainamide is used as an antiarrhythmic agent.
Procainamide HCl differs from procaine by the substitution of an amide group for the ester groupfound on procaine. It occurs as an odorless, white to tan, hygroscopic, crystalline powder with apKa of 9.23 and a melting range from 165°-169°C. It is very soluble in water and soluble in alcohol. The pH of the injectable product ranges from 4 - 6.
The injectable product is reportedly compatible with sodium chloride 0.9% injection, and waterfor injection. Procainamide is also compatible with dobutamine HCl, lidocaine HCl, and verapamil
HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluentsused. It is suggested to consult specialized references for more specific information (e.g.,
Handbook on Injectable Drugs by Trissel; see bibliography).
On ECG, QRS widening, and prolonged PR & QT intervals can be seen. The QRS complex and T wave may occasionally show some slight decreases in voltage.
Uses, Indications - Procainamide is indicated for the treatment of ventricular premature complexes(VPC's), ventricular tachycardia, or supraventricular tachycardia associated with Wolff-Parkinson-White (WPW) syndrome with wide QRS complexes. Higher doses may be beneficial in thetreatment of supraventricular tachycardias, although procainamide cannot be considered a first-lineagent for this dysrhythmia.
After oral administration in humans, approximately 75-95% of a dose is absorbed in the intestine, but some patients absorb less than 50% of a dose. Food, delayed gastric emptying or decreasedstomach pH may delay oral absorption. In dogs, it has been reported that the oral bioavailability isapproximately 85% and the absorption half-life is 0.5 hours. However, there is an apparent largedegree of variability in both bioavailability and half-life of absorption.
Distribution of procainamide is highest into the CSF, liver, spleen, kidneys, lungs, heart andmuscles. The volume of distribution in dogs is approximately 1.4 - 3 L/kg. It is only approximately20% protein bound in humans and 15% in dogs. Procainamide can cross the placenta and isexcreted into milk.
The elimination half-life in dogs has been reported to be variable, most studies report valuesbetween 2-3 hours. In humans, procainamide is metabolized to N-acetyl-procainamide (NAPA), anactive metabolite. It appears, however, that dogs do not form appreciable amounts of NAPA fromprocainamide. In the dog, approximately 90% (50-70% unchanged) of an intravenous dose isexcreted in the urine as procainamide and metabolites within 24 hours after dosing.
Contraindications/Precautions - Procainamide may be contraindicated in patients with myasthenia gravis (see Drug Interactions). Procainamide is contraindicated in patients hypersensitive toit, procaine or other chemically related drugs. In humans, procainamide is contraindicated in patientswith systemic lupus erythematosis (SLE), but it is unknown if it adversely affects dogs with thiscondition. Procainamide should not be used in patients with torsade de pointes, or with 2nd or 3rddegree heart block (unless artificially paced).
Procainamide should be used with extreme caution, if at all, in patients with cardiac glycosideintoxication. It should be used with caution in patients with significant hepatic or renal disease orwith congestive heart failure.
Gastrointestinal effects may include anorexia, vomiting, or diarrhea. Effects related to thecardiovascular system can include weakness, hypotension, negative inotropism, widened QRScomplex and QT intervals, AV block, multiform ventricular tachycardias. Fevers and leukopeniasare a possibility. Profound hypotension can occur if injected too rapidly IV. In humans, an SLEsyndrome can occur, but its incidence has not been established in the dog.
Dosages should usually be reduced in patients with renal failure, congestive heart failure or thosewho are critically ill.
Overdosage - Symptoms of overdosage can include hypotension, lethargy, confusion, nausea, vomiting, and oliguria. Cardiac signs may include widening of the QRS complex, junctionaltachycardia, ventricular fibrillation, or intraventricular conduction delays.
If an oral ingestion, emptying of the gut and charcoal administration may be beneficial to removeany unabsorbed drug. IV fluids, plus dopamine, phenylephrine, or norepinephrine could beconsidered to treat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may beused in an attempt to reduce the cardiotoxic effects of procainamide. Forced diuresis using fluidsand diuretics along with reduction of urinary pH, can enhance the renal excretion of the drug.
Temporary cardiac pacing may be necessary should severe AV block occur.
Procainamide may antagonize the effects of pyridostigmine, neostigmine, or other anticholinesterases in patients with myasthenia gravis.
Procainamide may potentiate the effects of other drugs having hypotensive effects.
Procainamide should only be used in patients with digitalis intoxication when treatment withpotassium, lidocaine or phenytoin is ineffective. Cimetidine may decrease the renal clearance ofprocainamide with a resultant increase in serum level of procainamide.
Procainamide may potentiate or prolong the neuromuscular blocking activity of muscle relaxantssuch as succinylcholine or other agents (e.g., aminoglycosides) having neuromuscular blockingactivity.
Procainamide HCl differs from procaine by the substitution of an amide group for the ester groupfound on procaine. It occurs as an odorless, white to tan, hygroscopic, crystalline powder with apKa of 9.23 and a melting range from 165°-169°C. It is very soluble in water and soluble in alcohol. The pH of the injectable product ranges from 4 - 6.
Storage, Stability, Compatibility
Oxidation due to the injection of air into the vial may causediscoloration of the injectable solution. The solution may be used if the color is no darker than alight amber. Refrigeration may retard the development of oxidation, but the solution may be storedat room temperature.The injectable product is reportedly compatible with sodium chloride 0.9% injection, and waterfor injection. Procainamide is also compatible with dobutamine HCl, lidocaine HCl, and verapamil
HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluentsused. It is suggested to consult specialized references for more specific information (e.g.,
Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology - PROCAINAMIDE HCL
A class 1A antiarrhythmic agent, procainamide exhibits cardiac actions similar tothat of quinidine. Procainamide prolongs the refractory times in both the atria and ventricles, decreases myocardial excitability, and depresses automaticity and conduction velocity. It has anticholinergic properties which may contribute to its effects. Procainamide's effects on heart rate areunpredictable, but it usually causes only slight increases or no change in heart rate. It may exhibitnegative inotropic actions on the heart, although cardiac outputs are generally not affected.On ECG, QRS widening, and prolonged PR & QT intervals can be seen. The QRS complex and T wave may occasionally show some slight decreases in voltage.
Uses, Indications - Procainamide is indicated for the treatment of ventricular premature complexes(VPC's), ventricular tachycardia, or supraventricular tachycardia associated with Wolff-Parkinson-White (WPW) syndrome with wide QRS complexes. Higher doses may be beneficial in thetreatment of supraventricular tachycardias, although procainamide cannot be considered a first-lineagent for this dysrhythmia.
Pharmacokinetics - PROCAINAMIDE HCL
After IM or IV administration, the onset of action is practically immediate.After oral administration in humans, approximately 75-95% of a dose is absorbed in the intestine, but some patients absorb less than 50% of a dose. Food, delayed gastric emptying or decreasedstomach pH may delay oral absorption. In dogs, it has been reported that the oral bioavailability isapproximately 85% and the absorption half-life is 0.5 hours. However, there is an apparent largedegree of variability in both bioavailability and half-life of absorption.
Distribution of procainamide is highest into the CSF, liver, spleen, kidneys, lungs, heart andmuscles. The volume of distribution in dogs is approximately 1.4 - 3 L/kg. It is only approximately20% protein bound in humans and 15% in dogs. Procainamide can cross the placenta and isexcreted into milk.
The elimination half-life in dogs has been reported to be variable, most studies report valuesbetween 2-3 hours. In humans, procainamide is metabolized to N-acetyl-procainamide (NAPA), anactive metabolite. It appears, however, that dogs do not form appreciable amounts of NAPA fromprocainamide. In the dog, approximately 90% (50-70% unchanged) of an intravenous dose isexcreted in the urine as procainamide and metabolites within 24 hours after dosing.
Contraindications/Precautions - Procainamide may be contraindicated in patients with myasthenia gravis (see Drug Interactions). Procainamide is contraindicated in patients hypersensitive toit, procaine or other chemically related drugs. In humans, procainamide is contraindicated in patientswith systemic lupus erythematosis (SLE), but it is unknown if it adversely affects dogs with thiscondition. Procainamide should not be used in patients with torsade de pointes, or with 2nd or 3rddegree heart block (unless artificially paced).
Procainamide should be used with extreme caution, if at all, in patients with cardiac glycosideintoxication. It should be used with caution in patients with significant hepatic or renal disease orwith congestive heart failure.
Adverse Effects, Warnings
Adverse effects are generally dosage (blood level) related in the dog.Gastrointestinal effects may include anorexia, vomiting, or diarrhea. Effects related to thecardiovascular system can include weakness, hypotension, negative inotropism, widened QRScomplex and QT intervals, AV block, multiform ventricular tachycardias. Fevers and leukopeniasare a possibility. Profound hypotension can occur if injected too rapidly IV. In humans, an SLEsyndrome can occur, but its incidence has not been established in the dog.
Dosages should usually be reduced in patients with renal failure, congestive heart failure or thosewho are critically ill.
Overdosage - Symptoms of overdosage can include hypotension, lethargy, confusion, nausea, vomiting, and oliguria. Cardiac signs may include widening of the QRS complex, junctionaltachycardia, ventricular fibrillation, or intraventricular conduction delays.
If an oral ingestion, emptying of the gut and charcoal administration may be beneficial to removeany unabsorbed drug. IV fluids, plus dopamine, phenylephrine, or norepinephrine could beconsidered to treat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may beused in an attempt to reduce the cardiotoxic effects of procainamide. Forced diuresis using fluidsand diuretics along with reduction of urinary pH, can enhance the renal excretion of the drug.
Temporary cardiac pacing may be necessary should severe AV block occur.
Drug Interactions
Use with caution with other antidysrhythmic agents, as additive cardiotoxic or other toxic effects may result.Procainamide may antagonize the effects of pyridostigmine, neostigmine, or other anticholinesterases in patients with myasthenia gravis.
Procainamide may potentiate the effects of other drugs having hypotensive effects.
Procainamide should only be used in patients with digitalis intoxication when treatment withpotassium, lidocaine or phenytoin is ineffective. Cimetidine may decrease the renal clearance ofprocainamide with a resultant increase in serum level of procainamide.
Procainamide may potentiate or prolong the neuromuscular blocking activity of muscle relaxantssuch as succinylcholine or other agents (e.g., aminoglycosides) having neuromuscular blockingactivity.