scholarly journals Food-drug interaction as a risk factor of drug-induced diseases: epidemiology, risk factors, potential mechanisms of interaction

2021 ◽  
pp. 31-38
Author(s):  
A. P. Pereverzev ◽  
O. D. Ostroumova
Keyword(s):  
Kinase Inhibitor ◽  
Clinical Manifestations ◽  
Pharmacokinetic Profile ◽  
Empty Stomach ◽  
Quantitative Composition ◽  
Drug Induced ◽  
Qualitative And Quantitative ◽  
Effect Of Food ◽  
Potential Interactions ◽  
High Calorie

Any drug is potentially associated with the risk of adverse drug reactions (ADRs), the incidence of which in developed and developing countries is estimated at 6.3 (3.3—11.0) and 5.5 % (1.1—16.9), respectively. Many ADRs increase mortality and / or morbidity and / or cause clinical manifestations that require a patient to seek medical help or hospitalization; a special term has been introduced — drug-induced diseases. Food can interact with drugs and increase the risk of ADRs, including serious ones. The simultaneous intake of food and drugs can affect the bioavailability, pharmacokinetics, pharmacodynamics and therapeutic efficacy of drugs due to changes in drug absorption and metabolism. A striking example of the effect of food on the pharmacokinetic profile of drugs is the change in the bioavailability of the tyrosine kinase inhibitor lapatinib: compared with taking on an empty stomach, the bioavailability of lapatinib in a single dose of 1 500 mg after taking it together with high-calorie standard food increases by an average of 325 % — 4.25 times. In other words, the concentration of the drug in the blood serum after taking one tablet at the same time with food is comparable to taking 4 tablets on an empty stomach. Currently, there are no recommendations for choosing a dosage regimen for drugs depending on the qualitative and quantitative composition of food, as well as taking into account potential interactions with food components, although these recommendations are extremely necessary for patients and healthcare professionals. In this regard, this article summarizes the data available at the time of writing in open sources concerning the effect of food on the absorption and metabolism of drugs, and also describes the possible mechanisms of interaction.

scholarly journals POS0083 USEFUL EXPERIENCE OF RHEUMATOLOGISTS FOR UNDERSTANDING OF THE DISEASE ORIGIN AND APPROACHES TO THERAPY IN FIBRODYSPLASIA OSSIFICANS PROGRESSIVA

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 249.2-250
Author(s):  
I. Nikishina ◽  
S. Arsenyeva ◽  
V. Matkava ◽  
A. Arefieva ◽  
M. Kaleda ◽  
...  
Keyword(s):  
Heterotopic Ossification ◽  
Kinase Inhibitor ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Rapid Progression ◽  
Time Duration ◽  
Long Term Follow Up ◽  
Vertebral Bodies ◽  
The One

Background:Many monogenic genetic conditions, such as auto-inflammatory diseases (AIDs), have similar clinical manifestations and immunopathogenesis to “classic” rheumatic diseases (RD). Such cases may include Fibrodysplasia ossificans progressiva (FOP), an extremely rare genetic disease, which, according to our previous study and data from other authors1, may represent an example of AID with catastrophic heterotopic ossification due to a mutation in the ACVR1 gene. it seems that the experience of rheumatologists, especially children’s ones, will be useful in the treatment of FOP.Objectives:To analyzed the dynamics of clinical manifestations and to therapy approaches including target anti-inflammatory drug Tofacitinib (TOFA) in the one of the world’s largest groups of patients (pts) with FOP.Methods:The study was based on the analysis retrospective and prospective observation of the 35 pts (17 males and 18 females) with a verified diagnosis of FOP for the period from 1998 to 2020. In 9 pts with severe course of FOP TOFA administration were evaluated.Results:In all 35 pts the diagnosis was verified by “classic” FOP phenotype: malformed great toes in 33 pts (94,3%); short malformed thumbs-8 (22.8%); peripheral osteochondromas-20 (57.1%); abnormalities of the cervical spine-32 (91.4%), multiple heterotopic ossifications-32 (91,4%). Genetic tests were done in 26, it confirmed mutation in the ACVR1 gene in 100%. Long term follow-up detected a lot of spondyloarthritis-like signs similar to the manifestation of RD: ankylosis of the facet joints and vertebral bodies (by the type of syndesmophytes) in most pts, sacroiliitis, confirmed by radiological methods (X-ray, CT, MRI), gradual ankylosis in the peripheral joints in 18 (56.4%), synovitis in large joints in 8 (25%) pts (knee and hip mostly). In 9 pts with the most difficult course with rapid progression of ossification due to continuous flares despite the NSAIDs and steroids intake, we tried to use TOFA after the approval of the local Ethic Committee. We use the similar dose to randomized trial for JIA (up to 5 mg twice a day). The first patient was 16 y.o. at the time of TOFA administration in December 2019, the age of the other pts was from 2 to 12 y.o. By present time duration of TOFA therapy is from 6 to 15 mo. For the previous 6 months before TOFA initiation the number of flares was in average 8 per patient. After 6 months of TOFA treatment the number of new flares decreased to 0-1, except youngest patient of 2 y.o. in whom the number of flares decreased from 10 to 4 per the same period. In all 9 pts we minimize the dose or completely stop the steroids. New nodes formation stopped immediately in most pts and also the significant motion improvement of large (shoulder) joints were established. Drug tolerance was good in all pts, no AE were registered. But despite the good clinical effect without new heterotopic ossification in our first patient, we found continuous intraskeletal ossification between vertebral bodies, facet and sacroiliac joints in MRI.Conclusion:We are confident that the processes of heterotopic ossification in FOP are very similar to new born formation phenomenon in spondyloarthritis and reliable suppression of inflammation can interrupt the progression of the disease. We used similar justifications to our colleagues for the use of anti-cytokine drugs, but used a JAK-kinase inhibitor, it was extremely important the oral rout of drug administration and possibility to escape any injections in FOP. TOFA demonstrated positive effect and safety in children with severe course of FOP. It showed their advantages over the use of steroids and possibility to inhibit the rate of progression.References:[1]R.Haviv et al. Is fibrodysplasia ossificans progressiva aninterleukin-1 driven auto-inflammatory syndrome? Pediatric Rheumatology (2019) 17:84 //doi.org/10.1186/s12969-019-0386-6Disclosure of Interests:None declared.

scholarly journals Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

2021 ◽  
Vol 9 (7) ◽  
pp. 1505
Author(s):  
Claire Roger ◽  
Benjamin Louart
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Convulsive Status Epilepticus ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

scholarly journals The toxic effects of chloroquine and hydroxychloroquine on skeletal muscle: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Cristina Biguetti ◽  
Joel Ferreira Santiago Junior ◽  
Matthew William Fiedler ◽  
Mauro Toledo Marrelli ◽  
Marco Brotto
Keyword(s):  
Systematic Review ◽  
Quantitative Analysis ◽  
Qualitative Analysis ◽  
Observational Studies ◽  
Skeletal Muscles ◽  
Case Reports ◽  
Meta Analysis ◽  
Toxic Effects ◽  
Drug Induced ◽  
Qualitative And Quantitative

AbstractThe aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles. We collected data published from 1990 to April 2020 using PubMed, Cochrane Library, EMBASE, and SciELO. Risk of bias for observational studies was assessed regarding the ROBIN-I scale. Studies with less than five patients (case reports) were selected for an additional qualitative analysis. We used the software Comprehensive Meta-Analysis at the confidence level of 0.05. We identified 23 studies for qualitative analysis (17 case-reports), and five studies were eligible for quantitative analysis. From case reports, 21 patients presented muscle weakness and confirmatory biopsy for CQ/HCQ induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of CQ/HCQ, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy. No study presented randomized samples. The chronic use of CQ/HCQ may be a risk for drug-induced myopathy. There is substantiated need for proper randomized trials and controlled prospective studies needed to assess the clinical and subclinical stages of CQ/HCQ -induced muscle myopathy.

scholarly journals Anti-oxidative and antimicrobial activities of Hieracium pilosella L. extracts

2008 ◽  
Vol 73 (5) ◽  
pp. 531-540 ◽  
Author(s):  
Ljiljana Stanojevic ◽  
Mihajlo Stankovic ◽  
Vesna Nikolic ◽  
Ljubisa Nikolic
Keyword(s):  
Salmonella Enteritidis ◽  
Radical Scavenging ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Quantitative Composition ◽  
Minimal Inhibitory Concentrations ◽  
Qualitative And Quantitative ◽  
Scavenging Effect ◽  
Hieracium Pilosella ◽  
Radical Scavenging Effect

The anti-oxidative and antimicrobial activities of different extracts from Hieracium pilosella L. (Asteraceae) whole plant were investigated. The total dry extracts were determined for all the investigated solvents: methanol, dichloromethane, ethyl acetate and dichloromethane: methanol (9:1). It was found that the highest yield was obtained by extraction with methanol (12.9 g/100 g of dry plant material). Qualitative and quantitative analysis were performed by the HPLC method, using external standards. Chlorogenic acid, apigenin-7-O-glucoside and umbelliferone were detected in the highest quantity in the extracts. The qualitative and quantitative composition of the extracts depends on the solvent used. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect of the extracts was determined spectrophotometrically. The highest radical scavenging effect was observed in the methanolic extract, both with and without incubation, EC50 = 0.012 and EC50 = 0.015 mg ml-1, respectively. The antimicrobial activities of the extracts towards the bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Salmonella enteritidis and Klebsiella pneumoniae) and the fungi (Aspergillus niger and Candida albicans) were determined by the disc diffusion method. The minimal inhibitory concentrations were determined for all the investigated extracts against all the mentioned microorganisms.

scholarly journals Chemistry and Biology of Essential Oils of GenusBoswellia

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Hidayat Hussain ◽  
Ahmed Al-Harrasi ◽  
Ahmed Al-Rawahi ◽  
Javid Hussain
Keyword(s):  
Essential Oils ◽  
Current Knowledge ◽  
Biological Activities ◽  
Ethanolic Extract ◽  
Quantitative Composition ◽  
Volatile Constituents ◽  
Traditional Medicines ◽  
Qualitative And Quantitative ◽  
Synthetic Drugs ◽  
Explicit Consideration

The properties ofBoswelliaplants have been exploited for millennia in the traditional medicines of Africa, China, and especially in the Indian Ayurveda. In Western countries, the advent of synthetic drugs has obscured the pharmaceutical use ofBoswellia, until it was reported that an ethanolic extract exerts anti-inflammatory and antiarthritic effects. Frankincense was commonly used for medicinal purposes. This paper aims to provide an overview of current knowledge of the volatile constituents of frankincense, with explicit consideration concerning the diverseBoswelliaspecies. Altogether, more than 340 volatiles inBoswelliahave been reported in the literature. In particular, a broad diversity has been found in the qualitative and quantitative composition of the volatiles with respect to different varieties ofBoswellia. A detailed discussion of the various biological activities ofBoswelliafrankincense is also presented.

Platelet Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung ◽  
James L. Zehnder
Keyword(s):  
Platelet Function ◽  
Clinical Manifestations ◽  
Von Willebrand Disease ◽  
Drug Induced ◽  
Excessive Bleeding ◽  
Vascular Integrity ◽  
Patient Reports ◽  
Platelet Function Disorders ◽  
Hemorrhagic Disorders ◽  
Von Willebrand

A bleeding disorder may be suspected when a patient reports spontaneous or excessive bleeding or bruising, often secondary to trauma. Possible causes can vary between abnormal platelet number or function, abnormal vascular integrity, coagulation defects, fibrinolysis, or a combination thereof. This review addresses hemorrhagic disorders associated with quantitative or qualitative platelet abnormalities, such as thrombocytopenia, platelet function disorders, thrombocytosis and thrombocythemia, and vascular purpuras. Hemorrhagic dis­orders associated with abnormalities in coagulation (e.g., von Willebrand disease and hemophilia) are not covered. An algorithm shows evidence-based practice guidelines for the management of immune thrombocytopenic purpura. Tables list questions regarding bleeding and bruising to ask patients, clinical manifestations of hemorrhagic disorders, typical results of tests for hemostatic function in bleeding disorders, causes of thrombocytopenia, other forms of drug-induced thrombocytopenia, classification of platelet function disorders, and selected platelet-modifying agents. This review contains ­1 highly rendered figure, 7 tables, and 82 references. 

The control of the qualitative and quantitative composi-tion of vitamins and tocopherols of various types of vegetable oils

2021 ◽  
pp. 92-95
Author(s):  
Александр Николаевич Остриков ◽  
Наталья Леонидовна Клейменова ◽  
Инэсса Николаевна Болгова ◽  
Максим Васильевич Копылов ◽  
Екатерина Юрьевна Желтоухова
Keyword(s):  
Vegetable Oils ◽  
The Body ◽  
Quantitative Composition ◽  
Vitamin B ◽  
Silybum Marianum ◽  
Qualitative And Quantitative ◽  
Energy Needs ◽  
Wide Range ◽  
Cold Pressed ◽  
Vitamin Activity

Использование растительных масел в рационе человека необходимо для удовлетворения энергетической потребности организма и регулирования биологических процессов. В настоящей работе представлен качественный и количественный состав витаминов и токоферолов различных видов растительных масел, полученных холодным отжимом из выращенных в нашей стране расторопши, горчицы, подсолнечника, рыжика, рапса. Проведен сравнительный анализ литературных источников о наличии витаминов и токоферолов в различных растительных маслах. Количественный и качественный витаминный состав для одного и того же вида масла, по данным разных авторов, варьируется в достаточно широком диапазоне. В ходе исследования изучен витаминный состав пяти растительных масел. Результаты свидетельствуют, что наибольшей витаминной активностью обладают масла рыжиковое, расторопши и горчичное. Установлено наличие витамина А в маслах: рыжиковом (27,15±0,002 мкг%), расторопши (19,07±0,02 мкг%), горчичном (24,77±0,02 мкг%). Витамины В и В присутствуют в маслах горчичном, рыжиковом и расторопши; витамин В определен в горчичном и рыжиковом, В - в рыжиковом и расторопши. В маслах горчичном и расторопши присутствует витамин В. Наиболее богаты витамином Е масла рыжиковое (52,8±0,02 мг%), подсолнечное (48,3±0,02 мг%), расторопши (47,12±0,02 мг%). Витамин К и токоферолы определены во всех растительных маслах. Присутствие b-каротина обнаружено в рыжиковом (1,237±0,004 мг%), расторопши (0,812±0,002 мг%), подсолнечном (0,22±0,02 мг%) и горчичном (0,148±0,002 мг%) маслах. Анализируемые масла холодного отжима можно рассматривать как ценный источник при проектировании новых многоцелевых продуктов или побочных продуктов для промышленного, косметического и фармацевтического использования. The use of vegetable oils in the human diet is necessary to meet the energy needs of the body and regulate biological processes. This work presents the qualitative and quantitative composition of vitamins and tocopherols of various types of vegetable oils obtained by cold pressing from silybum marianum, mustard, sunflower, camelina, rapeseed grown in our country. A comparative analysis of the literature on the presence of vitamins and tocopherols in various vegetable oils has been carried out. The quantitative and qualitative vitamin composition for the same type of oil, according to different authors, varies in a wide range. During the study, the vitamin composition of five vegetable oils was studied. The results indicate that the following oils have the highest vitamin activity: camelina, silybum marianum and mustard. The presence of vitamin A was found in oils: camelina (27.15±0.002 μg%), silybum marianum (19.07±0.02 μg%), mustard (24.77±0.02 μg%). Vitamins B and B are present in mustard, camelina and silybum marianum oils; vitamin B is found in mustard and camelina; B in camelina and silybum marianum. Mustard and silybum marianum oils contain vitamin B. The richest in vitamin E are camelina (52.8±0.02 mg%), sunflower (48.3±0.02 mg%), silybum marianum (47.12±0.02 mg%). Vitamin K and tocopherols are found in all vegetable oils. The presence of b-carotene was found in camelina (1.237±0.004 mg%), silybum marianum (0.812±0.002 mg%), sunflower (0.22±0.02 mg%) and mustard (0.148±0.002 mg%) oils. The analyzed cold-pressed oils can be considered as a valuable resource when designing new multipurpose products or by-products for industrial, cosmetic and pharmaceutical applications.

scholarly journals Axitinib and HDAC Inhibitors Interact to Kill Sarcoma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Jane L. Roberts ◽  
Laurence Booth ◽  
Andrew Poklepovic ◽  
Paul Dent
Keyword(s):  
Hdac Inhibitor ◽  
Kinase Inhibitor ◽  
Hdac Inhibitors ◽  
Autophagic Flux ◽  
Drug Induced ◽  
Ampk Signaling ◽  
Knock Down ◽  
Reduce Tumor Growth ◽  
Sarcoma Cells

We have extended our analyses of HDAC inhibitor biology in sarcoma. The multi-kinase inhibitor axitinib interacted with multiple HDAC inhibitors to kill sarcoma cells. Axitinib and HDAC inhibitors interacted in a greater than additive fashion to inactivate AKT, mTORC1 and mTORC2, and to increase Raptor S722/S792 phosphorylation. Individually, all drugs increased phosphorylation of ATM S1981, AMPKα T172, ULK1 S317 and ATG13 S318 and reduced ULK1 S757 phosphorylation; this correlated with enhanced autophagic flux. Increased phosphorylation of ULK1 S317 and of Raptor S722/S792 required ATM-AMPK signaling. ULK1 S757 is a recognized site for mTORC1 and knock down of either ATM or AMPKα reduced the drug-induced dephosphorylation of this site. Combined exposure of cells to axitinib and an HDAC inhibitor significantly reduced the expression of HDAC1, HDAC2, HDAC3, HDAC4, HDAC6 and HDAC7. No response was observed for HDACs 10 and 11. Knock down of ULK1, Beclin1 or ATG5 prevented the decline in HDAC expression, as did expression of a constitutively active mTOR protein. Axitinib combined with HDAC inhibitors enhanced expression of Class I MHCA and reduced expression of PD-L1 which was recapitulated via knock down studies, particularly of HDACs 1 and 3. In vivo, axitinib and the HDAC inhibitor entinostat interacted to significantly reduce tumor growth. Collectively our findings support the exploration of axitinib and HDAC inhibitors being developed as a novel sarcoma therapy.

scholarly journals Drug-Induced Heart Failure (Part 2: Mechanisms of Development, Clinical Signs, Differential Diagnosis, Risk Factors, Treatment and Prevention)

2020 ◽  
Vol 8 (2) ◽  
pp. 57-65
Author(s):  
O. D. Ostroumova ◽  
I. V. Goloborodova
Keyword(s):  
Heart Failure ◽  
Beta Blockers ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Channel Blockers ◽  
Drug Induced ◽  
Treatment And Prevention ◽  
Developing Heart

Heart failure is a complex clinical syndrome caused by an impaired pumping function of the heart muscle, etiologically associated with cardiovascular disease and, in the vast majority of cases, requiring complex therapeutic regimens and simultaneous prescription of several drugs. To date, we know several classes of drugs (including those used for heart failure) which can induce development/progression of heart failure in both patients with left ventricular dysfunction, and in patients who do not have cardiovascular diseases. The aim of the study was to analyse and systematize data on development mechanisms, as well as methods of prevention and treatment of drug-induced heart failure when using diff erent groups of drugs. It has been established that drug-induced heart failure is most often associated with the use of calcium channel blockers (verapamil, diltiazem, nifedipine), beta-blockers, antiarrhythmic drugs (disopyramide, fl ecainide, propafenone, amiodarone, ibutilide, dofetilide, dronedarone), anthracyclines (doxorubicin) and other antitumor drugs (trastuzumab, bevacizumab, infl iximab), hypoglycemic drugs (thiazolidinediones, saxagliptin, alogliptin), and nonsteroidal anti-infl ammatory drugs, including selective cyclooxygenase-2 inhibitors. The study revealed various mechanisms of heart failure development following drug treatment. In some patients, heart failure development is associated with the cardiotoxic eff ect of a particular drug, in others with adverse eff ects on hemodynamics. Much depends on risks of developing heart failure, including specifi c risks attributable to groups of drugs and individual drugs. The identifi cation of drugs that can contribute to the development/ progression of heart failure, and possible clinical manifestations of drug-induced heart failure, as well as provision of timely information to physicians, and engagement of clinical pharmacologists with the aim of optimizing treatment of patients can facilitate timely diagnosis, treatment and prevention of drug-induced heart failure. 

Sign in / Sign up

Export Citation Format

Share Document