Pharmacotherapy in a Multidisciplinary Paediatric Hospital: Polypharmacy and Drug–Drug Interaction Risk Illustrated with a Clinical Case

Nowadays, the problems caused by polypharmacy are recognised and widely discussed in the medical community. Multimorbidity, which is not uncommon in paediatric practice, comes with an increase in the number of prescriptions and necessitates an active search for tools to reduce the potential risk and frequency of adverse drug–drug interactions in paediatric patients.The aim of the study was to use a clinical case to illustrate the need for monitoring, including laboratory monitoring of pharmacokinetic parameters, during concomitant therapy in paediatric practice.Materials and methods: the study consisted in a retrospective analysis of the archived medical records of an 11-year-old child with nephrotic syndrome associated with a concomitant tuberculous process who had been receiving inpatient treatment with immunosuppressants at the Russian Children’s Clinical Hospital from May to July 2018.Results: the prescription of cyclosporine for nephrotic syndrome entailed monitoring of plasma drug levels for potential pharmacokinetic interactions with the medicinal products used to treat the concomitant disease. The monitoring revealed an interaction between cyclosporine and rifampicin at the level of biotransformation. An adjustment of the concomitant therapy (discontinuation of rifampicin) allowed for achieving the target blood cyclosporine concentration, decreasing proteinuria and hypercholesterolemia, and increasing the blood total protein level in the child, which indicated the effectiveness of the ongoing treatment for the chief complaint.Conclusions: the data obtained suggest that laboratory monitoring of pharmacokinetic parameters in paediatric polypharmacy can increase the effectiveness of therapy and prevent adverse reactions and irrational combination of medicinal products

Оценка безопасности лекарственной терапии в клинической практике Костылева М.Н.1,2, Белоусов Ю.Б.2, Грацианская А.Н.1,2,

the present review is devoted to an actual problem of safety of pharmacotherapy in clinical practice; the particular attention is paid to the state of this problem in pediatrics. Information about pharmacovigilance is proposed; criteria of definition, methods of collecting (their advantages and limitations), account and analysis of the adverse reactions of drugs in post-marketing period are described. The off label use of drugs in children and a role of clinical pharmacologist in the adverse reactions of drugs monitoring in a hospital is discussed.настоящий обзор посвящен актуальной проблеме безопасности фармакотерапии в клинической практике, отдельное внимание уделено состоянию проблемы в педиатрии. Предлагаются сведения о фармаконадзоре: описаны критерии определения, методы сбора (их преимущества и недостатки), учета и анализа нежелательных явлений лекарств на пострегистрационном этапе. Обсуждается проблема off label назначений лекарств у детей и роль врача-клинического фармаколога в организации мониторинга нежелательных явлений в условиях стационара

EVALUATION OF SAFETY OF DRUG THERAPY IN CLINICAL PRACTICE

the present review is devoted to an actual problem of safety of pharmacotherapy in clinical practice; the particular attention is paid to the state of this problem in pediatrics. Information about pharmacovigilance is proposed; criteria of definition, methods of collecting (their advantages and limitations), account and analysis of the adverse reactions of drugs in post-marketing period are described. The off label use of drugs in children and a role of clinical pharmacologist in the adverse reactions of drugs monitoring in a hospital is discussed

Drug induced haematotoxicity

The main types of hematological complications related to ongoing pharmacotherapy - (different types of cytopenia, as well as coagulopathy) are presented. The risk factors and mechanisms of development of these disorders are discussed. The authors emphasize the importance of awareness by doctors of the existence of drug induced pathology (disease) as a separate type of iatrogeny

REYE-LIKE SYNDROME IN THREE-YEAR-OLD CHILD

The article reviews the literature on classical and atypical Reye’s syndrome, explores the circumstances that contribute to its  occurrence, provides criteria for diagnosing with an illustration in the form of an authentic case of Reye-like disease in a child of 3 years  old. Reye’s syndrome is a disease manifested by acute  encephalopathy in combination with fatty degeneration of the  internal organs, mainly the liver. This condition was first described in  1963 by an Australian pathologist who identified 21 cases of the  disease in children with influenza A who were taking acetylsalicylic  acid, 17 children died. In the future, the circle of infections that  preceded the development of Reye’s syndrome-acute respiratory  infections, chickenpox, entero- and rotavirus infections, in rare  cases, hepatitis A and HIV, bacterial infections: mycoplasma,  chlamydia, whooping cough, shigella, salmonella. Drugs that can cause the development of this syndrome: tetracycline,  zidovudine, diclofenac sodium, mefenamic acid, paracetamol,  amiodarone, warfarin, phenothiazine derivatives, histaminolytics  (dimedrol), valproic acid. Along with drugs, insecticides, herbicides,  hepatotoxic fungi can be used as triggers of the syndrome. There is  an age dependence of the development of this syndrome. The  pathogenesis of classic Reye’s syndrome is associated with  generalized damage to the mitochondria primarily in the brain, as well as in the liver, kidneys, muscles, myocardium and pancreas,  with the disturbance of oxidation of fatty acids in them and the  formation of fat degeneration of varying degrees. In addition to the  classic Reye’s syndrome, atypical Reye’s syndrome or Reye-like  disease is isolated, occurs in children under 5 with congenital  disturbance of oxidation of fatty acids. We observed in our clinic the  case of Reye-like disease in a girl of three years with infection and  taking antipyretics. In the discussion section, the features of the  given case are noted, the question of the appropriateness (in view of the generality of the clinic and the mechanisms of development) of  dividing the syndrome into classical and atypical is discussed. A new  name for both conditions is proposed — Reye’s disease in honor of  the discoverer, highlighting its two forms with an early and late  onset. Given the morphological changes in this syndrome —  steatosis of internal organs — authors seem to be appropriate  measures aimed at treating secondary mitochondrial insufficiency  and fatty dystrophy

The Case of Сushing Syndrome in a Child of 15 Years after Prolonged Endonasal Use of Dexamethasone

Abstract. The article describes the case of drug Cushing syndrome as a result of prolonged (for 10 months) endonasal use of dexamethasone and oxymetazoline mixture, which was prepared by the patient’s mother. Medical control was absent. The content of dexamethasone in the vial and the concentration of oxymetazoline was not known. During the examination, in addition to Cushing syndrome, an atrophy of the nasal mucosa as a second side effect was revealed. Thus, in the above case, there were two complications of incorrect using of drugs — local and systemic

Clinical and Instrumental Characteristics of Newly Diagnosed Patients with Various Forms of Pulmonary Hypertension according to the Russian National Registry

Aim. To study demographic and clinical characteristics and to give a comparative description of the functional and hemodynamic status, profile of concomitant pathology in patients with various forms of pulmonary arterial hypertension (PAH), and chronic thromboembolic pulmonary hypertension (CTEPH) according to the Russian National Registry. Methods. During the period from January 01, 2012, till January 01, 2019, 1105 patients aged >18 years with verified diagnosis of PAH and CTEPH, who were subsequently observed at 15 PH expert centers of the Russian Federation in the 52 provinces, are included in the Russian registry on the basis of the Federal State Budgetary Institution of Cardiology of the Ministry of Healthcare of Russia. All newly diagnosed patients (n=727) were entered into the registry database (NCT03707561). A comparative analysis of demographic and clinical characteristics, profile of concomitant pathology, and parameters of a comprehensive examination of patients was performed. Results. Among newly diagnosed patients, 67% had PAH and 28.3% had CTEPH. In the PAH group, 40.9% of patients had idiopathic arterial PAH (IPAH), 36.6% had PAH associated with simple congenital heart disease (PAH-CHD), 19.3% had PAH associated with systemic connective tissue disease (PAH-CTD), 1.8% had portal pulmonary hypertension (PoPH), 0.6% had PAH associated with HIV infection (PAH-HIV), 0.4% had heritable PAH (HPAH), and 0.4% had drug/toxin-induced PAH. At the time of diagnosis, PAH patients were younger than patients with CTEPH (45.2±14.9; 52.6±15.3 years, respectively) (p<0.05). At the time of diagnosis, 71% PAH and 77% CTEPH patients had WHO FC III/IV. Mean (±SD) 6MWD was significantly less in CTEPH vs. the PAH group 331.3±110.3 vs. 361.8±135.7 m (p=0.0006). Echo data showed a comparable sPAP between groups; CTEPH population had a more pronounced increase in the area of the right atrium (SRA) (24 [20; 32] cm2 and 19 [15; 26] cm2, respectively), and a significant decrease in FAC (24.7 [22, 4; 29.0] and 29.0 [23.0; 31.0] %, respectively) as compared to the PAH group. RHC showed a comparable increase of sPAP and mPAP in PAH and CTEPH groups. 15.2% of patients with IPAH and HPAH demonstrated positive results in the acute vasoreactivity testing. CTEPH patients were more often obese and suffered from arterial hypertension and right heart failure. Deep venous thrombosis was significantly more often observed in patients with CTEPH (53%). The most common concomitant pathology was erosive-ulcerative lesion of the stomach/duodenum, less often of the esophagus (23.5% and 44.5%, respectively). Conclusion. According to the Russian registry in patients with PAH and IPAH, the diagnosis is established at a younger age in comparison with the European registries. CTEPH patients are characterized by more severe functional status, pronounced signs of right heart failure taking into account the older age and the spectrum of comorbid pathology, which limits the possibility of surgical treatment. An increase in the number of expert centers participating in the registry is the key to improving early diagnosis of PH and optimal follow-up according to common standards in order to timely optimize therapy and reduce mortality of patients