Editing Procainamide (section)

===Toxicity===
There is a close line between the plasma concentrations of the therapeutic and toxic effect, therefore a high risk for toxicity.<ref name="adverse" /> Many symptoms resemble [[systemic lupus erythematosus]] because procainamide reactivates [[hydroxylamine]] and [[nitroso]] metabolites, which bind to [[histone|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.<ref>{{cite journal | vauthors = Uetrecht J, Zahid N, Rubin R | title = Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes | journal = Chemical Research in Toxicology | volume = 1 | issue = 1 | pages = 74–78 | date = January 1988 | pmid = 2979715 | doi = 10.1021/tx00001a013 }}</ref> 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.<ref>{{cite journal | vauthors = Roberts SM, Adams LE, Donovan-Brand R, Budinsky R, Skoulis NP, Zimmer H, Hess EV | title = Procainamide hydroxylamine lymphocyte toxicity--I. Evidence for participation by hemoglobin | journal = International Journal of Immunopharmacology | volume = 11 | issue = 4 | pages = 419–427 | date = 1989 | pmid = 2476407 | doi = 10.1016/0192-0561(89)90089-1 }}</ref>

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.<ref>{{cite journal | vauthors = Gay RJ, Brown DF | title = Pacemaker failure due to procainamide toxicity | journal = The American Journal of Cardiology | volume = 34 | issue = 6 | pages = 728–732 | date = November 1974 | pmid = 4422040 | doi = 10.1016/0002-9149(74)90164-7 }}</ref> Thus, it prolongs QT interval of action potential and increases the risk of [[torsade de pointes]].<ref name=Osadchii/>

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.<ref name=Gould/>