Procainamide

It is a derivative of procaine which is a local anesthetic.

Mechanism of action:
Same as that of quinidine

Actions:
Cardiac effects:

Almost similar to quinidine.

It decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.

However unlike quinidine it has less effecient antimuscarinic action.

Due to its ganglionic receptor blocking properties, it results in more pronounced negative inotropic effects than quinidine.

It instigates serious CCF in patients with already ventricular dysfunction.

Other effects:
It reduces peripheral vascular resistance and may cause hypotension due to its ganglionic blocking properties.

Pharmacokinetics:

Procainamide is well-absorbed orally.

Its half life is 2 – 3 hours. Some of the procainamide is metabolized in the liver into N-acetylprocainamide (NAPA). NAPA has the same properties as that of class III agents as it prolongs the duration of action potential.

Therapeutic uses:

It is used in atrial and ventricular arrhythmias and ventricular arrhythmias which comes with acute myocardial infarction.

Adverse effects:
It may cause mental confusion, anorexia, nausea, urinary retention and hepatitis. After prolonged use, it may cause reversible form of lupus erythematosus like syndrome in 20-30 percent of patients. Its toxic dose may cause asystole or instigation of ventricular arrhythmias.

Its effects on CNS include depression, hallucination and psychosis.

Contraindications:
It is contraindicated in patients with AV block or systemic lupus erythematosus.

Dosage:
It is given up to 50 mg/kg daily in divided doses every 3 to 6 hours.

Pharmaceutical Management

The careful management and skillful administration of the business of pharmaceuticals is referred to as Pharmaceutical Management.

Quinidine

It is one of the alkaloids of cinchona also known as beta-quinine (it is an a C-9 epimer of quinine). Quinidine is also referred to as conquinine. It is the most primitive form of class IA drug.

Mechanism of action:
Its most important effect is on Phase 0 of the action potential causing a decrease in rapid depolarization by blocking the sodium channels.

It affects Phase 4 also when there is slow depolarization by slow opening of sodium channels.

Actions:
It causes the inhibition of ventricular arrhythmias, reentry arrhythmia and arrhythmias originating from other than normal place.

Cardiac effects:

High concentration of Quinidine directly affects the cardiac cells whereas low concentrations of Quinidine causes indirect (anti-cholinergic) effects on the heart.

Quinidine decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.

It increases duration of action potential which along with promoted effective refractory period decreases maximum reentry frequency.
Quinidine has α-adrenoceptor blocking properties which causes vasodilation and a reflex increase in SA nodal rate.

Other effects:
It has

1. antimalarial,
2. antipyretic and
3. oxytocic properties, so that increasing the contractions of the muscles of the womb during childbirth.

Pharmacokinetics:
Quinidine sulfate is well absorbed orally. It is metabolized in the liver by cytochrome p450 enzyme and excreted through the kidneys.

Therapeutic uses:
It is used for

1. Atrial, AV junctional and ventricular tachyarrhythmias
2. Premature atrial and ventricular contractions
3. It has the ability of maintaining sinus rhythm after sudden outburst of atrial fibrillations and flutter
4. Interatrial and atrioventricular nodal reentrant arrhythmias
5. Wolf Parkinson white tachycardia

Adverse effects:
Cinchonism (characterized by headache, tinnitus, photophobia, confusion), Anorexia, Gastrointestinal intolerance (Nausea), Rashes, Hepatitis

It may cause worsening of arrhythmia. It may block SA or AV nodes.

Classification of the anti-arrhythmic drugs

Detailed Classification of Anti-arrhythmic drugs

Class I (Na+ Channel blockers):

Class IA drugs (Fast Channel Blockers):
Quinidine, Procainamide, Disopyramide, Imipramine, Amiodarone, Moricizine, Diphenylhydantoin, Ajmaline, Dronedarone, KB130015

Class IB drugs:
Lidocaine, Tocainide, Mexiletine, Phenytoin

Class IC drugs:
Flecainide, Encainide, Indecainide, Lorcainide, Propafenone
Class II Drugs (β-blockers):
Propranolol, Esmolol, Atenolol, Timolol, Metoprolol, Bisoprolol

Class III Drugs (K-Channel blockers):
Amiodarone, Sotalol, Bretylium, Dofetilide, Ibutilide, N-acetylprocainamide, Almokalant, Nibentan, Nifekalant, Azimilide, AVE0118, Ronalozine

Class IV drugs (Ca-Channel blockers or Slow Channel Blockers):
(V) Verapamil, Diltiazem, Bepridil, Nifedipine

Class V drugs:
Digitalis, Adenosine, Digoxin

Miscellaneous Drugs:
Magnesium, Potassium, BIIB-513, Cariporide, H345/52, SSR149744C, Tecadenoson, Tedisamil, ZP123

Further Reading:
Current Trends in Pharmacology by Ray, A.and Gulati, K. 2007, International Publishing house private Ltd.

Fundamental Approaches to the management of Cardiac Arrhythmias by Sung, R. J. and Lauer, M. R. 2000, Kluwer Academic Publishers.

Physiology and Pharmacology of the Heart by Brown, H.; Kozlowski, R. and Davey, P. 1997, Willey Blackwell.