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- ItemSynthesis, Characterization, and In Vitro Conversion Kinetics of Novel Atorvastatin Prodrugs(Al-Quds University, 2022-12-20) Buthaina Amjad Taleb Al-Jubeh; بثينة أمجد طالب الجعبةHypercholesterolemia is a risk factor for the development of atherosclerotic disease. Atorvastatin is a mainstay in the prevention and treatment of hypercholesterolemia and atherosclerotic cardiovascular disease. Atorvastatin efficiently lowers increased plasma cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Due to significant presystemic metabolism, atorvastatin has low oral bioavailability (14 %). By transiently modifying the structure of a substance via prodrug synthesis, low bioavailability, and other pharmacokinetic and/or physicochemical disadvantages, can be resolved. The synthesis of novel atorvastatin prodrugs as possible candidates for atorvastatin delivery with improved bioavailability and fewer side effects is described in this thesis. Based on Bruice's enzyme model of intramolecular reactions, three atorvastatin prodrugs were synthesized in high yield by conjugating dicarboxylic anhydride linkers (maleic anhydride, succinic anhydride, and phthalic anhydride) to the hydroxyl groups of atorvastatin; in order to create prodrug systems with intramolecular hydrolysis ability. The prodrugs are expected to have greater bioavailability, because they hide the metabolically labile functional groups, and increased water solubility. Melting point, FT-IR, LC-MS, and 1H-NMR analyses were used to confirm the identity of the produced prodrugs. The intramolecular hydrolysis of the three prodrugs in different media was studied in vitro and found to have varying conversion rates or no conversion. The prodrug containing the maleate linker (proD1) was completely hydrolyzed in 0.1N acid solution, pH 3 buffer, and human plasma, at half-lives of 102 hours, 161 hours, and 198 hours, respectively. The succinate-linked prodrug (proD2) was degraded in acidic medium exclusively (pH 3) and had a half-life of 216 hours. The pH of the medium influenced prodrug intraconversion, which was quicker in acidic conditions. Furthermore, prodrug intraconversion was dependent on the structural characteristics of the connected prodrug linker, iii and the intramolecular reaction was achieved in a strained prodrug system with a favorable proximity orientation.
- ItemEEffect of Pharmaceutical Marketing Practice on Physicians’ Prescribing Behavior in the Gaza Strip(Al-Quds University, 2021-06-10) Rafat Subhi Abd Elftah Aburedwan; رأفت صبحي عبد الفتاح أبو رضوانPharmaceutical Companies (PCs) are using different marketing activities to influence physicians’ prescribing behavior. However, the interaction between physicians and PCs is a real leading factor for conflicts of interest that negatively impact physician prescribing behaviors worldwide. The aim of this study is to identify the effect of pharmaceutical marketing practice on physicians’ prescribing behavior in the Gaza Strip (GS). To fulfill the aim of the study, the researcher followed a mixed approach that utilizes quantitative and qualitative data. For quantitative data, a cross-sectional, descriptive-analytical survey was utilized among specialist physicians working in the governmental hospitals as well as the private hospitals and clinics in the GS in 2020. A self-administered well-structured questionnaire was used. For the qualitative part, focus groups and in-depth interviews were used for data collection from physicians, pharmacists, and pharmaceutical medical representatives (PMRs). Data were analyzed using SPSS. The questionnaire response rate is 91.3% (347 returned questionnaires) was achieved. This study revealed that many physicians prefer the internet (82.4%) the medical, textbooks (80.2%), and academic journals (74%) as sources of drug information rather than commercial sources of medical information However, nearly (64.2%) of physicians depend on detailing as a source of drug information. Also, 70.8%, 68.6% of physicians agreed on the importance and credibility of information provided through PMRs about the new and old drugs respectively. Results highlighted the complex correlated factors that impact physicians’ prescription behavior. These factors were categorized into drug characteristics (80.1%), organizational factors (79.1%), physician factors (75.8%), patient contexts (69.3%), and the least influential factor was pharmaceutical company factors (59.9%). However, results showed that there is an active interaction between physicians and the PCs. Findings revealed that 96% of the study sample had been visited by PMRs at least once a month. Almost all of the physicians (98.3%) received at least one of the marketing tools offered by (PCs). PMRs detailing has become prevalent in health facilities in the GS with 96.2% of physicians received skillful detailing. The provision of promotional printed material (95.7%), free medical samples (93.9%), and inexpensive gifts (74.6%) were the major prescribing inducement tools used by PMRs. The study results revealed that the current marketing tools have a considerable effect on drug choice decisions (64.2%), motivating physicians to prescribe promoted drugs (65.2%) and new drugs (66.8%). However, the influence of these tools was not similar in their effect. The most effective tools used were detailing and discussions with PMRs (73.4%). The following characteristics were significantly associated with the effect of pharmaceutical marketing on physicians’ prescription behavior: age, years of practice, average monthly income, income satisfaction, graduation country of bachelor. Also, results confirm that physicians (61.73%) are prepared to implement regulations and ethical codes that govern physicians – PMRs interactions. In conclusion, there is an active interaction between physicians and the pharmaceutical industry in the GS in both private and public sectors. These interactions had a considerable role in affecting physicians’ prescription behavior. An agreed drug prescribing policy, as well as a comprehensive guideline for physicians’ interactions with pharmaceutical companies along with follow-up mechanisms for its enforcement, should be created. Also, should promote the concept of essential drug list of medicines and developing clear protocols and guidelines and applying them. Also establish comprehensive formal training courses for physicians on their prescribing behavior. Promoting the concept of rational use of medicines and developing protocols and guidelines and enforcing them.
- ItemAssesment of Beliefs about Medicines and Adherence among Patients withSchizophrenia at the Primary Care Unit in Ramallah, Palestine(Al-Quds University, 2020-06-06) Aroub Salman Mohammad Salman; عروب سلمان محمد سلمانObjectives and background: Schizophrenia is a serious mental illness that needs more attention to be paid for. It affects how patients think, feel and behave. The exact causes underlying the problem is still unknown, but a number of risk factors can be identified including genes and environment. The aims of this study were to assess medication adherence to antipsychotic medications and to measure patients’ beliefs about their treatment necessities and concerns, which contribute to their antipsychotics adherence and treatment efficacy.Methodology: One hundred and thirty patients were recruited from the governmental psychiatry clinic in Ramallah in a cross sectional study. The self-reported Morisky-Green-Levine (MGL) scale was used to measure patients’ adherence. Beliefs about medicines questionnaire (BMQ) was used to measure beliefs about medicines.Results: The result in this study indicated that 53.8 % of the sample participants were classified as low-adherent while 46.2% of patients classified as high adherent. The majority of the patients (66.3%) had strong beliefs and necessity in their medications to maintain their good health, more than half of patients (55.4%) were concerned about becoming dependent upon antipsychotics and long-term side effects. The mean score of specific necessity scale of 16.9 (CI 95%, 15.9 - 17.9) and mean score of specific concerns scale of 16.5 (CI 95%, 15.4 - 17.6; P<0.001) were significantly correlated to medication adherence, and the mean of necessity–concern differential was 2.1 (CI 95%, 2.5 – 1.7; p <0.11) . (Extended) Brief .Psychiatric Rating Scale BPRS domains mean scores were: manic 21.4 ± 8.8, depression and anxiety 20.3 ± 6.2, negative symptoms 13.8 ± 4.6 and positive symptoms 17.7 ± 6.3. BPRS mean score was 77.1± 24.9. The multivariate regression model demonstrated that four variables remain significant and associated with non-adherence; no formal education (OR= 2.11; CI: 0.8 – 3.8) (p=0.04), age (OR= 2.88; CI: 1.2 – 4.4) (p = 0.01), having comorbidity (OR= 3.2; CI: 1.9 – 4.3) (p=0.01) and having concerns about side effects (OR= 2.5; CI: 1.2 – 3.9) (p = 0.03); as they are positively correlated to non-adherence.Conclusion: More than half of participants in this study had low adherence to their antipsychotic agents. Most of patients had strong beliefs in the necessity to use their medications. However, high percentage of the patients had concerns about long-term and potential side effects of antipsychotic medications. Therefore, our role as pharmacist is raising patients’ awareness and beliefs about medications for better treatment outcomes; by educating them about anti-psychotics, their adverse events and conducting several interventions regarding patient compliance.
- ItemAntibiotics Dispensing Patterns in The Community Pharmacies in Gaza Governorate(Al-Quds University, 2008-03-01) Mostafa Omar El-Ghosain; مصطفى عمر حسين
- ItemSynthesis, in vitro and Biophysical Studies of Novel Fluorescent Platinum(IV) Prodrug Derivatives and their Delivery by Fusogenic Liposomes as Nano-carriers into Cancer Cells(Al-Quds University, 2022-08-17) Zeinab Khalid Mohammad Breijyeh; زينب خالد محمد بريجيةIn spite the wide spread of treatment for cancer, patients still suffer from serious side effects. Platinum(II) complexes such as Cisplatin, Oxaliplatin and Carboplatin are used to treat several types of cancer but due to general toxicity and intrinsic/acquired chemo-resistance their therapeutic application is restricted. On the other hand, Platinum(IV) prodrugs with two additional axial ligands, are more stable inert form of Pt(II) compound with less side effects and have the ability to deliver Pt(II) to cancer cell by introducing targeted or lipophilic ligand to the axial position. Few platinum(IV) complexes have advanced to clinical trials, therefore, several mechanisms such as fluorescent imaging and others have been used to understand Pt(IV) mechanism of action intracellularly by the conjugation of lipophilic fluorophore to the axial ligand of platinum compounds. In this project a series of fluorescent labeled platinum(IV) prodrugs were synthesized and characterized. Platinum(IV) complexes was conjugated to high lipophilic fluorescent long chain carboxylate ligandsat the axial hydroxide ligand via a cleavable ester linkage to produce a fluorescent labelled platinum(IV) prodrugs.Fluorescent lipophilic amino acid derivatives and platinum(IV) prodrugs were characterized by melting point, fourier transform infrared spectroscopy, proton and carbon nuclear magnetic resonance spectroscopy, Ultra-performance liquid chromatography, electrospray ionization mass spectrometry (ESI-MS) analytical techniques. Stability study for fluorescent platinum(IV) prodrugs were investigated using Ultra-performance liquid chromatography (UPLC) at constant temperature (37°C) using 7.4 pH bufferto resemble pH of blood. على الرغم من الانتشار الواسع لعلاج السرطان، لا يزال المرضى يعانون من آثار جانبية خطيرة. يتم استخداممركبات الجيل الثانيمن البلاتينمثل سيسبلاتين وأوكساليبلاتين وكاربوبلاتين لعلاج عدة أنواع من السرطان ولكن بسبب السمية العامة والمقاومة الكيميائية الجوهرية/المكتسبة، يتم تقييد تطبيقها العلاجي. من ناحية أخرى، فإن الجيل الرابع من مركبات البلاتين ذات الروابط المحورية الإضافية، هي عبارة عن شكل خامل أكثر استقرارًا من مركبات الجيل الثانيمع آثار جانبية أقل ولديها القدرة على تسليمالشكل الفعال وهو الجيل الثاني إلى الخلايا السرطانية عن طريق ربط مركبات دهنية او مركبات تستهدف الخلايا السرطانية إلى الروابط المحورية. تقدم عدد قليل من المركبات البلاتينيةالجيل الرابع إلى التجارب السريرية، لذلك، يجب استخدام العديد من الآليات مثل التصوير الفلوري وغيرها لفهم آليةعملها داخل الخلية وذلك عن طريق اقتران مركبات مضيئةدهنية إلى الروابط المحورية الجديدة. في هذا المشروع، تم تصنيع سلسلة من طلائعالمركبات البلاتينية المضيئة حيث تم ربط المركبات البلاتينية باحماض أمينيةدهنية مضيئة طويلة. تم تشخيص طلائع الأحماض الأمينية الدهنية المضيئةعن طريق، نقطة الانصهار،التحليل الطيفي للأشعة تحت الحمراء، والرنين المغناطيسي النووي، وكروماتوجرافيا سائلة فائقة الأداء، وتقنياتقياس الطيف الكتلي للتأين بالرش الكهربائيللتأكد من المركبات المصنعة. وتم دراسةهذه الطلائع داخل المختبر باستخدام كروماتوجرافيا سائلة فائقة الأداءعلى درجة حرارة ثابتة(37 درجة مئوية) ودرجة حموضة7.4 مشابهة لدرجة حموضة الدم.