The paper presents data on the coronavirus diseaseCOVID-2019 caused by the SARS-CoV-2 coronavirus, which was temporarily named 2019-nCoV (2019 novel coronavirus) until 11 February 2020. An outbreak of pneumonia of unknown etiology in Wuhan (Hubei province of China) which was first described in an official publication of the Chinese Office of the World Health Organization on December 31, 2019, attracted attention of both dedicated experts and the entire international community. On January 30, 2019 it was recognised as a public health emergency of international concern. The first cases were reported on December 12, 2019 in China, and on January 31, 2020 Russia reported its first two cases of the infection in two Chinese citizens staying in Russia. The causative agent is the new SARS-CoV-2 coronavirus. It had not been detected before, and was first identified by Chinese researchers on January 7, 2020 under the temporary name 2019-nCoV. The aim of the study was to summarise information about coronavirus diseaseCOVID-2019 beginning from the onset of the epidemic until early March 2020. The paper provides general information about coronaviruses, developments of the COVID-2019 epidemic caused by the SARS-CoV-2 coronavirus, and gives an assessment of the global epidemiological situation. It cites the recommendations of national regulatory authorities and the World Health Organization on the treatment of various forms of coronavirus infection and septic shock caused by SARS-CoV-2, including target values of systemic hemodynamics, a list of recommended medicines, methods of their use, and limitations of pharmacotherapy.

The introduction into clinical practice of immune checkpoint inhibitors that block cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1), has improved the prognosis of patients with malignant neoplasms of diff erent localisation. The antitumour eff ect of immune checkpoint inhibitors is based on blocking CTLA-4 and PD-1/PD-L1 signaling pathways and enhancing lymphocyte antitumour activity. However, inhibition of immune checkpoints may lead to dysregulation of immune responses and appearance of a new type of adverse reactions resulting from changes in the activity of immunocompetent cells. The aim of the study was to analyse adverse reactions associated with the use of immune checkpoint inhibitors. It was demonstrated that the structure of immune-mediated adverse reactions varied depending on the class of immune checkpoint inhibitors. The incidence of immune-mediated adverse reactions was higher with CTLA-4 inhibitors as compared with PD-1/PD-L1 inhibitors, and increased signifi cantly in the case of combination therapy. The treatment with CTLA-4 inhibitors most often resulted in skin reactions (rash, itching), gastrointestinal tract reactions (diarrhea, colitis), and endocrine gland problems (hypophysitis). The treatment with PD-1 inhibitors most often led to respiratory disorders (pneumonitis), and in some cases to gastrointestinal disorders (diarrhea, colitis), skin reactions (rash, itching), and endocrine gland problems (hypothyroidism), but they were less common. The treatment with PD-L1 inhibitors was associated with the development of pneumonitis. The development of immune-mediated adverse reactions may require discontinuation of treatment and administration of immunosuppressants, therefore early diagnosis and timely treatment of complications are important prerequisites for successful antitumour therapy. Further study of the mechanisms of immune-mediated adverse reaction development will optimise antitumour therapy with immune checkpoint inhibitors. 

Despite all the achievements of modern medicine, heart failure remains one of the most prevalent, severe and prognostically unfavorable conditions that requires close attention of the medical community. The diversity of the clinical picture and the large number of co-morbidities go hand in hand with a rather complicated pharmacotherapy regimen which, in the vast majority of cases, includes several medicines. Some classes of drugs can provoke the onset/progression of heart failure in patients with left ventricular dysfunction, as well as contribute to the development of heart failure in patients without concomitant cardiovascular diseases. The aim of the study was to analyse and systematise data on risk factors for the development of drug-induced heart failure and data on its prevalence when using various groups of medicines. It has been established that drug-induced heart failure typically develops in association with the use of calcium channel blockers (verapamil, diltiazem, nifedipine), beta-blockers (propranolol), antiarrhythmic drugs (disopyramide, dronedarone, lidocaine, lorcainide, mexiletine, moricizine, propafenone, tocainide, flecainide, encainide), hypoglycemic drugs (rosiglitazone, pioglitazone, saxagliptin), anthracyclines (doxorubicin, epirubicin) and other anticancer drugs (bevacizumab, infliximab, trastuzumab), and non-steroidal anti-infl ammatory drugs (diclofenac, ibuprofen, celecoxib, rofecoxib). It is assumed that this pathology develops in a small number of patients, mainly those who already have left ventricular dysfunction. However, the effects of drugs should be considered as one of potential and preventable causes of heart failure development/progression. Raising clinicians’ awareness of the potential adverse effects of individual medicines or entire pharmacological classes of drugs on the cardiac function, especially in patients with left ventricle dysfunction, can facilitate the timely diagnosis and prevention of drug-induced heart failure. 

The implementation of a complex risk-oriented approach at all stages of drug development, including the preclinical research stage, is essential for ensuring drug safety, quality and effi cacy. The aim of the study was to justify the benefits of introducing risk management into the integrated quality management system at the preclinical trial stage. The optimal approach to implementing risk management system at the preclinical stage is an overall process approach based on the international standard ISO 31000:2009 Risk management—Principles and guidelines. This approach as applied to a preclinical research centre includes a three-tier risk management system at the level of operational process subsystems, the level of the testing centre’s departments, and the level of an individual preclinical study. The common components of the subsystems may include concepts, organisational structure, information exchange system, documentation structure, etc. The process of risk management as applied to the subsystems includes risk identification, analysis, assessment, and response to the risk. The response to the risk is an iterative process that includes selection of response options, response planning, and implementation of response activities from control procedures to corrective and preventive actions. The integration of the preclinical risk management system into the organisation’s overall management system, which includes the occupational health and safety management system and the quality management system, will enhance the capabilities of the individual systems to achieve a high quality level of research, preserve the staff ’s professional health, make informed management decisions within the organisation, increase preparedness for external audits, and gain competitive advantages.

Statins are efficacious lipid-lowering drugs used for prevention of cardiovascular complications in patients with high blood cholesterol. The efficacy and safety of this group of drugs is largely determined by genetic factors. The aim of the study was to analyse the effect of gene polymorphisms on the efficacy and safety of atorvastatin in patients undergoing hospital treatment. Materials and methods. The authors carried out a retrospective study of the medical records of 76 hospital patients who were prescribed atorvastatin for confirmed hyperlipidemia. All the patient records contained the results of genotyping of single nucleotide polymorphisms that presumably affect the pharmacokinetics and pharmacodynamics of statins. Results. The analysis of literature data suggested that the pharmacological response and safety of statins could be affected by polymorphisms of the following genes: SLCO1B1, ABCB1, CYP2C9, and CYP2C19. The study showed that atorvastatin had high efficacy in the carriers of the 3435C allele of the ABCB1 gene and in the carriers of the CYP2C19*2 allele of the CYP2C19 gene. The patients carrying ABCB1 genotypes demonstrated a tendency to increasing levels of low-density lipoproteins and total cholesterol in the following order: 3435СС → 3435СТ → 3435ТТ. The only adverse reaction of atorvastatin in the patient groups was an increase in the activity of hepatic transaminases, however, no connection with the studied gene polymorphisms was observed. Conclusions. The study of the effect of gene polymorphisms on the efficacy and safety of statins will be continued to obtain statistically valid confirmation of the observed trends in a much larger group of patients.

Analysis of administrative decisions of foreign regulatory authorities on the recoil of medicines and/or the need for changes in the instructions for their medical use due to changes in the safety profi le, conducted by experts of the Scientifi c Centre for Expert Evaluation of Medicinal Products revealed 16 administrative decisions. These decisions contained information on the following medicines registered in Russia: norepinephrine, xylometazoline, mometason, liraglutide recombinant, exenatide, insulin recombinant human, insulin degludec, teriparatide, progesterone, gestodene, desogestrel, dienogest, drospirenone, norgestrel, lynestrenol, levonorgestrel, medroxyprogesterone, mestranol, nomegestrol, norethisterone, norgestimate, chlormadinone, cyproterone, estradiol, ethinylestradiol, etonogestrel, ethinylestradiol, fi nasteride, abiraterone, thiamazole, omega-3-acid ethyl esters, pitavastatin.