Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.
Aim: The purpose of the study was to evaluate the sensitivity of patients to galvanic current after systemic cryotherapy. Material and Methods: Study group: 77 physiotherapists – hospital employees, aged 21-64 (AVG 29.4±9.5). The sensitivity was evaluated four times: before and immediately after the systemic cryotherapy procedure (1 session, 2 minutes, temperature -120°C), after exercising on a vertical cycle ergometer (20 minutes) and 4 hours after the procedure. The intensity of the galvanic current, which caused a slight tingling, was recorded. Two electrode placements were used: longitudinal on the upper limbs and transverse over the knee joints. Results: Statistical analysis revealed that the mean sensitivity to the galvanic current measured on both upper limbs or over the knee joints increases statistically significantly after systemic cryotherapy treatments. This effect persists even after 4 hours (Friedman’s ANOVA, p<0.001). Statistically significant increases in sensitivity to galvanic current were found compared to initial values for each pair of measurements, irrespective of electrode placement and test position (Wilcoxon test, p<0.01). The increase in sensitivity according to the measuring position concerned 68.8; 63.6; 72.7% of the participants on the left upper limb, on the right 61.0; 68.8; 74.0%, over the left knee joint 61.0; 68.8; 72.7% and over the right 58.4, 75.3 and 80.5% of the subjects in the study group. Conclusions: 1. After the administered systemic cryotherapy, sensitivity to galvanic current increases in most patients. 2. The increase in sensitivity to galvanic current depends on the time difference between treatments and is individually variable.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.