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Six aminoethyl and aminobutyl esters of ketorolac containing 1-methylpiperazine (MPE and MPB), N-acetylpiperazine (APE and APB) or morpholine (ME and MB), were synthesized and their hydrolysis kinetics were studied. The hydrolysis was studied at pH 1 to 9 (for MPE, APE and ME) and pH 1 to 8 (for MPB, APB and MB) in aqueous phosphate buffer (0.16 M) with ionic strength (0.5 M) at 37°C. Calculation of k(obs), construction of the pH-rate profiles and determination of the rate equations were performed using KaleidaGraph® 4.1. The hydrolysis displays pseudo-first order kinetics and the pH-rate profiles shows that the aminobutyl esters, MPE, APB and MB, are the most stable. The hydrolysis of the ethyl esters MPE, APE and ME, depending on the pH, is either fast and catalyzed by the hydroxide anion or slow and uncatalyzed for the diprotonated, monoprotonated and nonprotonated forms. The hydrolysis of the butyl esters showed a similar profile, albeit it was also catalyzed by hydronium cation. In addition, the hydroxide anion is 105 more effective in catalyzing the hydrolysis than the hydronium cation. The hydrolysis pattern of the aminoethyl esters is affected by the number and pKa of its basic nitrogen atoms. The monobasic APE and ME, show a similar hydrolysis pattern that is different than the dibasic MPE. The length of the side chain and the pKa of the basic nitrogen atoms in the aminoethyl moiety affect the mechanism of hydrolysis as the extent of protonation at a given pH is directly related to the pKa.
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Anti-Inflamatórios não Esteroides/química , Inibidores de Ciclo-Oxigenase/química , Ésteres/química , Cetorolaco/análogos & derivados , Pró-Fármacos/química , Anti-Inflamatórios não Esteroides/síntese química , Catálise , Inibidores de Ciclo-Oxigenase/síntese química , Estabilidade de Medicamentos , Ésteres/síntese química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Hidrólise , Hidróxidos/química , Cetorolaco/química , Cinética , Modelos Moleculares , Estrutura Molecular , Morfolinas/química , Oniocompostos/química , Piperazinas/química , Pró-Fármacos/síntese química , PrótonsRESUMO
There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug-polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10 min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation.
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Resinas Acrílicas/química , Domperidona/química , Antagonistas de Dopamina/química , Excipientes/química , Administração Oral , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Domperidona/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Composição de Medicamentos , Dureza , Concentração de Íons de Hidrogênio , Povidona/química , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos , Termogravimetria , Fatores de TempoRESUMO
The design and the synthesis of prodrugs for nonsteroidal anti-inflammatory drugs (NSAIDs) have been given much attention by medicinal chemists, especially in the last decade. As a therapeutic group, NSAIDs are among the most widely used prescribed and over the counter (OTC) medications. The rich literature about potential NSAID prodrugs clearly shows a shift from alkyl, aryalkyl or aryl esters with the sole role of masking the carboxylic acid group, to more elaborate conjugates that contain carefully chosen groups to serve specific purposes, such as enhancement of water solubility and dissolution, nitric oxide release, hydrogen sulfide release, antioxidant activity, anticholinergic and acetylcholinesterase inhibitory (AChEI) activity and site-specific targeting and delivery. This review will focus on NSAID prodrugs that have been designed or were, later, found to possess intrinsic pharmacological activity as an intact chemical entity. Such intrinsic activity might augment the anti-inflammatory activity of the NSAID, reduce its side effects or transform the potential therapeutic use from classical anti-inflammatory action to something else. Reports discussed in this review will be those of NO-NSAIDs, anticholinergic and AChEI-NSAIDs, Phospho-NSAIDs and some miscellaneous agents. In most cases, this review will cover literature dealing with these NSAID prodrugs from the year 2006 and later. Older literature will be used when necessary, e.g., to explain the chemical and biological mechanisms of action.
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Anti-Inflamatórios não Esteroides , Antagonistas Colinérgicos , Medicamentos sem Prescrição , Pró-Fármacos , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacocinética , Antagonistas Colinérgicos/uso terapêutico , Humanos , Medicamentos sem Prescrição/química , Medicamentos sem Prescrição/farmacocinética , Medicamentos sem Prescrição/uso terapêutico , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/uso terapêuticoRESUMO
PURPOSE: This wisdom of experience commentary, from peer academic reviewers serving on accreditation teams, will discuss benefits and challenges of international and national virtual accreditation visits (VAVs) using a "What? So What? Now What?" reflective model. DESCRIPTION: Onsite accreditation reviews for health professional education programs require investments in time, effort, and money to maintain program alignment with accreditation standards and continuously generate quality practitioners. When COVID-19 entered the accreditation world, reviewers had to pivot modalities to a VAV format. ANALYSIS/INTERPRETATION: Adaptation and expectations of VAVs present several challenges. Barriers and advantages will be discussed as well as implications for the future. While medical and pharmacy education standardization has long been established, the authors propose national and international accrediting bodies will utilize the ingenuity of emergency COVID-19-driven onsite accreditation alternatives to develop protocols for novel accreditation methodology. CONCLUSIONS: Whether the continued mutation of COVID-19 prevents the return to previous accreditation visits or not, the experiences gained from the emergency-driven VAV, can inform and enrich accrediting bodies knowledge, theories, and practices of future VAVs. IMPLICATIONS: Higher-education institutions, accreditation bodies, and government entities will use experiences during COVID-19 to transform and improve academic requirements and future practices. Even if there is a full return to onsite reviews, such guidelines or improved versions of them can be applied to situations where immobility or restricted mobility is an issue, such as in illness, pregnancy, travel, war, etc. It is crucial for educators and accrediting bodies to evolve as we navigate these unprecedented times.
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COVID-19 , Farmácias , Farmácia , Acreditação/métodos , Humanos , PandemiasRESUMO
Nicotinic acid is therapeutically the optimum antihyperlipidemic agent, yet its intolerable cutaneous flushing hinders its wide clinical implication. The codrug of nicotinic acid and ibuprofen (IBP) was synthesized in the aim of overcoming the troublesome side effect of nicotinic acid by blockade of prostaglandin synthesis through released IBP, thus enhance patient's compliance. The physico-chemical properties of codrug namely solubility, partition coefficient, and pKa were determined. Its solubility in aqueous and organic solvents was highest in 0.1 M HCl and isopropanol, respectively. The kinetics of hydrolysis of the codrug and IBP 2-hydroxyethyl ester was studied in aqueous phosphate buffer solution in pH 1.2, 6.8, and 7.4 at 70°C, 80°C, and 90°C. The hydrolysis was found to be pH dependent and followed Arrhenius equation. The half-life of codrug and IBP 2-hydroxyethyl ester at 25°C in pH 7.4 was 218 days and 3 years, respectively. In vitro enzymatic hydrolysis of codrug and IBP 2-hydroxyethyl ester was studied in human plasma and rat liver homogenate. Codrug and IBP 2-hydroxyethyl ester exhibited faster in vitro enzymatic hydrolysis than in vitro chemical hydrolysis. The pseudo-first-order rate constants were 0.0113, 0.177 min(-1) for codrug and 0.0006, 0.0569 min(-1) for IBP 2-hydroxyethyl ester in human plasma and rat liver homogenate, respectively. Thus, nicotinic acid will be rapidly released from codrug to manage dyslipidemia, followed by the later release of IBP from IBP 2-hydroxyethyl ester to alleviate nicotinic acid cutaneous flushing.
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Inibidores de Ciclo-Oxigenase/síntese química , Hipolipemiantes/síntese química , Ibuprofeno/síntese química , Niacina/síntese química , Animais , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Combinação de Medicamentos , Desenho de Fármacos , Dislipidemias/tratamento farmacológico , Meia-Vida , Humanos , Hidrólise , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Ibuprofeno/química , Ibuprofeno/farmacologia , Masculino , Niacina/química , Niacina/farmacologia , Ratos , Ratos WistarRESUMO
INTRODUCTION: The COVID-19 pandemic imposed dramatic changes on educational practices worldwide. Many universities and schools have moved into the delivery of their courses and educational programs utilizing fully electronic online modes. This study aims to evaluate the pharmacy student distance online learning experience during the COVID-19 pandemic. METHODS: A cross-sectional survey was utilized where a 3-domain survey questionnaire focused on preparedness, attitude and barriers was distributed to students at the time of conclusion of the semester. Each domain consists of multiple questions that made up a score that reflects their preparedness, attitude as well as barriers relevant to distance online learning experience. The survey was voluntarily, and all data were collected and recorded via google forms with maintaining anonymity. RESULTS: The response rate was about 75% (n = 309). The results' analysis revealed no gender differences in any of these domains. However, there were some variable responses among different educational levels. The average preparedness score was 32.8 ± 7.2 (Max 45), the average attitude score was 66.8 ± 16.6 (Max 105), and the average barrier score was 43.6 ± 12.0 (Max 75). There was statistical significance difference in both preparedness score and attitude scores between different professional years (P-value <.05). However, there was no difference in barrier scores among all professional years. The results indicated that about 61.4% of the students agreed on that college of pharmacy was well-prepared and ready for the online education during the emerging COVID-19 pandemic with complete transition into online education. The results also indicated that 49.2% of the students showed positive attitude toward the provided online learning. The results indicated that about 34% of the students identify some barriers toward the provided online learning. Finally, there were strong association between the need for training on how to receive online courses and preparedness and barriers scores. DISCUSSION AND CONCLUSION: E-learning experience pose challenges and presents opportunities during emergency situations. The need for training for students and faculty was highly associated with the preparedness and barriers domains rather than the infrastructure or computer literacy, so the school can improve their experience by addressing these needs.
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Objective. To establish an academic curricular collaboration between the newly established college of pharmacy at King Saud Bin Abdulaziz Saudi University for Health Sciences (KSAU-HS) and a US college of pharmacy accredited by the Accreditation Council for Pharmacy Education, and assess measures of success. Methods. Criteria for selecting a college for collaboration were established. A systematic approach was followed in negotiating legal, logistical, and financial issues with the selected collaborating institution. Course materials were transferred and implemented and minimal changes were made to the alignment and sequencing of lectures. The faculty at KSAU-HS developed and implemented research and seminar courses. Pharmacy practice experiences were designed and rubrics were developed. Results. All courses were implemented successfully. The PharmD students scored significantly higher in all academic levels in a benchmarked progress test than did students in other programs. Students' evaluation of 43 first-, second-, and third-year courses in 2017-2018 using a survey that assessed numerous aspects of each course showed significantly higher overall satisfaction than the institutional averages. Also, female students indicated significantly higher satisfaction with the PharmD program than did male students. Conclusion. The transfer and implementation of an accredited PharmD curriculum to the KSAU-HS College of Pharmacy went smoothly and the program was launched on time. Learning and teaching success was facilitated by the KSAU-HS faculty. Program outcomes were verified by students' high scores on a benchmarked examination and by their satisfaction with the courses.
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Currículo , Educação em Farmácia/organização & administração , Docentes de Farmácia/organização & administração , Estudantes de Farmácia/psicologia , Acreditação , Avaliação Educacional , Feminino , Humanos , Cooperação Internacional , Masculino , Arábia Saudita , Inquéritos e Questionários , Estados UnidosRESUMO
The methanolic extract of the whole plant of Echium glomeratum Poir. (Boraginaceae) has afforded five pyrrolizidine alkaloids, three that were (7S, 8R)-petranine (1), (7S, 8S)-petranine (2), and (7R, 8R)-petranine (3a) or (7R, 8S)-petranine (3b), comprising a tricyclic pyrrolizidine alkaloids subclass; and two that were known but to the species: 7-angeloylretronecine (4) and 9-angeloylretronecine (5). All compounds were tested against a human tumor panel for cytotoxicity; no activity was observed (EC50 values>20microg/ml).
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Echium/química , Alcaloides de Pirrolizidina/química , Alcaloides de Pirrolizidina/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Modelos Moleculares , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
The use of immunosuppressants to reduce the likelihood of acute graft rejections is a cornerstone in the post-transplantation management of recipients. However, these agents were always associated with increased risk of deleterious effects such as infections vulnerability and comorbidities. The objective of this review is to discuss the impact of different immunosuppression strategies used in liver transplant recipients (LTRs) on the recurrence of hepatitis C virus (HCV) infections after transplantation. Traditionally, corticosteroids were a mainstay in immunosuppressive regimens in LTRs. Several trials have suggested early tapering of corticosteroids or steroid-free immunosuppression protocols to minimize metabolic complications and other accompanied adverse events. However, there is no consistent agreement on the apparent benefit of steroid-avoidance regimens on HCV recurrence. At present, calcineurin inhibitors alone or in combination with other immunosuppressants are the standard regimen for immunosuppression in LTRs. Although the use of mycophenolate mofetil and sirolimus were sometimes associated with a significantly lower risk of liver injury as a result of HCV recurrence, they were associated with an increased risk of acute graft rejection compared to calcineurin inhibitors. Consequently, reducing the incidence of HCV recurrence in LTRs could be at the expense of other potential complications. The appropriate selection of adequate immunosuppression could diminish the associated increased risk of HCV recurrence after liver transplantation. However, further clinical studies are still pivotal to establish the appropriate/optimal immunosuppressive therapies for HCV-positive LTRs.
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Objective. To assess pharmacy educators' knowledge of medication safety and their perception toward its integration into the PharmD curriculum in Saudi Arabia. Methods. A survey was administered to pharmacy educators at a college of pharmacy and its affiliate hospital. Knowledge, training, and perception toward integrating medication safety into the PharmD curriculum were evaluated. Results. More than 50% of respondents indicated that medication safety should be covered within selected courses, and 65% indicated that such courses should be mandatory. Pharmacy practice educators had significantly higher levels of knowledge about medication safety than their nonpractice counterparts. Perceptions toward medication safety integration into the curriculum varied significantly by general discipline, academic degree, years of experience, and gender. Conclusion. Pharmacy educators in Saudi Arabia understand the importance of medication safety and its integration into the curriculum. Further studies are needed to guide curricular change to achieve this integration.
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Atitude do Pessoal de Saúde , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Educação de Pós-Graduação em Farmácia/métodos , Docentes de Farmácia , Conhecimentos, Atitudes e Prática em Saúde , Percepção , Currículo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Feminino , Humanos , Masculino , Arábia Saudita , Faculdades de Farmácia , Estudantes de Farmácia , Inquéritos e QuestionáriosRESUMO
BACKGROUND/AIMS: Liver transplantation (LT) is a life-saving intervention for patients with liver failure. LT recipients' adherence to their therapeutic regimen is an essential element for graft survival. According to WHO, the impact of medication non-adherence in solid organ transplantation has shown to cost $15-100 million annually. The aim of the present study was to identify the factors that best predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in liver transplant recipients. PATIENTS AND METHODS: Adult liver transplant patients at King Abdulaziz Medical City were included in the study. Patients completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) in addition to several socio-demographic and transplant-related data. RESULTS: A total of 154 patients were included in the study and of these 59.7% were adherent. Older age was a significant predictor of adherence (P < 0.05). The mean treatment satisfaction score was 91.9 ± 12.7 in Effectiveness, 80.0 ± 25.9 in Side Effects, 83.5 ± 15.7 in Convenience, and 94.6 ± 8.6 in Global Satisfaction. Further analysis indicated that patients in the adherent group had reported significantly higher satisfaction scores than those in the non-adherent group (P < 0.05) in all treatment satisfaction domains: Effectiveness (94.4 ± 10.4 vs. 88.6 ± 14.8), Side Effects (83.9 ± 22.0 vs. 74.2 ± 30.1), Convenience (87.0 ± 13.9 vs. 77.2 ± 16.1), and Global Satisfaction (96.9 ± 6.6 vs. 91.2 ± 8.6). CONCLUSION: Older patients and those who were more satisfied with their treatment tend to have better adherence to the prescribed medications. Therefore, increasing patients' satisfaction with their treatment should be an integral element of future care plans designed to improve treatment outcomes in liver transplant recipients.
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Transplante de Fígado , Adesão à Medicação , Satisfação do Paciente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND Evidence suggests that patients who are more satisfied with their treatment show better adherence with the prescribed therapy. Although there is valuable data about medication adherence among renal transplant recipients (RTRs), there is a limited literature about their treatment satisfaction and its relation to adherence. The aim of the present study was to investigate factors that can predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in renal transplant recipients. MATERIAL AND METHODS Adult RTRs were included in the study using convenient sampling. The participants were asked to complete the 8-item Morisky Medication Adherence Scale (MMAS-8) and Treatment Satisfaction Scale TSQM 1.4 in addition to several socio-demographic and treatment-related data. The results were statistically analyzed using univariate and multivariate logistic regression modelling in a stepwise procedure. RESULTS A total of 151 RTRs were included in the study, of which 52 were classified as adherent (34%). Univariate analysis showed that, in comparison with non-adherent RTRs, the adherent group demonstrated significantly higher satisfaction scores in the domains of convenience (96.6±8.7 vs. 85.3±19.3), side effects (95.9±14.1 vs. 82.6±24.1), and global satisfaction (93.4±9.8 vs. 86.7±16.7), while they had marginally higher satisfaction scores in the effectiveness domain (90.4±11.6 vs. 86.5±14.5). Results from multiple logistic regression showed that higher likelihood of adherence was significantly associated with increased satisfaction score in the convenience domain [AOR=1.76, 95% CI=(1.21, 2.55); p=0.003] and marginally related to increased satisfaction scores in the side effects domain [AOR=1.31, 95% CI=(0.99, 1.74); p=0.061]. Male RTRs were significantly more likely to be adherent than female RTRs [AOR=2.23, 95% CI=(1.02, 4.84); p=0.043]. CONCLUSIONS Although the adherence rate among RTRs is relatively low, males and RTRs who reported higher treatment satisfaction (convenience and side effects domains) showed better medication adherence. It is recommended that interventional programs for the improvement of dialysis patient adherence should be developed, in addition to designing strategies to improve treatment convenience and knowledge of medication side effects.
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Transplante de Rim/psicologia , Adesão à Medicação/psicologia , Satisfação do Paciente , Transplantados/psicologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Inquéritos e Questionários , Transplantados/estatística & dados numéricosRESUMO
The flexibility of activated factor X (fXa) binding site was assessed employing ligand-based pharmacophor modeling combined with genetic algorithm (GA)-based QSAR modeling. Four training subsets of wide structural diversity were selected from a total of 199 direct fXa inhibitors and were employed to generate different fXa pharmacophoric hypotheses using CATALYST software over two subsequent stages. In the first stage, high quality binding models (hypotheses) were identified. However, in the second stage, these models were refined by applying variable feature weight analysis to assess the relative significance of their features in the ligand-target affinity. The binding models were validated according to their coverage (capacity as a three-dimensional (3D) database search queries) and predictive potential as three-dimensional quantitative structure-activity relationship (3D-QSAR) models. Subsequently, GA and multiple linear regression (MLR) analysis were employed to construct different QSAR models from high quality pharmacophores and explore the statistical significance of combination models in explaining bioactivity variations across 199 fXa inhibitors. Three orthogonal pharmacophoric models emerged in the optimal QSAR equation suggesting they represent three binding modes accessible to ligands in the binding pocket within fXa.
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Fator Xa/química , Relação Quantitativa Estrutura-Atividade , Algoritmos , Sítios de Ligação , Humanos , Ligantes , Modelos Moleculares , Maleabilidade , Ligação ProteicaRESUMO
OBJECTIVES: The shortage of clinical pharmacists in Saudi Arabia has limited the full implementation of pharmaceutical care in most of its hospitals. The National Guard Health Affairs hospitals. This work discussed the Department of Pharmaceutical Care, and the King Saud Bin Abdulaziz University for Health Sciences College of Pharmacy four initiatives that were planned in 2009-2010 to develop and recruit clinical pharmacists, practitioners, or faculty. METHODS: The combined initiatives were aimed at (1) instituting a 4-year clinical skills development career ladder, (2) expanding the National Guard Health Affairs postgraduate residency program, (3) offering scholarships to qualified pharmacy graduates to pursue the PharmD degree and a PGY-1 residency training in the United States, and (4) recruiting non-Saudi clinical pharmacists educated and trained in the United States to ameliorate the current shortage of practitioner. RESULTS: The current number of clinical pharmacists practicing at the National Guard Health Affairs at central region is 24, most of whom are Board Certified by the American Pharmacists Association Board of Pharmacy Specialties. CONCLUSIONS: The four initiatives, based on current trends, suggest that 60-65 positions will be added by 2017-2018, barring attrition. Saudi Arabia and many developing countries will continue to experience a shortage in clinical pharmacists due to the high demand for clinical pharmacy services. A multifaceted approach is recommended to address the problem.
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INTRODUCTION: Bacterial urinary tract infections (UTIs) are very common complications in renal transplant recipients (RTRs). METHODOLOGY: This study is a follow-up to a previous investigation of post-renal transplant UTIs, which led to changes in the antibacterial agents used for prophylaxis and its duration. In this retrospective study of the medical records of 86 RTRs, the incidence, risk factors, causative bacteria, and duration prophylaxis were investigated. RESULTS: The average age of the RTRs was 41.55 ± 14.06 years, and two-thirds of them were males. A total of 57.3% of the RTRs received cadaveric kidneys; the rest received kidneys from living related donors. The prescribed regimen (one month or three months of co-trimoxazole and norfloxacin) was completed by 75% of the RTRs. The incidence of UTIs in the RTRs who received this prophylaxis was 32.3%, which was significantly lower than the incidence with norfloxacin alone (56%). Female gender was found to be a risk factor for post-renal transplant UTIs. Escherichia coli was the most common pathogen (51.7%), followed by Klebsiella and Enterobacter (17.2% each). Most UTIs (86.2%) were detected within the first post-transplant month. CONCLUSIONS: There was no clear advantage to prescribing antibacterial prophylaxis for three months versus one month, as 86.2% of the UTIs occurred within the first month post-transplant regardless of prophylaxis duration. Using co-trimoxazole/norfloxacin compared to norfloxacin alone did positively affect patient outcome by reducing the incidence of UTIs. This study recommends antimicrobial sensitivity-guided modification of the antibacterial agents used for prophylaxis rather than extension of its duration.
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Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Transplante de Rim , Transplantados , Adolescente , Adulto , Idoso , Bactérias/classificação , Infecções Bacterianas/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The dipeptidyl peptidase-IV (DPP-IV) enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels. METHODS: In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point. RESULTS: Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 µM concentration. CONCLUSION: The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.
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Inibidores da Dipeptidil Peptidase IV/síntese química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Desenho de Fármacos , Simulação de Acoplamento MolecularRESUMO
Twenty six α-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar = 2-pyrimidyl) and CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4-0.9 µM, against Staphylococcus aureus than CIPRO, while only compound CD-10 exhibited better activity, 0.1 µM, against Bacillus subtilis than CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (α-phenyl, Ar = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (α-phenyl, Ar = 3-chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 µM against this strain. The NOR derivatives showed lower activity than NOR itself against Staphylococcus aureus, although ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 µM. Two NOR derivatives, ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (α-phenyl, Ar = 3-chlorophenyl) and ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 µM against the same strain. QSAR revealed that while polarity is the major contributing factor in the potency against Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against Bacillus subtilis, with a lesser and variable effect for lipophilicity.
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Medication adherence was assessed in 89 patients on hemodialysis (HD) at the King Abdul Aziz Medical City using an Arabic version of the Morisky Medication Adherence Scale (MASS-8). The results of the study revealed that 31.46% and 40.45% of the participants showed low and medium adherence, respectively, while 28.09% showed high medication adherence. Accordingly, 71.91% of the patients visiting the dialysis unit were considered medication non-adherent. While being of older age (P = 0.012), being married (P = 0.012) increased the level of adherence, being of medium level of education (P = 0.024) decreased adherence levels. On the other hand, gender, presence of a care-giver, number of members in the household and employment status seems to have no effect on the level of medication adherence. These results call upon the practitioners in HD units to develop intervention programs that can increase the level of medication adherence.