New Potential Beta-3 Adrenergic Agonists with Beta- Phenylethylamine Structure, Synthesized for the Treatment of Dyslipidemia and Obesity

Beta-3 adrenergic receptors have important physiological implications, being expressed in many places in the body, including brown adipose tissue. Of the effects studied in preclinical research on lipid metabolism attributable to stimulation of these receptors, we can mention the increased thermogenesis and metabolic rate in the brown adipose tissue, reduction of body weight in obese diabetic rats, lowering of intra-abdominal and subepithelial fat in nonobese and nondiabetic rats, decrease of triglyceride, and increase of HDL cholesterol levels. Carbohydrate metabolism is also changed by beta-3 adrenergic agonists, the most prevalent effects being blood glucose lowering in diabetic rats, increasing insulin secretion of the pancreas, or increasing glucose tolerance. Metabolic effects of 13 newly synthesized compounds of beta-phenylethylamine structure and reference BRL 37344 were investigated in order to identify a potential affinity for beta-3 adrenergic receptors. The antidiabetic and hypolipemiant effects were investigated on a rat model of alloxan-induced diabetes. The results demonstrated that new beta-phenylethylamine derivatives produced marked biological activity over lipid profile. All compounds have markedly decreased the values of total cholesterol, LDL cholesterol, and triglycerides and also have increased the values of antiatherogenic HDL cholesterol. The effects were significantly more intense than the reference substance BRL 37344

Исследование антибиотикотерапии в коммунитарных аптеках в Румынии

Disciplina Farmacologie şi Farmacie clinică, Facultatea Farmacie, Universitatea de Medicină şi Farmacie Carol Davila, Bucureşti, RomâniaAntibioticele şi chimioterapicele antimicrobiene reprezintă unele dintre cele mai cunoscute şi mai utilizate medicamente. Notorietatea lor şi insuficienta inţelegere a mecanismelor de acţiune determină tot mai mulţi pacienţi să le folosească pentru tratarea tusei, răcelii comune sau chiar durerii [6]. In multe cazuri, chiar prescrierea de antibiotice este neadecvată [3]. Astfel, antibioticele sunt adesea prescrise fără a exista confirmarea unei infecţii de origine bacteriană sau fără să existe motivul unui tratament profilactic. Cunoaşterea agentului infecţios in vederea stabilirii substanţei active potrivite, a dozei corecte, a căii de administrare şi a duratei tratamentului este absolut necesară pentru a putea institui o antibioterapie ştiinţifică şi raţională [1, 4]. Utilizarea inadecvată a antibioticelor poate duce la reacţii adverse, toxicitate de organ, suprainfecţie cu microorganisme rezistente, precum Clostridium difficile sau Pseudomonas aeruginosa [5].Antibiotics and antimicrobial chemotherapeutic drugs are among the best known and most used drugs. This notoriety and the insufficient knowledge of their mechanism of action lead more and more patients to use them in the treatment of the common cold cough or even pain [6]. In many cases, the prescription itself of antibiotics is inadequate [3] as it often occurs without the confirmation of a bacterial infection or without a real need of a prophylactic treatment. Knowing the infectious agent in order to determine the appropriate active substance, the correct dosage, the administration path and the length of treatment is essential for establishing a scientific and rational antibiotherapy [1, 4]. Inadequate use of antibiotics may lead to side effects, organ toxicity, over infection with highly resistant microorganisms such as Clostridium difficile or Pseudomonas aeruginosa [5].Антибиотики и противомикробные препараты являются одними из самых популярных и наиболее часто используемых препаратов. Их новаторство и неадекватное понимание механизмов действия заставляют все больше пациентов использовать их для лечения кашля, простуды или даже боли [6]. Во многих случаях даже выписывание антибиотиков неадекватное [3]. Таким образом, антибиотики часто назначают без подтверждения инфекции бактериального происхождения или без причины профилактического лечения. Определение инфекционного агента для установления правильного активного вещества, правильная доза, путь введения и продолжительность лечения абсолютно необходимы для установления научной и рациональной антибактериальной терапии [1, 4]. Неправильное использование антибиотиков может привести к неблагоприятным реакциям, органной токсичности, суперинфекции с устойчивыми микроорганизмами, такими как Clostridium difficile или Pseudomonas aeruginosa [5]

Synthesis and Pharmacological Research Regarding New Compounds with Quinazolin-4-One Structure

The quinazoline scaffold is found in the chemical structure of many marketed drugs used in CNS disorders as antidepressants, anxiolytics, or hypnotics. Also, the carbamate ester derivatives have different certain therapeutic actions, such as hypnotic or parasympathomimetic ones. We have obtained new 4(3H)-quinazolinones by bringing together in the same structure the quinazoline nucleus and carbamate ester group. The compounds named Q1–Q5 were characterized by measuring the melting points, by determining the infrared and NMR spectra, and by elemental analysis. The pharmacological tests evidenced that the compounds have a very low acute toxicity, lethal doses being >2000 mg/kg bw. The compounds had different actions observed in forced swimming test (FST), tail suspension test (TST), or elevated plus maze (EPM), probably influenced by the presence of different radicals on the nucleus. Thus, Q1 with a nitro group in structure manifested the highest antidepressant effect, showing a reduction of immobilization time in FST and TST. On the other hand, Q3 and Q5, with two groups methoxy, respective ethoxy, had a slight anxiolytic effect, highlighted by an increase of the time spent in open arms and a decrease of the time spent in closed arms of EPM

Фармакологические экспериментальные исследования побочных эффектов ассоциации алпразолам+бромазепам

Disciplina Farmacologie şi Farmacie clinică, Facultatea Farmacie, UMF Carol Davila, Bucureşti, RomâniaIn lucrarea de faţă ne-am propus cercetarea preclinică a potenţialului farmacotoxicologic al asocierii dintre două benzodiazepine: alprazolam şi bromazepam. Cercetările noastre s-au efectuat la şoareci prin teste farmacologice specifice de evaluare a efectului miorelaxant (testul rotarod) şi a efectului asupra memoriei şi achiziţiei spaţiale (labirintul acvatic Morris). Dozele administrate au fost. alprazolam 0,5 mg/kg corp şi bromazepam 0,75 mg/kg corp. In urma cercetărilor efectuate, putem afirma că cele două benzodiazepine studiate, alprazolam şi bromazepam, la dozele administrate, singure sau in asociere, nu influenţează in sens negativ abilitatea şoarecilor de a se menţine pe axul in rotaţie sau capacitatea de a invăţa şi de a memora poziţia platformei in testul labirintului acvatic Morris.In the present paper we have researched, through experimental pharmacology studies, the pharmacotoxicological potential of the association between two benzodiazepine drugs: alprazolam and bromazepam. Our research has performed using specific pharmacological tests to evaluate the effect of miorelaxant (rotarod test) and effect on memory and spatial acquisition (Morris aquatic labyrinth). The doses administered were alprazolam 0.5 mg/kg body weight and bromazepam 0.75 mg/ kg body weight. Based on our research, we can state that the studied benzodiazepines, alprazolam and bromazepam, at the doses administered alone or in combination, do not adversely affect the ability of mice to maintain on the rotating spindle or the ability to learn and to remember platform position in the Morris aquatic labyrinth test.В этой статье мы поставили себе цель провести доклинические исследования фармакотоксикологического потенциала ассоциации между двумя бензодиазепинами: альпразоламином и бромазепамом. Наши исследования проводились на мышах с помощью специфических фармакологических тестов для оценки влияния миорелаксанта (тест ротарода) и влияния на память и пространственное поглощение (водный лабиринт Морриса). Доза альпразолама была 0,5 мг/кг массы тела и бромазепа – 0,75 мг/кг массы тела. Основываясь на наших исследованиях, мы можем констатировать, что два исследуемых бензодиазепина, альпразолам и бромазепам в указанных дозах, вводимых отдельно или в комбинации, не оказывают отрицательного влияния на способность мышей поддерживать ось вращения или способность учиться и помнить позицию платформы в тесте водного лабиринта Морриса

Pharmacist involvement for increased adherence to chronic treatment

Disciplina de Farmacologie şi Farmacie clinică, Facultatea de Farmacie, UMF ’’Carol Davila” Bucureşti, Spitalul Universitar de Urgenţă BucureştiIntroducere. Nerespectarea prescripţiei medicale de către pacient a reprezentat întotdeauna o cauză importantă a insuccesului terapeutic dar şi a creşterii costurilor pentru sănătate. în 1976, Sackett a introdus pentru prima dată termenul de complianţă în medicină, concept care includea respectarea recomandărilor făcute de personalul medical, fără existenţa unui parteneriat medic/pacient. în 1993 apare noţiunea de aderenţă la tratament, concept care înglobează mai mulţi termeni moderni: concordanţă, cooperare, parteneriat, între pacient şi medicul curant. Scopul studiului. Am urmărit determinarea gradului de aderenţă al pacienţilor din România aflaţi în tratament cronic pentru hipertensiune arterială şi pentru scleroză multiplă, identificând şi cauzele posibile ale non aderentei la tratament. Intervenţia farmacistului 9 9 pentru corectarea comportamentului non aderent la medicaţie a constat în programarea unor vizite de consiliere privind terapia hipertensiunii arteriale pentru pacienţii arondaţi farmaciilor de comunitate şi în crearea unei platforme on line pentru pacienţii cu scleroză multiplă, în care aceştia pot adresa întrebări legate de patologie, eficacitate şi siguranţă a tratamentului. Material şi metode. Pentru determinarea gradului de aderenţă la tratamentul antihipertensiv am utilizat Scala Morisky iar pentru pacienţii cu scleroză multiplă am utilizat Chestionarul de Aderenţă la Tratament în Scleroza Multiplă (MSTAQ). Rezultate. în studiul efectuat în farmaciile de comunitate dintr-n total de 581 pacienţii intervievaţi 41,99% au fost bărbaţi şi 58,00% femei. Patologiile cel mai frecvent identificate în populaţie au fost: 72,11% hipertensiune arterială, 43,02% dislipidemie şi 20,30% diabet zaharat. Pacienţii din colectivitatea intervievată au avut un număr mediu de 4,6 mediamente pe zi alături de un consum de 1,9 suplimente alimentare. Gradul de aderenţă mediu pe acest eşanton de populaţie a fost de 5,63 ceea ce îi încadrează în rată de aderenţă joasă conform scalei Morisky. în cazul pacienţilor cu scleroză multiplă s-au analizat retrospectiv 75 de cazuri, dintre acestea 35 de pacienţi fiind trataţi cu glatiramer acetat, iar 40 cu interferon beta- la. Pentru pacienţii trataţi cu glatiramer acetat (în medie 7,8±4,1 ani) s-au obţinut următoarele date: media de vârstă a pacienţilor în anul 2016 a fost de 39,14±8,5 ani, scorul de dizabilitate (EDSS) stabilit la diagnosticare a fost 1,5±1,1 iar scorul actual de dizabilitate 2,3±1,1. Dintre pacienţii trataţi cu glatiramer acetat, un procent de 42,85% au avut o creştere a scorului de dizabilitate cu 148,44%. Pentru pacienţii trataţi cu interferon beta-la (în medie 5,8±4,6 ani) s-au obţinut următoarele date: media de vârstă a pacienţilor în anul 2017 a fost de 41,49±11,84 ani, scorul de dizabilitate (EDSS) stabilit la diagnosticare a fost 1,7±1,4 iar scorul actual de dizabilitate 2,5±1,9. Dintre pacienţii trataţi cu interferon beta-la, un procent de 25% au avut o creştere a scorului de dizabilitate cu 100%. Concluzii. Implicarea farmacistului clinician din farmacia de comunitate în consilierea pacienţilor privind medicaţia prescrisă, medicaţia OTC şi consumul de suplimente alimentare, a interacţiunilor medicament/medicament, medicament/aliment sau supliment alimentar este esenţială pentru creşterea gradului de aderenţă al bolnavilor cu patologii cronice. De asemenea, intervenţia farmacistului clinician din spital în analiza evoluţiei progresiei bolii şi în consilierea pacienţilor cu scleroză multiplă asupra importanţei tratamentului ar putea creşte calitatea vieţii acestora.Introduction. Disobeying medical prescription by the patient has always represented an important cause of therapeutical failure and also of increased health expenditures. In 1976 Sackett introduced for the first time the term of compliance in medicine, a concept which included observance to the recommendations made by the medical staff without implying a physician/patient partnership. In 1993, the notion of adherence to treatment appears, a concept that encompasses more modem terms: accordance, cooperation, partnership between patient and attending physician. The aim of the study. To determine the degree of adherence for Romanian patients under chronic treatment for arterial hypertension and multiple sclerosis, eventually identifying the probable causes of non-adherence to treatment. Involving the pharmacist in adjusting the non-adherent behavior consisted in scheduling visits of counseling on therapy of arterial hypertension for the patients allocated to community pharmacies and in creating an online platform for multiple sclerosis patients on which questions concerning disease pathology, efficacy and safety of treatment. Material and methods. In order to determine the degree of adherence to antihypertensive treatment Morisky Scale was used while for the multiple sclerosis the Multiple Sclerosis Treatment Adherence Questionnaire (MSTAQ) was used. Results. In the study performed in community pharmacies, out of a total of 581 interviewed patients, 41.99% were men and 58.00% were women. The most frequent pathologies identified in population were as follows: arterial hypertension 72.11%, dyslipidemias 43.02% and diabetes mellitus 20.30%. The patients in the interviewed collective had an average of 4.6 drugs per day, together with an adjacent consumption of 1.9 nutritional supplements. The average degree of adherence in this population sample was 5.63 which appoints them to low adherence rate according to Morisky scale. In the case of multiple sclerosis patients, a number of 75 cases were retrospectively analyzed, out of which 35 were being treated with glatiramer acetate and the other 40 with interferon beta-la. For the ones treated with glatiramer (mean time of treatment 7.8±4.1 years), the following data were obtained: average age in 2016 was 39.14±8.5 years, mean disability score (EDSS) established at the time of diagnosis was 1.5±1.1 and actual mean disability score was 2.3±1.1. A percentage of 42.85% of the patients treated with glatiramer manifested increased mean disability score by 148.44%. For the ones treated with interferon beta-la (mean time of treatment 5.8±4.6 years), the following data were obtained: average age in 2017 was 41.49±11.84 years, mean disability score established at the time of diagnosis was 1.7±1.4 and actual mean disability score was 2.5±1.9. A percentage of 25.00% of the patients treated with interferon beta-la manifested increased mean disability score by 100.00%. Conclusions. The involvement of clinical pharmacist from the community pharmacy in counseling the patients on the prescribed medications, OTC drugs and consumption of nutritional supplements, on the interactions between drugs, between drugs and food or nutritional supplements is essential in order to increase the degree of adherence for the patients with chronic disease. Moreover, the intervention of the clinical pharmacist in hospital setting on analysis of disease progression and counseling multiple sclerosis patients over the importance of treatment might improve their quality of life

Non-clinical toxicity and phytotoxicity of two herbal extracts

University of Medicine and Pharmacy “Carol Davila” Bucharest, Faculty of Pharmacy, Department of Pharmaceutical Botany and Cell Biology University of Medicine and Pharmacy “Carol Davila” Bucharest, Faculty of Pharmacy, Department of Pharmacology, Bucharest, Romania State University of Medicine and Pharmacy “Nicolae Testemiţanu”, Faculty of Pharmacy, Department of Pharmacognosy and Pharmaceutical Botany, Chisinau, Republic of Moldov