Cyclic voltammetry as a sensitive approach in investigation of doxorubicin

Introduction and objective Doxorubicin is an anthracycline drug. Its chemotherapeutic effect is due to two possible mechanisms, 1)disruption of topoisomerase-II-mediated DNA repair due to its intercalation into DNA helix and 2)generation of free radicals and their damage to cellular membranes, DNA, and proteins. This can be a result of its planar aromatic chromophore which intercalates between two base pairs of DNA [1]. Therefore, its pharmacological/toxicological characteristics are largely dependent on its oxidative properties, and the aim of this study is to summarize the methods and data based on its еlectrochemical behavior of doxorubicin, obtained by the means of cyclic voltammetry (CV) [2]. Methods Cyclic voltammetry is a versatile electrochemical method where the redox reactions occurring at the working electrode result in a flow of current. The potentiostat measures this current and plots it as a function of the applied potential. Each successful forwards and backwards potential sweep produces a a cyclic voltammogram characterized by anodic and cathodic peak currents, peak potentials, and the oxidation and reduction onset potentials. Results Our research revealed several studies that feature the electrochemical behavior of doxorubicin. CV in pH~7.4 has shown that doxorubicin undergoes a reversible two-electron reduction with value E1/2 = -665 mV(versus Ag/AgCl, saturated KCl). This process was defined as quasi reversible, at low scan rates. Further, the interaction of doxorubicin hydrochloride with calf thymus DNA was studied by measuring cathodic peak current, which gradually decreased as more DNA was added into the cell [3]. The interaction of doxorubicin with calf thymus DNA, was mostly assessed by electrochemical sensors using surface modified working electrodes [4,5,6]. Electrochemical sensor based on multi-walled carbon nanotubes modified platinum electrode (Pt/MWCNTs) [4], electrodeposition of silver nanoparticles and electro-polymerization of alginate layers on the surface of a glassy carbon electrode have been also used in this purpose [5]. CV of doxorubicine on a screen-printed electrodes modified with single-wall carbon nanotubes (SPE/CNT) have shown linear dependence of the intensity of electro reduction/oxidation on the square root of the scan rate which proved that the process is a controlled by diffusion. Moreover, thay imployed differential pulse voltammetry to validate a sensitive method for doxorubicine quantification. The drug binding processes were examined by DPV via the registration of a decrease in peak current intensity of guanine, adenine, and thymine of DNA in the presence of doxorubicin [6]. Conclusion Cyclic voltammetry can be used as an efffective tool for quantification of doxorubicine and its interactions with DNA or other metals. Reverible oxidation of doxorubicin to semiquinone and back, releases reactive oxygen species that cause DNA damage and lipid peroxidation. The effectivness of the therapeutic effect of doxorubicine depends on its interaction with DNA. These interactions were mostly assessed by using an electrochemical surface modified sensor, in the presence of DNA. These data lead to a conclusion that electrochemical platforms represent a sensitive approach for the investigation of DNA–drug interaction in electrode systems. Examining the electrochemical signals doxorubicin or DNA–doxorubicin complex before and after binding establishes the interaction and helps in mechanism elucidation

Clinically significant drug interactions of Eltrombopag: a retrospective study from the clinical pharmacist perspective

Introduction: Thrombopoietin is the main cytokine regulating megakaryopoiesis and platelet production. Eltrombopag interacts with the transmembrane domain of thrombopoietin receptors and initiates signaling cascades inducing proliferation and differentiation from bone marrow progenitor cells. The aim of the study was to determine drug interaction at patients that are receiving Eltrombopag along with other medications. Materials and methods: A retrospective, longitudinal study was conducted at the Hematology Clinic in Skopje, N. Macedonia. A clinical pharmacist, focusing on Eltrombopag and concomitant medications interactions, reviewed a total number of 16 patient’s histories for the period of 6 months (January-June 2023). Anamnestic data on additional drugs, herbal supplements, vitamins, minerals were also taken. Potential drug interactions were identified using Stockley's interactions checker, categorized by severity and subclassified into co-administered drugs altering pharmacokinetics. Results: A total number of 73 interactions were identified, of which 23 (31.51%) were with moderate clinical relevance, 14 (19.18%) were with no clinical importance and required counseling about possible adverse effects and additional monitoring. The rest of 36 (49,32%) interactions were without clinical significance. Additionally, we determine that 7 (9.59%) of total interactions directly related to patients receiving Eltrombopag (ciclosporin, atorvastatin, rosuvastatin, dexamethasone, prednisolone, valsartan, and magnesium) and categorized as moderate and needs close monitoring. Conclusion: This study demonstrates toxicity potential of Eltrombopag at patients associated with concomitant medicines. Close collaboration of physicians and clinical pharmacists is necessary in all cases where patients are receiving Eltrombopag along with other medications in order all significant interactions to be identified, prevented and managed

Determination of non-adherence in patients receiving Eltrombopag

Eltrombopag, an orally administered thrombopoietin receptor agonist, selectively binds to the transmembrane domain of the thrombopoietin receptor on the surface of platelets, megakaryocytes and megakaryocyte precursor cells (1). The aim of our research is to determine patient non-adherence and its impact on the effectiveness and safety of prescribed therapy, as well as the possibility of treatment failure. The observational, longitudinal, and retrospective study was conducted in the PHO University Clinic of Hematology in Skopje, R.N.Macedonia. 17 patients (9 men and 8 women) were followed from January to August 2023. Five of them were with diagnose aplastic anemia and 12 with immune thrombocytopenia. All of them treated with Eltrombopag. We have systematically reviewed medical records from the Department of Hospital pharmacy, collected anamnestic data and determine non-adherence to therapy, followed by dose frequency, double taking therapy, omitted doses, drug-drug interactions and food/supplement-drug interactions. Thirteen types of non-adherence were identified, of which 3(23,08%) were related to dose frequency, 1(7,69 %) was related to double taking therapy, 5(38,46%) were related to the possibility of drug-drug interactions, 2(15,38%) with possibility for food/supplement-drug interactions and 2(15,38 %) were related with omitted doses. Failure to adherence is a serious problem which not only affects the patient but also the health care system. The clinical pharmacist intervention can improve patient adherencе, because the most important determinants effectiveness and safety are adherence to the prescribed therapy, multiple drug and food/supplement interactions which can vary on dose-response relationship, and risk of insufficient effectiveness of therapy (2)

Безбедност на пациентите во клиничка пракса - програма за контролиран пристап до лекот леналидомид

Леналидомид е лек кој поседува антинеопластично, антиангиогено, проеритропоетско и имуномодулаторно дејство, но притоа поседува и изразено тератогено дејство. Клиничкиот фармацевт при ЈЗУ Универзитетска клиника за хематологија - Скопје е одговорен за спроведување на процесот на фармаковигиланца. Затоа, со цел подобрување на безбедноста на пациентите, на клиниката се спроведе контролирана дистрибуција на лекот таблети леналидомид од 5 mg. Kако мерка за минимализација на ризикот (ММР) за пациентите кои го примаат овој лек се спроведе програмата за контролиран пристап (CAP), според која пропишувањето на лекот го вршат исклучиво лекари кои се евидентирани во Регистарот на едуцирани лекари за спроведување на програмата за превенција на бременост (PPP). Со тоа се водеше грижа пациентот да го прими лекот само доколку се исполнети барањата од PPP. Бидејќи лекот се излачува и во спермата, во програмата покрај жени мораше да бидат вклучени и пациенти од машка популација. За лекот таблети леналидомид 5 mg, PPP е спроведена кај 36 пациенти (23 мажи и 13 жени), во тек на 18 месеци, започнувајќи од октомври 2021 година. Вo овој период лекот е издаден на 14 пациенти со мултипен миелом кои претходно примиле барем една линија на терапија (во комбинација со дексаметазон), 22 пациенти со терапија на одржување на новодијагностициран мултипен миелом кај кои е спроведена трансплантација на автологни матични клетки и 1 пациент со дијагноза Не-Хочкинов фоликуларен лимфом. Со едуцирање на пациентите и преземање на сите пропишани мерки од PPP, потенцијалниот ризик од тератогеното дејство на лекот беше сведен на минимум

Технолошки пристап во производството на стандардизиран екстракт од канабис базиран на канабинол (CBN) за медицински цели

Канабинолот (CBN) се добива со деградација на тетрахидроканабинол (ТНС), кога производот од канабис е изложен на топлина или подлежи на стареење. CBN е благ психоактивен канабиноид кој делува како слаб парцијален агонист со афинитет кон CB1 рецепторите. Докажани се неговите седативни, антиинфламаторни и невропротективни својства. За да се произведе стандардизиран екстракт базиран на CBN, потребно е да се изврши присилна деградација или забрзано стареење на ТНС, со цел распаѓање до неговиот метаболит CBN. За таа цел беше применет процес на деградација на ТНС по забрзано стареење на етанолен екстракт со 32,8% (w/w) THC и 7,4% (w/w) CBN и последователно негова молекуларна дестилација, со цел концентрирање на CBN. Притоа, искористивме етанолен екстракт од Glueberry OG кој беше подлегнат на студија за забрзано стареење од една година. Опремата и методите опфаќаат процеси на деградација на висока температура и молекуларна дестилација. Примероците беа испитувани со помош на HPLC метод со UVдетектор. По студијата за забрзано стареење, екстрактот содржи 9,7% (w/w) ТНС и 36,2% (w/w) CBN. По деградација на екстрактот, не е детектиран ТНС, а CBN се зголемил до 43,1% (w/w). Финалниот производ по молекуларна дестилација содржи 55,8% (w/w) CBN. Резултатите укажуваат дека овој метод е погоден за добивање на екстракти со задоволителен принос на CBN. Примената на покачена температура врз екстрактот може лесно да го оксидира THC во CBN. Оваа технологија може да вклучи и употреба на гасови, кислород или азот, вклучувајќи опрема за барботирање со гасови

Monitoring the safety of nilotinib in patients with chronic myeloid leukemia

The aim of the study was to evaluate the safety profile of nilotinib administered to chronic myeloid leukemia (CML) at patients. The study was conducted from March 2018 to May 2019 and it included 20 patients with CML in chronic phase. Of these 20 patients, 17 had previously been treated with imatinib and 3 with hydroxyurea. The mean duration of treatment with Nilotinib was 6.75 months. In nine patients treated with nilotinib (400 mg), 55% complained of fatigue, 33% of headache and 22.2% of pruritus. In five patients treated with Nilotinib (600 mg), 20% complained of headache, 40% of fatigue and 20% of pruritus. In addition, in six patients treated with nilotinib (800 mg), 50% complained of headache and fatigue, 17% with pruritus and visual disorder was observed in 20% of cases. In the study, the adverse reactions were observed between the age of 20 and 40 and it was 7.1%, in contrast to the group of patients between the age of 40 and 60 where the incidence of adverse reactions was 21.42%. The incidence of adverse reactions in patients in the age group over 60 years it was 57.1%. In terms of gender, the incidence of adverse reactions was equal to 50% for both men and women. In conclusion, this study showed that treatment with nilotinib was well tolerated, with adverse reactions of an easy degree. Future evaluation is necessary in order to understanding the adverse reaction of nilotinib in comparison with other tyrosine kinase inhibitors. Keywords: nilotinib, pharmacovigilance, safety, chronic myeloid leukemi