Pharmacy

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Anti-cancer Prodrugs-Three Decades of Design
(2015-07-31) Horani, Waad; Thawabteh, Ameen; Scrano, Laura; A. Bufo, Sabino; Mecca, Gennaro; Karaman, Rafik
The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process.
Antibacterial Predrugs-from 1899 till 2015
(WJPPS,Dr. T Pal, 2015-07-08) Elayyan, Sabrin; Karaman, Donia; Mecca, Gennaro; Scrano, Laura; Bufo, Sabino A.; Karaman, Rafik
The predrug (prodrug) term involves chemically modified inert compound which upon an administration releases the active parent drug to elicit its pharmacological response within the body. For many years, the predrug strategy has been extensively developed to solve many unwanted drug properties. This approach has several advantages over conventional drug administration and it has the potential to be quite effective method for the treatment of diseases in the future. In this mini-review we describe a number of antibacterial agents‘ predrugs, and the ways by which predrug strategy was exploited to overcome many pharmaceutical and pharmacokinetic problems that the parent active antibacterial drugs suffer from such as, low bioavailability by increasing or decreasing lipophilicity, site selectivity for higher absorption and less toxicity, short duration of action to increase patient compliance, rapid metabolism to increase oral bioavailability and masking bitter sensation which is crucial for geriatric and pediatric patient compliance.
Assessment of Patient Safety Culture in the Palestinian Hospital Pharmacies
(AL-Quds University, 2011) وفاء جمال حسن الزغاري; Wafa Jamal Hassan Zaghari; معتصم حمدان; Hussein Hallak; Ali Shaar
Background: Patient safety culture assessment in pharmacies is increasing largely worldwide, many tools that were used to assess patient safety culture at the hospital settings as a whole are now adapted to be used for pharmacies. One of the most commonly used and rigorously validated tools to measure patient safety culture is the Safety Attitudes Questionnaire (SAQ). The tool consists of 30 items that cover six safety culture domains. The intention of this research is to map the patient safety culture in the Palestinian hospital pharmacies, this will be achieved through measuring and analyzing the patient safety culture domains there, understanding factors influencing safety culture and examine variations between different hospital pharmacies. This assessment helps in determining safety culture domains that are considered as areas of strength, and safety culture domains that are considered as areas of weakness for each hospital pharmacy. Mapping patient safety culture in hospital pharmacies will end up by directing each hospital pharmacy to improve areas of weakness effectively and efficiently. Purpose: To assess patient safety culture in the Palestinian hospital pharmacies, and to assess the association of hospitals and respondents characteristics with patient safety culture. Methods: A cross-sectional design was used. The English version of the SAQ was translated and adapted to the Palestinian context. The survey was carried out in (28) Palestinian hospitals in the West Bank and East Jerusalem. All pharmacist assistants, pharmacist, and clinical pharmacists in these hospitals were targeted, estimated to 115 personnel. Items mean and scale scores were calculated. Then a composite score equivalent to the arithmetic mean of the scale scores were also calculated. In order to identify areas of strength and areas for potential improvement, the percentages of positive responses for the survey domains and items were calculated. Univariate analysis was used to test associations between composite patient safety scores and different respondent and hospital characteristics. viii Findings: 73 persons participated in the study, response rate was 68.8%. Females were 66.7%, 51% were pharmacist or clinical pharmacist, and 84.7% were with experience ≥ 5 years in profession. Two SAQ domains, job satisfaction and working conditions, were identified as areas of strength and received ≥75% of positive responses. Patient safety level was graded as “accepted” by (50%) of the respondents and none gave their pharmacy a “Poor” or “Failing” grade. Event reporting was very low, (66%) of the respondents didn’t report any event in the past year. In regard to the associations between safety culture domains scores with participants and hospital characteristics, the association was statistically significant (P<0.05) in regard to hospital ownership with the teamwork climate (P=0.02), perception of management (P=0.03), job satisfaction (P=0.001), and working conditions (P=0.02) and all in favor of the private and NGO hospitals. Participants working in hospitals sized <50 beds were more positive towards perception of management climate than their counterparts in larger sized hospitals (P=0.031). The overall safety score was significantly associated only with the hospital ownership (P=0.002) in favor of the private and NGO hospitals. No statistically significant associations were found between safety culture domains and the participant’s age, gender, years of experience in profession and hospital, level of education, working hours, and job title. The safety culture domain scores varied largely among different hospital pharmacies. None of the six domains were positive for four hospitals, twelve hospitals have negative total safety score and the best result was having five positive safety domains and a positive total safety score and this result was achieved only by two hospitals. Conclusions: Safety culture assessment results revealed areas for potential improvement in Palestinian hospital pharmacies. Hospitals need to formulate specific patient safety culture interventions to address these weaknesses
Computationally Designed Enzyme Models to Replace Natural Enzymes in Prodrug Approaches
(2012-11-16) Karaman, Rafik
The striking efficiency of enzyme catalysis has inspired many organic chemists to explore enzyme mechanisms by studying certain intra molecular processes such as enzyme models which proceed faster than their intermolecular counterparts. This research brings about the important question of whether enzyme models will replace natural enzymes in the conversion of prodrugs to their parental drugs. Enzymes are mandatory for the inter conversion of many prodrugs to their parental drugs. Among the most important enzymes in the bioconversion of prodrugs are amides (ex. trypsin, chymotrypsin, elastase, carboxypeptidase, and aminopeptidase) and ester-based prodrugs (ex. paraoxonase, carboxylesterase, acetylcholinesterase and cholinesterase). Most of these enzymes are hydrolytic enzymes, however, non-hydrolytic enzymes, including all cytochrome P450 enzymes, are also capable of catalyzing the bioconversion of ester and amide-based prodrugs [1].
Cost-utility analysis of a pharmacy-led self-management programme for patients with COPD
(Springer Science+Business Media B.V. 2011, 2011-06-04) Khdour, Maher R.; Agus, Ashley M.; Kidney, Joseph C.; Smyth, Bronagh M.; Elnay, James C.; Crealey, Grainne E.
Objective: To undertake a cost-utility analysis (CUA) of a pharmacy-led self-management programme for Chronic Obstructive Pulmonary Disease (COPD). Setting: A single outpatient COPD clinic at the Mater Hospital, Belfast, Northern Ireland between. Method: CUA alongside a randomised control trial. The economic analysis used data from 127 COPD patients aged over 45 years, with an FEV1 of 30–80% of the predicted normal value. Participants received either a pharmacy-led education and selfmanagement programme, or usual care. One year costs were estimated from the perspective of the National Health Service and Personal Social Services and quality-adjusted life years (QALYs) were calculated based on responses to the EQ-5D at baseline, 6 and 12 months. Main outcome measure: Cost per QALY gained. Results: The mean differences in costs and effects between the self-management and education programme and usual care were -£671.59 (95 CI%: -£1,584.73 to -£68.14) and 0.065 (95% CI; 0.000–0.128). Thus the intervention was the dominant strategy as it was both less costly and more effective than usual care. The probability of the intervention being costeffective was 95% at a threshold of £20,000/QALY gained. Sensitivity analyses indicated that conclusions were robust to variations in most of the key parameters. Conclusion: The self-management and education programme was found to be highly cost-effective compared to usual care. Further research is required to establish what aspects of self-management and education programmes have the greatest impact on cost-effectiveness.
Diclofenac Codrugs and Prodrugs-Three Decades of Design
(‎WJPPS,Dr. T Pal, 2015-06-08) Dweib, khuloud; Jumaa, Salma; Thawabteh, Ameen; Scrano, Laura; Bufo, Sabino A.; Mecca, Gennaro; Karaman, Rafik
Prodrugs or predrugs are inactive molecules which become active after in vivo conversion to release the active parent drug. The prodrug’s cleavage can be catalyzed by metabolic enzymes or can occur by chemical means without the involvement of enzymes. Prodrugs are designed to improve undesirable physicochemical and pharmacokinetic properties of their parent drugs. Non-steroidal anti-inflammatory (NSAIDs) drugs are among the most commonly used drugs for treatment of pain, inflammation and fever. Despite their frequent use, these agents suffer from gastrointestinal side effects that limit their use for those patients with gastrointestinal conditions. This mini review discusses the design, synthesis and pharmacological effects of prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs) Diclofenac sodium or potassium. It argues that the prodrug approach has the potential to eliminate Diclofenac associated gastrointestinal complications, increases its bioavailability and masks its bitter taste.
Extent and nature of unlicensed and off-label medicine use in hospitalized children in Palestine
(Springer, 2011-05-13) Hussein Hallak; Maher khdour; Alayasa, Kawther; AlShahed, Qusai; Hawwa, Ahmed; McElnay, James
Objective of the study To determine the extent and nature of unlicensed/off-label prescribing patterns in hospitalised children in Palestine. Setting Four paediatric wards in two public health system hospitals in Palestine [Caritas children’s hospital (Medical and neonatal intensive care units) and Rafidia general hospital (Medical and surgical units)]. Method A prospective survey of drugs administered to infants and children \18 years old was carried out over a five-week period in the four paediatric wards. Main outcome measure Drug-licensing status of all prescriptions was determined according to the Palestinian Registered Product List and the Physician’s Desk Reference. Results Overall, 917 drug prescriptions were administered to 387children. Of all drug prescriptions, 528 (57.5%) were licensed for use in children; 65 (7.1%) were unlicensed; and 324 (35.3%) were used off-label. Of all children, 49.6% received off-label prescriptions, 10.1% received unlicensed medications and 8.2% received both. Seventy-two percent of off-label drugs and 66% of unlicensed drugs were prescribed for children \2 years. Multivariate analysis showed that patients who were admitted to the neonatal intensive care unit and infants aged 0–1 years were most likely to receive a greater number of off-label or unlicensed medications (OR 1.80; 95% CI 1.03–3.59 and OR 1.99; 95% CI 0.88–3.73, respectively). Conclusion The present findings confirmed the elevated prevalence of unlicensed and off-label paediatric drugs use in Palestine and strongly support the need to perform well designed clinical studies in children.
Impact of pharmaceutical care on health outcomes in patients with COPD
(Springer Science+Business Media B.V. 2011, 2011-11-20) Khdour, Maher; Jarab, Anan; AlQudah, Salam; Shamssain, Mohammed; Mukattash, Tareq
Background Chronic obstructive pulmonary disease (COPD) treatment goals are often not achieved despite the availability of many effective treatments. Furthermore, clinical pharmacist interventions to improve clinical and humanistic outcomes in COPD patients have not yet been explored and few randomized controlled trials have been reported to evaluate the impact of pharmaceutical care on health outcomes in patients with COPD. Objective The aimof the present studywas to evaluate the impact of pharmaceutical care intervention,with a strong focus on self-management, on a range of clinical and humanistic outcomes in patients with COPD. Setting Outpatient COPD Clinic at the Royal Medical Services Hospital. Method In a randomised, controlled, prospective clinical trial, a total of 133 COPD patients were randomly assigned to intervention or control group. A structured education about COPD and management of its symptoms was delivered by the clinical pharmacist for patients in the intervention group. Patientswere followed up at 6 months during a scheduled visit. Effectiveness of the intervention was assessed in terms of improvement in health-related quality of life,medication adherence, disease knowledge and healthcare utilization. Data collected at baseline and at the 6 month assessment was coded and entered into SPSS software version 17 for statistical analysis. A P value of\0.05 was considered statistically significant. Main outcome measure The primary outcome measure was health-related quality of life improvement. All other data collected including healthcare utilization, COPD knowledge and medication adherence formed secondary outcome measures. Results A total of 66 patients were randomized to the intervention group and 67 patients were randomized to the control group. Although the current study failed to illustrate significant improvement in health-related quality of life parameters, the results indicated significant improvements in COPD knowledge (P\0.001), medication adherence (P\0.05), medication beliefs (P\ 0.01) and significant reduction in hospital admission rates (P\0.05) in intervention patients when compared with control group patients at the end of the study. Conclusion The enhanced patient outcomes as a result of the pharmaceutical care programme in the present study demonstrate the value of an enhanced clinical pharmacy service in achieving the desired health outcomes for patients with COPD.
Mefenamic acid Prodrugs and Codrugs- Two Decades of Development
(2015-06-05) Abu-Jaish, Alaa; Mecca, Gennaro; Jumaa, Salma; Thawabteh, Ameen; Karaman, Rafik
prodrugs are bioreversible derivatives of drug molecules that undergo intermolecular or intramolecular reactions by enzymatic or chemical biotransformation in the human body to give the corresponding active parent drugs and a non-toxic promoiety. Prodrugs have been extensively and successfully used as a chemical tool for modification of the physicochemical, pharmacokinetic as well as pharmacodynamic characteristics of commonly used drugs and new drugs.This mini review focuses on the design, synthesis and pharmacological effects of several prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs), mefenamic acid. Exploitation of the prodrug approach has the potential to achieve a reduction of mefenamic acid GI (gastrointestinal) intolerance, enhance its bioavailability, mask its unpleasant sensation and prolong its duration of action. In addition, utilizing the prodrug concept migh enhance the bioavailability of the counter partner drug of mefenamic acid codrug by increasing its lipophilicity.
A Novel Mathematical Equation For Calculating The Number of ATP Molecules Generated From Sugars In Cells
(WJPR,Tara Pal,WJPR, 2015-05-23) Karaman, Rafik; Khawaja, Yahya
Adenosine triphosphate (ATP) is critical for all life from the simplest to the most complex. All organisms from the microscopic to humans utilize ATP as the source for their primary energy currency. This manuscript describes a novel method to calculate the number of ATP molecules generated from the consumption of any sugar (having 3-7 carbons). This calculation method based on the oxidation states of the sugar’s carbons. The time needed to calculate the number of ATP molecules by this method is less than 2 minutes whereas that required by the current (regular) method is many hours and even days in some cases. In addition, the current method requires drawing all biochemical processes that the sugar undergoes upon its cellular respiration (oxidation) while our method described herein does not.
Paracetamol biodegradation by activated sludge and photo-catalysis and its removal by a micelleclay complex, activated charcoal and reverse osmosis membranes
(Taylor & Francis, 2016-03-07) Karaman, Rafik; Khamis, Mustafa; Abbadi, Jehad; Amro, Ahmad; Qurie, Mohannad; Ayyad, Ibrahim; Ayyash, Fatima; Hamarsheh, Omar; Yaqmour, Reem
Kinetic studies on the stability of the pain killer paracetamol in Al-Quds activated sludge demonstrated that paracetamol underwent biodegradation within less than one month to furnish p-aminophenol in high yields. Characterizations of bacteria contained in Al-Quds sludge were accomplished. It was found that Pseudomonas aeruginosa is the bacterium most responsible for the biodegradation of paracetamol to p-aminophenol and hydroquinone. Batch adsorptions of paracetamol and its biodegradation product (p-aminophenol) by activated charcoal and a composite micelle (octadecyltrimethylammonium)-clay (montmorillonite) were determined at 25°C. Adsorption was adequately described by a Langmuir isotherm, and indicated better efficiency of removal by the micelle-clay complex. The ability of bench top reverse osmosis (RO) plant as well as advanced membrane pilot plant to remove paracetamol was also studied at different water matrixes to test the effect of organic matter composition. The results showed that at least 90% rejection was obtained by both plants. In addition, removal of paracetamol from RO brine was investigated by using photocatalytic processes; optimal conditions were found to be acidic or basic pH, in which paracetamol degraded in less than 5 min. Toxicity studies indicated that the effluent and brine were not toxic except for using extra low energy membrane which displayed a half maximal inhibitory concentration (IC-50) value of 80%.
Pharmacists’ Knowledge, Attitudes and Practices Towards Herbal Remedies In West Bank, Palestine
(International Medical Society, 2016-06-03) Khdour, Maher R.; Kurdi, Manar; Hallak, Hussein O.; Jarab, Anan S.; Dweib, Mohammad; Al-Shahed, Qusai N.
Background: There is an increasing trend towards consumption of complementary and alternative herbal products in many parts of the world. Objectives: The purpose of this study was to investigate the knowled - ge and attitudes among pharmacists in West Bank, Palestine towards the use of herbs. Methods: Self-administered questionnaire was designed as the study instrument and distributed among 350 qualified pharmacists working in government and private pharmacies in West Bank, Palestine. Results: The response rate was 82.9% (290/350). The mean age of the pharmacists was 32.9 (SD=6.5) years. The majority of the phar - macist 238 (82.1%) worked in the community pharmacies and their experience in practice ranged from 1 to 26 years. Product package instructions and product representative were the most consulted by the pharmacists (128; 44.2% and 73; 25.2% respectively). General health tonic preparations were the most widely dispensed drugs (142; 48.9%), followed by cough preparations (55; 19.0%) and slimming agents (64; 22.1%). The Majority of pharmacists (195; 67.2%) belie - ved herbal remedies were effective; however, about fifty percent of the pharmacists had concern about their safety. The knowledge of respondents about the indications of herbal medicine was good, but their awareness of interactions, contraindications and adverse effects was inadequate. The majority of Pharmacists (255; 87.9%) believed that herbal product should undergo increased regulation and (215; 74.9%) believed that information available about herbal and natural product isn't adequate.
Pharmacovigilance and Adverse Drug Reactions Reporting Process in West-Bank, Palestine
(Deanship of Scientific Research at An Najah National University, 2016-10-09) Khdour, Maher; Yaghmour, Nima; Hallak, Hussein; Dweib, Mohammad; Al-Shahed, Qusai; Jarab, Anan
Active national pharmacovigilance programmes are needed to monitor adverse drug reaction (ADR) data in local populations. The objective of this study was to describe the knowledge, experiences, attitudes and perceived barriers to reporting of suspected ADRs by community and hospital pharmacists in West Bank, Palestine. Between December 2014 and March 2015 we conducted a survey about the knowledge and attitude of pharmacists (n = 270) using a face-to-face questionnaire. The questionnaire consisted of questions about the sociodemographic characteristics of the pharmacists, their knowledge of pharmacovigilance and their attitudes towards ADR reporting. Main outcomes measured: The majority of the pharmacists (62.6%) worked in the community pharmacies and more females responded to the questionnaire than males (59% vs 41%). only 11.9% could conceptually or actually define ‘pharmacovigilance’ correctly while one quarter of the respondent pharmacist (24.9%) could define ADR correctly. The hospital clinical pharmacists defined ‘pharmacovigilance’ correctly with higher significance (P<0.001) when compared with community pharmacists. Only 12.2% had ever reported an ADR. The majority of these reports (85%) done by the hospital pharmacists (p<0.0001). The main reasons that discourage the pharmacists from reporting ADRs were ‘‘no enough information available from the patient (76.7%)’’, and ‘‘they did not know how to report (66.7%)’’. The majority of the respondents (92.0%) felt that reporting ADR was their duty and (82%) participants were interested in participating in the National Pharmacovigilance Programme in Palestine. The results show that Palestinian pharmacists have poor knowledge about pharmacovigilance. There is an urgent need for educational programs to train them about pharmacovigilance and ADR reporting scheme.
Prodrugs targeting the central nervous system (cns)
(2015-08-07) Salameh, Falasteen; Karaman, Donia; Karaman, Rafik
The classical approach for delivery of drugs into the central nervous system (CNS) is associated with adverse effects and it has many limitations. Therefore, extensive efforts have been done in searching and developing novel methods for achieving such delivery. This minireview discusses the design and synthesis of selected targeting prodrugs for the treatment of conditions related to impairment in the CNS such as Parkinson‘s and Alzheimer‘s diseases. Such approaches include targeting prodrugs which are designed to interact with unique cellular conditions at the target site, especially the availability of certain enzymes and transporters at these sites. In addition, part of this mini-review is devoted to prodrugs design based on enzyme models that have been invoked to understand how enzymes catalyzebiotransformation. In this approach, the prodrugs design isdone using quantum molecular orbital and molecular mechanics methods. The equations obtained from correlations of experimental and calculated rate values for some intramolecular processes are used to predict parameters for other intramolecular processes that can be utilized as prodrugs linkers. In this approach, there is no need for enzymes to catalyze the conversion of the prodrug to its active parent drug and the conversion rate of the prodrug is dependent only on those factors playing dominant role in the rate-limiting step of the process.
Societal perspectives on community pharmacy services in West Bank - Palestine
(2012-03-12) Khdour, Maher R.; Hallak, Hussein O.
Understanding the public's view of professional competency is extremely important; however little has been reported on the public’s perception of community pharmacists in Palestine Objectives: To determine the perception of Palestinian consumers of the community pharmacist and the services they offer Method: This project used the survey methodology administered by structured interviews to consumers who attended the 39 randomly selected pharmacies, in six main cities in Palestine. The questionnaire had range of structured questions covering: Consumers’ patronage patterns, consumers’ interaction with community pharmacists, consumers’ views on how the pharmacist dealt with personal health issues, procedure with regard to handling private consultations. Results: Of 1,017 consumers approached, 790 consumers completed the questionnaire (77.7 %). Proximity to home and presence of knowledgeable pharmacist were the main reasons for patients to visit the same pharmacy. Physicians were identified as the preferred source of advice by 57.2% and pharmacists by 23.8%. Only 17% of respondents considered pharmacists as health professionals who know a lot about drugs and are concerned about and committed to caring for the public. In addition, 49% indicated that pharmacists spoke more quietly cross the counter during counseling and almost one third reported that the pharmacist used a private area within the pharmacy. The majority of respondents would be happy to receive different extended services in the community pharmacy like blood pressure monitoring. Conclusions: Palestinian consumers have a positive overall perception of community pharmacists and the services they offer. Awareness should be created amongst the public about the role of pharmacist and the added value they can provide as health care professional. There is a need to consider privacy when giving patient counseling to increase user satisfaction.

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