Disease relevance of Novocainamide

• No objective marker for symptomatic procainamide-induced lupus has been described [1].
• Twenty-six of these patients, who had ventricular fibrillation during single-drug therapy with quinidine, procainamide, or disopyramide, were compared with a control group of 62 patients who had been treated similarly for ventricular arrhythmias but did not have ventricular fibrillation during treatment [2].
• Transplacental cardioversion of fetal supraventricular tachycardia with procainamide [3].
• In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia [4].
• The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia [4].

Psychiatry related information on Novocainamide

• Such antibodies were infrequent in the long-term therapy group, most of whose members exhibited anti-single-strand DNA and were symptomatic with overt procainamide-induced lupus [5].
• Sixty-seven patients on treatment with procainamide were examined for the presence of two common idiotypes of anti-DNA antibodies (16/6 Id and 32/15 Id) [6].
• CASE SUMMARY: A 77-year-old woman with a history of hypertension, insulin-dependent diabetes mellitus, temporal arteritis, and Wolff-Parkinson-White syndrome who had taken procainamide for six weeks presented to the hospital with disorientation and acute renal and hepatic dysfunction [7].
• In these studies, we showed that NAPA has an elimination-phase half-life that is more than twice as long as procainamide and suggested that patient compliance and arrhythmia suppression might be improved if NAPA were used to circumvent the inconvenience of the frequent dosing schedule that has been recommended for procainamide [8].

High impact information on Novocainamide

• Association of antibody to histone complex H2A-H2B with symptomatic procainamide-induced lupus [1].
• Procainamide: autoimmune phenomena and acetylator phenotype [9].
• Positive direct antiglobulin tests and immune hemolytic anemia in patients receiving procainamide [4].
• Mice injected in the thymus with procainamide-hydroxylamine, a metabolite of procainamide, develop autoimmune features resembling drug-induced lupus [10].
• When cases of torsades de pointes were analyzed by individual drug, observed female prevalence was always greater than expected, representing a statistically significant difference (P < .05) for all agents except procainamide [11].

Chemical compound and disease context of Novocainamide

• Less convincing, but suggestive evidence exists for: 1-asparaginase, iatrogenic hypercalcemia, chlorthalidine, corticosteroids, ethacrynic acid, phenformin, and procainamide [12].
• Remission of procainamide-induced lupus erythematosus with N-acetylprocainamide therapy [13].
• An 82-year-old woman developed symptomatic reactive hypoglycemia in the same year she developed a lupus-like syndrome, probably secondary to the administration of procainamide or hydralazine [14].
• Agranulocytosis, procainamide, and phenytoin [15].
• The effect of lidocaine (n = 6) and procainamide (n = 12) on electrogram characteristics from electrically normal right ventricular and electrically abnormal left ventricular endocardial sites was determined in 18 patients with prior myocardial infarction [16].

Biological context of Novocainamide

• Circulating thrombin time anticoagulant in a procainamide-induced syndrome [17].
• Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease [18].
• The profound biologic activity of this metabolite and its possible generation within lymphoid compartments implicate this process in the induction of autoimmunity by procainamide [19].
• These studies demonstrate the capacity of neutrophils to mediate metabolism of procainamide and establish the role of myeloperoxidase released during degranulation and H2O2 derived from the respiratory burst in the direct cooxidation of procainamide to PAHA [19].
• Immediate-release and sustained-release procainamide: bioavailability at steady state in cardiac patients [20].

Anatomical context of Novocainamide

• Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro [21].
• This study examines the capacity of neutrophils to metabolize procainamide to reactive forms [19].
• Murine CD4+ T cells were treated with 5-azacytidine or procainamide and were shown to respond to syngeneic antigen-presenting cells, similar to CD4+ human T cell clones treated with these drugs [22].
• Lymphocyte alteration by procainamide: relation to drug-induced lupus erythematosus syndrome [23].
• These data show that 1) the delivery of high transmural concentrations of PA directly into infarcted myocardium is both feasible and effective.. [24].

Associations of Novocainamide with other chemical compounds

• Metabolism of procainamide to the cytotoxic hydroxylamine by neutrophils activated in vitro [19].
• Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice [22].
• Demethylation induced by 5-aza-2'-deoxycytidine and procainamide enhanced the transcription and activity of the 11 beta HSD2 enzyme in human cells in vitro and in rats in vivo [25].
• Electrophysiologic comparative study of procainamide and N-acetylprocainamide in anesthetized dogs: concentration-response relationships [26].
• The difference in the group mean lipid values for patients receiving and not receiving type Ia antiarrhythmic agents (quinidine, procainamide, and disopyramide) was evaluated by the two-sample t test, and multiple linear regression analyses were performed to adjust for relevant covariates [27].

Gene context of Novocainamide

• We report here that the drug procainamide, a nonnucleoside inhibitor of DNA methyltransferases, reversed GSTP1 CpG island hypermethylation and restored GSTP1 expression in LNCaP human PCA cells propagated in vitro or in vivo as xenograft tumors in athymic nude mice [28].
• Recombinant NAT2 and the liver NAT2 isoforms NAT2A and NAT2B selectivity N-acetylated the "polymorphic" substrates sulfamethazine and procainamide, whose disposition in vivo is affected by the acetylation polymorphism [29].
• Role of CYP2D6 in the N-hydroxylation of procainamide [30].
• OCTN1-mediated [14C]TEA uptake was inhibited by various organic cations such as cimetidine, procainamide, pyrilamine, quinidine, quinine, and verapamil [31].
• Characterisation of recombinant HERG K+ channel blockade by the Class Ia antiarrhythmic drug procainamide [32].

Analytical, diagnostic and therapeutic context of Novocainamide

• There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05) [4].
• Retrospective studies of patients in whom procainamide lupus had developed revealed that the duration of therapy required for induction in 14 slow and seven rapid acetylators was 12 +/- 5 and 48 +/- 22 months respectively (P less than 0.002) [33].
• Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide [18].
• Neutrophils activated with opsonized zymosan were cytotoxic only if procainamide was present, whereas N-acetyl procainamide, which does not induce autoimmunity, was inert in this bioassay [19].
• A case-control study showed a significant association between sustained-release procainamide therapy and severe neutropenia in 5 of 114 patients (4.4%) recovering from open-heart surgery (Mantel-Haenszel chi square = 13.84; p less than 0.001) [34].

References