Procainamide Hydrochloride

Procainamide is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In addition to blocking the INa current, it inhibits the IKr rectifier K+ current. Procainamide is also known to induce a voltage-dependent open channel block on the batrachotoxin (BTX)-activated sodium channels in cardiomyocytes. Procainamide is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In addition to blocking the INa current, it inhibits the IKr rectifier K+ current. Procainamide is also known to induce a voltage-dependent open channel block on the batrachotoxin (BTX)-activated sodium channels in cardiomyocytes. Procainamide is used for treating ventricular arrhythmias: ventricular ectopy and tachycardia and supraventricular arrhythmias: atrial fibrillation, and re-entrant and automatic supraventricular tachycardia. For example, it can be used to convert new-onset atrial fibrillation, though it is suboptimal for this purpose. It is administered by mouth, by intramuscular injection, or intravenously. It has been also been used as a chromatography resin because it somewhat binds protein. There are many side effects following the induction of procainamide. These adverse effects are ventricular dysrhythmia, bradycardia, hypotension and shock. The adverse effects occur even more often if the daily doses are increased. Procainamide may also lead to drug fever and other allergic responses. There is also a chance that systemic lupus erythematosus occurs, which at the same time leads to polyarthralgia, myalgia and pleurisy. Most of these side effects may occur due to the acetylation of procainamide. There is a close line between the plasma concentrations of the therapeutic and toxic effect, therefore a high risk for toxicity. Many symptoms resemble systemic lupus erythematosus because procainamide reactivates hydroxylamine and nitroso metabolites, which bind to histone proteins and are toxic to lymphocytes. The hydroxylamine and nitroso metabolites are also toxic to bone marrow cells and can cause agranulocytosis. These metabolites are formed due to the activation of polymorphonuclear leukocytes. These leukocytes release myeloperoxidase and hydrogen peroxide, which oxidize the primary aromatic amine of procainamide to form procainamide hydroxylamine. The release of hydrogen peroxide is also called a respiratory burst, which occurs for procainamide in monocytes but not in lymphocytes. Furthermore, the metabolites can be formed by activated neutrophils. These metabolites could then bind to their cell membranes and cause a release of autoantibodies which would react with the neutrophils. Procainamide hydroxylamine has more cytotoxicity by hindering the response of lymphocytes to T-cell and B-cell mitogens. Hydroxylamine can also generate methemoglobin, a protein that could hinder further oxygen exchange. It was also detected that the antiarrhythmic drug procainamide interferes with pacemakers. A toxic level of procainamide leads to decrease in ventricular conduction velocity and increase of the ventricular refractory period. This results in a disturbance in the artificial membrane potential and leads to a supraventricular tachycardia which induces failure of the pacemaker and death. Thus, it prolongs QT interval of action potential and increases the risk of torsade de pointes. Procainamide could initiate leukopenia and/or agranulocytosis, which are serious hematologic disorders, and is also known for causing gastrointestinal disturbances and aggravating pre-existing abnormalities in impulse initiation and propagation. Procainamide works as an anti-arrhythmic agent and is used to treat cardiac arrhythmia. It induces rapid block of the batrachotoxin (BTX)-activated sodium channels of the heart muscle and acts as antagonist to long-gating closures. The block is voltage-dependent and can occur from both sides; either from the intracellular or the extracellular side. Blocking from the extracellular side is weaker than from the intracellular side because it occurs via the hydrophobic pathway. Procainamide is present in charged form and probably requires a direct hydrophobic access to the binding site for blocking of the channel. Furthermore, blocking of the channel shows a decreased voltage sensitivity, which may result from the loss of voltage dependence of the blocking rate. Due to its charged and hydrophilic form, procainamide has its effect from the internal side, where it causes blockage of voltage-dependent, open channels. With increasing concentration of procainamide, the frequency of long blockage becomes less without the duration of blockage being affected. The rate of fast blocking is determined by the membrane depolarization. Membrane depolarization leads to increased blocking and decreased unblocking of the channels. Procainamide slows the conduction velocity and increases the refractory period, such that the maximal rate of depolarization is reduced.