Economic evaluation of clinical pharmacy service using integrated health system in tertiary care hospital.

BACKGROUND: Clinical pharmacy services are the specialized practices of pharmacists to provide pharmaceutical care. All these activities are documented as pharmacist interventions to avoid medication errors which occur during prescribing, dispensing, and administration. The purpose of this study is to conduct an economic analysis of the pharmacist interventions using integrated health system. RESEARCH DESIGN AND METHODS: A retrospective study was conducted in a tertiary care hospital. Pharmacist interventions were analyzed by an independent pharmacist. Cost-saving and cost avoidance analyses were carried out for drug-related interventions. Economic analysis was performed and tabulated both in PKR and USD. RESULTS: Out of 1330 interventions, 1250 (95%) interventions were accepted and changed the prescription upon the physician-pharmacist consultation while 71 (5%) were not accepted. Interventions related to prescribing and duplication errors were the highest of all (30 and 29% respectively). Pharmacist interventions were recorded with a 95% acceptance rate. Cost analysis showed that pharmacist interventions saved around 105,115.88 US dollars. CONCLUSION: Clinical pharmacy services provided by integrated health system are a cost saving program. The cost saved per intervention for our study is around USD 37 which is more than another similar study which quoted USD 30.35 per intervention.

Potential of Tryptamine Derivatives as Multi-Target Directed Ligands for Alzheimer's Disease: AChE, MAO-B, and COX-2 as Molecular Targets.

Extensive research has been dedicated to develop compounds that can target multiple aspects of Alzheimer's disease (AD) treatment due to a growing understanding of AD's complex multifaceted nature and various interconnected pathological pathways. In the present study, a series of biological assays were performed to evaluate the potential of the tryptamine analogues synthesized earlier in our lab as multi-target-directed ligands (MTDLs) for AD. To assess the inhibitory effects of the compounds, various in vitro assays were employed. Three compounds, SR42, SR25, and SR10, displayed significant AChE inhibitory activity, with IC50 values of 0.70 µM, 0.17 µM, and 1.00 µM, respectively. These values superseded the standard drug donepezil (1.96 µM). In the MAO-B inhibition assay, SR42 (IC50 = 43.21 µM) demonstrated superior inhibitory effects as compared to tryptamine and other derivatives. Moreover, SR22 (84.08%), SR24 (79.30%), and SR42 (75.16%) exhibited notable percent inhibition against the COX-2 enzyme at a tested concentration of 100 µM. To gain insights into their binding mode and to validate the biological results, molecular docking studies were conducted. Overall, the results suggest that SR42, a 4,5 nitro-benzoyl derivative of tryptamine, exhibited significant potential as a MTDL and warrants further investigation for the development of anti-Alzheimer agents.

Synthesis, biological screening and docking studies of some indole derivatives as potential antioxidant.

The present study envisioned some antioxidant candidates having 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole (TRY), 3-(2-bromoethyl)indole (BEI) and 7-azindole (AI) nucleus. Derivatives of these indole molecules were synthesized and their scavenging activity for reactive oxygen species (ROS) investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. T3, T42 exhibited significant radical scavenging potential which is comparable to ascorbic acid (standard), while T36 appeared as most potent antioxidant by displaying better scavenging activity than standard molecule. Molecular docking study revealed good binding score and interactions of T36 with target human antioxidant enzyme (PDB code: 3MNG) validating the results of biological activity.

1,3-di-4-piperidylpropane derivatives as potential acetyl cholinesterase antagonists: Molecular docking, synthesis, and biological evaluation.

Acetylcholine esterase (AChE) is a key biological target responsible for the management of cholinergic transmission, and its inhibitors are used for the therapy of Alzheimer's disease. In the present study, a small library of molecules with 1,3-di-4-piperidylpropane nucleus were docked on AChE. The selected compounds were synthesized and evaluated for their enzyme inhibition. P25 and P17 expressed significantly higher AChE inhibition than standards with IC50 values of 0.591µM and 0.625µM, respectively. Binding mode of derivatives in the active site of AChE revealed dual binding of molecules in peripheral anionic site (PAS) and catalytic anionic site (CAS) of enzyme cavity.

Computation-based experimentation: Identification of piperazine containing antidepressants.

Depression, a common mental disorder, is one of the major contributors to the overall global burden with more than 264 million individuals affected worldwide. Monoamine oxidase inhibitors (MAOIs) have well-known efficacy for treating depression and other related disorders. Herein we report the implementation of extensive in-silico calculations to predict the mono-amine inhibitory potential of an in-house library of piperazine-based compounds. In this connection, a multistep virtual screening protocol based on pharmacophore modeling, molecular docking and Quantitative Structure-Activity Relationship (QSAR) was carried out by MOE. Further, to assess its ability to cross the blood brain barrier, ADME properties of the compounds were predicted. Compounds predicted the highest enzyme inhibition by QSAR was synthesized for experimental validation. Both the synthesized compounds (I15 and I21) presented good strength against Monoamine Oxidase in in vitro enzyme inhibitory activity.

Evaluation of anti-inflammatory and antibacterial potential of newly synthesized 4-(2-Keto-1-benzimidazollinyl) derivatives of piperidine.

Benzimidazole and its derivatives found variety of biological activities, for the searching of its potent anti-inflammatory analogues, we synthesized four novel 4-(2-keto-1-benzimidazollinyl) piperidine derivatives (Q1 to Q4) by refluxing piperidine with substituted imidazole and subjected to in-vitro anti-inflammatory (ROS, NO) and antibacterial activities, structures were elucidated using spectroscopic techniques. Results revealed that compound Q1 showed most effective anti-inflammatory activity with IC 50 7.6±1.3 µg/ml compared with standard Ibuprofen having IC50 11.2±1.9µg/mL. Compound Q3 showed good activity for Nitrite accumulation by stimulating macrophages test similar to standard NG Methyl L-arginine acetate with IC50 value 24.2±0.8µg/mL. The antibacterial activity of these compounds were evaluated against selected Gram+ve E. faecalis, C. diphtheriae, S. aureus and Gram -ve organism E. coli, Enterobacter aerogenes and P. aeruginosa. Synthesized compounds showed low to moderate level of antibacterial activity Q1 showed the highest antibacterial activity against Enterococcus faecalis and Escherichia coli with zone of inhibition 18mm and Q3 showed highest activity against Corynebacterium diptheriae (ZOI:18mm). Structure-activity relationship (SAR) study revealed that among all the synthesized compounds unsubstituted naphthalene (Q1) and phenyl (Q3) ring containing derivatives were most potent.

Molecular docking, synthesis and biological evaluation of phenacyl derivatives of 9-aminoacridine as anti-Alzheimer's agent.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder mainly characterized by progressive deterioration of memory and impaired cognitive function. The most promising approach for symptomatic relief of AD is to inhibit acetylcholinesterase (AChE). On the basis of this approach in-house library of 9-aminoacridine derivatives were constructed and allowed to docked against human acetylcholinesterase (hAChE) (PDB ID: 4EY7), using MOE 2018.01 and PyRx 0.9.2 (AutoDock Vina). Top ranked and best fitted molecules were synthesized by targeting the 9-amino group of aminoacridine with substituted phenacyl halides. Anti-Alzheimer's potential was checked by in vitro AChE inhibition, antioxidant activity (DPPH scavenging ability) and fibril disaggregation. Subjected ligands suggested as promising multitargeted candidate with pronounced results in term of IC50 values (AChE inhibition 2.400-26.138µM), however, none of them showed potential towards fibril inhibition.

Synthesis of 9-Aminoacridine Derivatives as Anti-Alzheimer Agents.

In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides (RM1-RM6). Compounds were investigated for acetylcholinesterase and butyrylcholinesterase inhibition potential, considering these enzymes playing a key role in Alzheimer's disease. All derivatives showed better inhibition of enzymes than the standard galantamine, whereas except RM4, all exhibit better results than tacrine, a well-known acridine derivative used for the treatment of Alzheimer's disease.