Impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients: a prospective cohort study.

OBJECTIVES: Poor control of asthma in the majority of patients could be partly due to their lack of knowledge concerning disease management, its triggering agents and when to seek advice from the healthcare provider. This study aims to assess the impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients. DESIGN: A pre-post cohort study. SETTING: Outpatient department of a tertiary care hospital affiliated with Quaid-i-Azam University, Pakistan. PARTICIPANTS: Approximately 265 adult asthmatic patients selected through a spirometry process, aged ≥18 years, were approached. 240 patients gave consent to participate in the study and were divided into control and treatment groups. INTERVENTIONS: The educational intervention consisted of individual patient counselling using educational material with time varied according to each patient's comprehension and previous knowledge. PRIMARY AND SECONDARY OUTCOME MEASURES: Assessment consisted of a 14-item Asthma Self-Management Knowledge Questionnaire (ASMQ) quantifying a patient's self-management knowledge through an ASMQ score and its change following an educational intervention. RESULTS: Disease self-management knowledge was low with an average raw ASMQ score of 4.1 (max 14); which equates to a transformed score of 29.34 (max 100) and the proportion of patients who correctly answered more than 50% of questions were 16.7% preintervention. More than half of the participants (55%) did not know that asthma cannot be cured. The administration of educational intervention protocols resulted in significantly improved level of knowledge of asthma self-management (<0.001) in the treatment group (mean ASMQ score improved from 4.20 to 9.77). CONCLUSION: On baseline visit, patients possessed a poor knowledge about asthma self-management. Educational intervention protocols had a positive impact on improving patients' knowledge about disease self-management. This would suggest that education and self-management skills should be seen as an integral component of asthma management and should be incorporated in structured patient care to achieve optimal asthma control.

Evaluation of antioxidant and antimicrobial activities on various extracts of Himalayan medicinal plants.

The DPPH radical scavenging potentials of the fractions were determined in comparison to positive controls such as quercetin with EC50 = 4.12±1.27, ascorbic acid with EC50 = 6.20±1.67, gallic acid with EC50 = 4.75±1.24 and α-tocopherol with EC50 = 32.50±1.57 µg/mL. The experiment showed that aqueous fractions of the bark extracts of Abies pindrow (fraction: C2) and Cedrus deodara (fraction: E2) showed significantly lower EC50 values of 2.5±0.5 and 2.5±0.6 µg/mL, respectively. In reducing power assay, lower EC50 values of 5.5 and 4.5µg/mL were recorded for the aqueous fraction (fraction: C 2) and final residue (fraction: C5), of Abies pindrow, respectively. The ethyl acetate, acetone and final fractions of knot wood of Picea smithiana were found significantly active against all bacterial strains. Of the most sensitive fractions towards all the fungal strains was ethyl acetate fraction obtained from the bark of Cedrus deodara with a zone of inhibition ranging from 75 to 88 % that was more than the standard fluconazole.

Robust therapeutic potential of carbazole-triazine hybrids as a new class of urease inhibitors: A distinctive combination of nitrogen-containing heterocycles.

The inhibition of urease enzyme is very important as it plays a key role in the treatment of several urinary and gastrointestinal tract infections. This enzyme provides a suitable environment for Helicobacter pylori at the low pH of the stomach, a causative agent of gastric and peptic ulcer that may lead to cancer. In agriculture, the high urease content causes environmental and economic problems. In this pursuit, given the well-established importance of integrated pharmacophores in medicinal chemistry and to explore new inhibitors of urease featuring two distinct heterocyclic functionalities, we herein report a facile synthesis of carbazole-triazine hybrids (3a-j). These new propeller-shaped chemical scaffolds were evaluated for their urease inhibitory potential in order to identify suitable leads. The initial structure-activity survey work guided through in vitro bioactivity results recognized 3e and 3f as new starting point hits incorporating bulky iodo (3e) and strong electron-withdrawing nitro (3f) groups at the para-position of aryl amine component. The potent compounds (3e &3f) exhibited the highest activity with IC50 values of 5.6 and 6.7 µM, respectively. In the molecular docking analysis, these compounds depicted excellent binding interactions with the active site residues. The key interactions observed include hydrogen bonding, π-π interactions, π-cation and nickel atom coordination to the triazine nitrogen of both inhibitors.

Exploring biological efficacy of coumarin clubbed thiazolo[3,2-b][1,2,4]triazoles as efficient inhibitors of urease: A biochemical and in silico approach.

Combating several pathological conditions associated with ureolytic enzyme (urease) remains a formidable challenge because of the lack of effective and safe drug therapies. In this regard, the development of potent inhibitors of urease could be considered as a promising remedy. Herein, we report a new library of structurally diverse hybrid heteroaromatics featuring coumarin and thiazolotriazole motifs in one combined unit. These new chemical scaffolds accessed through the integration approach were shown to inhibit the enzyme urease from jack bean at variable efficacies. An initial structure-activity relationship analysis guided through the variation of several functional groups at the aryl ring connected to the thiazole core revealed compound 6o (IC50 = 4.35 ±â€¯0.18 µM) as the most potent inhibitor. The inhibitory strength of 6o was 5-fold compared to thiourea (standard; IC50 = 20.8 ±â€¯0.59 µM). In the molecular docking analysis, 6o was stabilized in the active pocket through various binding interactions. The presence of an amino moiety at the meta position of the phenyl ring facilitates hydrogen bonding with the sulfhydryl group of Cys322 (2.11 Å) in addition to an interaction observed between the thiazole sulfur and nickel atoms present in the active site. Moreover, this amino group also interacts with the carbonyl oxygen of Ala366 at a distance of 2.75 Å. The chromenone moiety of compound 6o is stabilized by the side chains of various amino acid residues including Ala279, Thr301, Pro303, Thr304, His315 and Met367.

Developing new hybrid scaffold for urease inhibition based on carbazole-chalcone conjugates: Synthesis, assessment of therapeutic potential and computational docking analysis.

Although a diverse range of chemical entities offering striking therapeutic potential against urease enzyme has been reported, the key challenges (toxicity and safety) associated with these inhibitors create a large unmet medical need to unveil new, potent and safe inhibitors of urease enzyme. In this pursuit, the present study demonstrates the successful synthesis of carbazole-chalcone hybrids (4a-n) in good yields. The evaluation of the preliminary in vitro biological results showed that selected members of the investigated library of hybrid compounds possess excellent urease inhibitory efficacy. In particular, compounds 4c and 4k were the most potent inhibitors with lowest IC50 values of 8.93 ±â€¯0.21 and 6.88 ±â€¯0.42 µM, respectively. Molecular docking analysis of the most potent inhibitor 4k suggests that the compound is fitted neatly at the active site interface and mediates interaction with both nickel atoms present in the active site. Several other obvious interactions including metal-carbonyl contact, hydrogen bonding and hydrophobic interactions were also observed, playing a crucial part in the stabilization of 4k in the active site of urease.

Formulation and in vitro evaluation of directly compressed controlled release tablets designed from the Co-precipitates.

Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance. In present study, controlled release co-precipitates of Metoprolol Tartrate and Losartan Potassium were prepared by solvent evaporation method using polymers such as Eudragit RL 100 and Carbopol 974PNF and controlled release tablets were directly compressed into tablets. In-vitro dissolution of controlled release co-precipitates were performed by USP Method-II (paddle method) and tablets were evaluated by USP Method-I (rotating basket method) in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature was maintained constant at 37±1.0°C and the rotation speed of paddle and basket was kept constant at 100rpm. Drug release mechanisms were determined by applying Power Law kinetic model. The difference and similarity of dissolution profiles test formulations with reference standards were also determined by applying difference factor (f1) and similarity factor (f2). The results showed that the controlled release co-precipitates with polymer Eudragit RL 100 of both the drug extended the drug release rates for 10 hours and those having polymer Carbopol 974P NF extended the drug release rates for 12 hours. The controlled release tablets prepared from controlled release co-precipitates extended the drugs release up to 24 hours with both the polymers. The drug was released by all tests anomalous non fickian mechanism except F1 and F5 do not follow Power Law. The f1 and f2 values obtained were not in acceptable limits except F15 whose values were in acceptable limits. It is concluded from the present study that polymers (Eudragit RL 100 and Carbopol 974P NF) can be efficiently used in development of controlled release dosage forms having predictable kinetics.

Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles.

In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a-o) and coumarin-oxadiazole 11(a-h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 µM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 µM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 µM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 µM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of -10.19, -9.97, -9.68, and -11.03 Kcal.mol-1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a-h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of -9.9, -7.4, and -8.2 Kcal.mol-1, respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction.

A new entry into the portfolio of α-glucosidase inhibitors as potent therapeutics for type 2 diabetes: Design, bioevaluation and one-pot multi-component synthesis of diamine-bridged coumarinyl oxadiazole conjugates.

Diabetes mellitus (DM), a chronic multifarious metabolic disorder resulting from impaired glucose homeostasis has become one of the most challenging diseases with severe life threat to public health. The inhibition of α-glucosidase, a key carbohydrate hydrolyzing enzyme, could serve as one of the effective methodology in both preventing and treating diabetes through controlling the postprandial glucose levels and suppressing postprandial hyperglycemia. In this context, three series of diamine-bridged bis-coumarinyl oxadiazole conjugates were designed and synthesized by one-pot multi-component methodology. The synthesized conjugates (4a-j, 5a-j, 6a-j) were evaluated as potential inhibitors of glucosidases. Compound 6f containing 4,4'-oxydianiline linker was identified as the lead and selective inhibitor of α-glucosidase enzyme with an IC50 value of 0.07 ±â€¯0.001 µM (acarbose: IC50 = 38.2 ±â€¯0.12 µM). This inhibition efficacy was ∼545-fold higher compared to the standard drug. Compound 6f was also emerged as the lead molecule against intestinal maltase-glucoamylase with good inhibition strength (IC50 = 0.04 ±â€¯0.02 µM) compared to acarbose (IC50 = 0.06 ±â€¯0.01 µM). Against ß-glucosidase enzyme, compound 6 g was noted as the lead inhibitor with IC50 value of 0.08 ±â€¯0.002 µM. Michaelis-Menten kinetic experiments were performed to explore the mechanism of inhibition. Molecular docking studies of the synthesized library of hybrid structures against glucosidase enzyme were performed to describe ligand-protein interactions at molecular level that provided an insight into the biological properties of the analyzed compounds. The results suggested that the inhibitors could be stabilized in the active site through the formation of multiple interactions with catalytic residues in a cooperative fashion. In addition, strong binding interactions of the compounds with the amino acid residues were effective for the successful identification of α-glucosidase inhibitors.

To study the influence of different grades of Ethylcellulose ether derivative polymer Ethocel® and co-excipient on drug release profile of controlled release matrix tablet of acarbose.

The aim of the study presented is to formulate and evaluate Acarbose controlled release matrix tablets by means of different grades of polymer Ethocel and different co-excipients with the intention to see their effects on drug release profile during in vitro dissolution studies. Controlled release dosage forms is gaining rapid popularity due to its positive aspect of reduction in dosage frequency and curtailing side effects. Controlled released tablets of Acarbose were prepared by direct compression method, using Ethocel® Standard 7 Premium and Ethocel® Standard 7 FP premium polymer. The effect of co-excipients including hydroxypropyl methylcellulose (HPMC), Carboxymethyl cellulose (CMC) and starch on the drug placing 30% lactose were also examined. In-vitro studies were carried out with the help of phosphate buffer (pH 7.4) as dissolution medium. Drug release mechanism was assessed by applying various kinetic models. Similarly / dissimilarity factor f2/ f1 were applied for determination of dissolution profile of the test and reference formulations. Physiochemical characteristics were in the USP satisfactory limits. Conventional Acarbose tablet released 97% of the drug within 2 hrs. Ethocel® Standard 7 premium and Ethocel® standard 7 FP released 59.9% and 47.01% of the drug within 6 and 99.9% and 97% within 24 hours, respectively. This effect possibly has been achieved owing to the smaller particle size of the Ethocel® Standard 7 FP premium which show evidence of anomalous, non-fickian release kinetics. Co-excipients like HPMC, CMC and starch augment the drug release rates from the matrices which may be attributed to their hydrophilic nature. Ethocel® Standard 7 Premium and Ethocel® Standard premium 7 FP polymers show a promising response in fruitful production of controlled release tablets by direct compression method.

Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets.