RESUMEN
Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington's disease, Parkinson's disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: ß-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient's pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine).
RESUMEN
Metabolic syndrome (MetS) is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Antipsychotic (AP)-induced MetS (AIMetS) is the most common adverse drug reaction (ADR) of psychiatric pharmacotherapy. Herein, we review the results of studies of blood (serum and plasma) and urinary biomarkers as predictors of AIMetS in patients with schizophrenia (Sch). We reviewed 1440 studies examining 38 blood and 19 urinary metabolic biomarkers, including urinary indicators involved in the development of AIMetS. Among the results, only positive associations were revealed. However, at present, it should be recognized that there is no consensus on the role of any particular urinary biomarker of AIMetS. Evaluation of urinary biomarkers of the development of MetS and AIMetS, as one of the most common concomitant pathological conditions in the treatment of patients with psychiatric disorders, may provide a key to the development of strategies for personalized prevention and treatment of the condition, which is considered a complication of AP therapy for Sch in clinical practice.
RESUMEN
The COVID-19 pandemic is a global public health challenge with understudied effects on antimicrobial usage. We aimed to analyze antimicrobial prescribing patterns in COVID-19 patients in Russian multi-field hospitals by means of the Global-PPS Project developed by the University of Antwerp. Out of 999 patients in COVID-19 wards in six hospitals surveyed in 2021, 51.3% received antimicrobials (79% in intensive care, 47.5% in medical wards). Systemic antivirals and antibiotics were prescribed to 31% and 35.1% of patients, respectively, and a combination of both to 14.1% of patients. The top antivirals administered were favipiravir (65%), remdesivir (19.2%), and umifenovir (15.8%); the top antibiotics were ceftriaxone (29.7%), levofloxacin (18%), and cefoperazone/sulbactam (10.4%). The vast majority of antibiotics was prescribed for treatment of pneumonia or COVID-19 infection (59.3% and 25.1%, respectively). Treatment was based on biomarker data in 42.7% of patients but was targeted only in 29.6% (6.7% for antibiotics). The rate of non-compliance with guidelines reached 16.6%. Antimicrobial prescribing patterns varied considerably in COVID-19 wards in Russian hospitals with groundlessly high rates of systemic antibiotics. Antimicrobial usage surveillance and stewardship should be applied to inpatient care during the COVID-19 pandemic.
RESUMEN
(1) Introduction: Extrapyramidal disorders form the so-called extrapyramidal syndrome (EPS), which is characterized by the occurrence of motor disorders as a result of damage to the basal ganglia and the subcortical-thalamic connections. Often, this syndrome develops while taking medications, in particular antipsychotics (APs). (2) Purpose: To review studies of candidate genes encoding dopamine receptors as genetic predictors of development of AP-induced parkinsonism (AIP) and AP-induced tardive dyskinesia (AITD) in patients with schizophrenia. (3) Materials and Methods: A search was carried out for publications of PubMed, Web of Science, Springer, and e-Library databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications were possibly missed. (4) Results: The review considers candidate genes encoding dopamine receptors involved in pharmacodynamics, including genes DRD1, DRD2, DRD3, and DRD4. We analyzed 18 genome-wide studies examining 37 genetic variations, including single nucleotide variants (SNVs)/polymorphisms of four candidate genes involved in the development of AIP and AITD in patients with schizophrenia. Among such a set of obtained results, only 14 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3 with AIP and rs4532 (A/G) DRD1, rs6277 (C/T), rs6275 (C/T), rs1800497 (C/T), rs1079597 (A/G), rs1799732 (141CIns/Del), rs1045280 (C/G) DRD2, rs6280 (C/T), rs905568 (C/G) DRD3 with AITD. However, at present, it should be recognized that there is no final or unique decision on the leading role of any particular SNVs/polymorphisms in the development of AIP and AITD. (5) Conclusion: Disclosure of genetic predictors of the development of AIP and AITD, as the most common neurological adverse drug reactions (ADRs) in the treatment of patients with psychiatric disorders, may provide a key to the development of a strategy for personalized prevention and treatment of the considered complication of AP therapy for schizophrenia in real clinical practice.
RESUMEN
Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.
RESUMEN
Antimicrobial resistance is one of the key issues limiting the successful treatment of infectious diseases and associated with adverse medical, social and economic consequences on a global scale. The present study aims to evaluate antimicrobials prescribing patterns and assess progress in quality indicators in Russian multidisciplinary hospitals using three repetitive point prevalence studies (PPSs) over 4 years (Global-PPS 2015, 2017 and 2018). Out of 13,595 patients from 21 hospitals surveyed over the three time points, 3542 (26.14%) received antimicrobials, predominantly third-generation cephalosporins (44.7% in 2015, 34.1% in 2017 and 41.8% in 2018). Compliance with the hospital antibiotic guidelines was 74.8%, 66.8% and 74.3%, respectively. Indication for treatment was recorded in 72.6%, 84.1% and 82.6%, while stop/review date was documented only in 40.5%, 46.5% and 61.1% of cases. Perioperative antibiotic prophylaxis exceeded 1 day in 92%, 84% and 81% of cases. Targeted therapy rate at all time points did not exceed 15.1%, treatment based on the biomarkers rate-19.9%. For the part of PPS-2017 and 2018 analyzed in dynamics, no prominent trends were noted. The results of the project provide the basis for the development of appropriate antimicrobial stewardship programs tailored according to local practices for each hospital in the project.
