Objective: Experimental pain models in human healthy volunteers are advantageous for early evaluation of analgesics. All efforts to develop nonsteroidal anti-inflammatory drugs (NSAIDs) which are devoid of gastrointestinal and cardiovascular system effects are still far from achieving a breakthrough. Hence we evaluated the analgesic activity of an ayurvedic drug, Boswellia serrata by using validated human pain models which has shown its analgesic activity both in-vitro and preclinical studies to evaluate the analgesic activity of single oral dose (125 mg, 2 capsules) of Boswellia serrata compared to placebo using mechanical pain model in healthy human subjects. Materials and Methods: After taking written informed consent, twelve healthy subjects were randomized (1:1) to receive single oral dose of Boswellia serrata (Shallaki^® ) 125 mg, 2 capsules or identical placebo in a crossover design. Mechanical pain was assessed using Ugo basile analgesymeter (by Randall Selitto test) at baseline and at 1 hr, 2 hrs and 3 hrs after test drug administration. Pain Threshold force and time and Pain Tolerance force and time were evaluated. Statistical analysis was done by paired t-test. Results : Twelve healthy volunteers have completed the study. Mean percentage change from baseline in Pain Threshold force and time with Boswellia serrata when compared to placebo had significantly increased [Force: 9.7 ± 11.0 vs 2.9 ± 3.4 (P = 0.05) and time: 9.7 ± 10.7 vs 2.8 ± 3.4 (P = 0.04)] at third hr. Mean Percentage change from baseline in Pain Tolerance force and time with Boswellia serrata when compared to placebo had significantly (P ≤ 0.01) increased at 1 hr, 2 hrs and 3 hrs. Conclusion : In the present study, Boswellia serrata significantly increased the Pain Threshold and Pain Tolerance force and time compared to placebo. Both study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug.

Objective: To determine the quality of prescribing in hypertension in primary and secondary health care settings using the Prescription Quality Index (PQI) tool and to assess the reliability of this tool. Materials and Methods: An observational cross-sectional study was carried out for 6 months in order to assess quality of prescribing of antihypertensive drugs using Prescription Quality Index (PQI) at four primary (PHC) and two secondary (SHC) health care facilities. Patients attending these facilities for at least 3 months were included. Complete medical history and prescriptions received were noted. Total and criteria wise PQI scores were derived for each prescription. Prescriptions were categorized as poor (score of ≤31), medium (score 32-33) and high quality (score 34-43) based on PQI total score. Psychometric analysis using factor analysis was carried out to assess reliability and validity. Results: Total 73 hypertensive patients were included. Mean age was 61.2 ± 11 years with 35 (48%) patients above 65 years of age. Total PQI score was 26 ± 11. There was a significant difference in PQI score between PHC and SHC (P < 0.05) Out of 73 prescriptions, 43 (59%) were of poor quality with PQI score <31. The value of Cronbach's α for the entire 22 criteria of PQI was 0.71 suggesting good reliability of PQI tool in our setting. Conclusions: Based on PQI scores, quality of prescribing in hypertensive patients was poor, somewhat better in primary as compared to secondary health care facility. PQI is reliable for measuring prescribing quality in hypertension in Indian set up.

Objective: To estimate and compare the cost-effectiveness and safety of nebivolol with sustained-release metoprolol in reducing blood pressure by 1 mm of Hg per day in hypertensive patients. Materials and Methods: This was a prospective, randomized, open label, observational analysis of cost-effectiveness, in a questionnaire-based fashion to compare the cost of nebivolol (2.5 mg, 5 mg, 10 mg) and sustained released metoprolol succinate (25 mg, 50 mg, 100 mg) in hypertensive patients using either of the two drugs. A total of 60 newly detected drug naïve hypertensive patients were considered for the comparison, of which 30 patients were prescribed nebivolol and the other 30 were prescribed metoprolol succinate as per the recommended dosage. Based on the data, statistical analysis was carried out using GraphPad Prism 5 and MS Excel Spreadsheet 2007. Result: The cost of reducing 1 mm of Hg blood pressure per day with nebivolol was 0.60, 0.70, and 1.06 INR, whereas that of metoprolol succinate was 0.93, 1.18, and 1.25 INR at their respective equivalent doses, hence significantly lower with the nebivolol group as compared to the metoprolol group (P < 0.05). Conclusion: This pharmacoeconomic analysis shows that nebivolol is more cost-effective as compared to metoprolol when the cost per reduction in blood pressure per day is considered. This may affect the patients economically during their long-term use of these molecules for the treatment of hypertension.

Objective: To document the significant sustained virological response with supervised conventional interferon α and ribavirin therapy in hepatitis C virus (HCV)-infected patients, this study was planned. Materials and Methods: Sixty chronic hepatitis C naive patients were included in this study. Complete blood counts, prothrombin time, ALT, AST, and qualitative HCV RNA were done. Conventional interferon (INF) α2a, 3MIU, S.C and ribavirin 1000 mg PO was given as supervised therapy for 24 weeks in genotype 3 and 48 weeks in genotype 1 and 4 HCV patients. Qualitative HCV RNA was repeated at 12 weeks, 24 weeks for HCV infections with genotype 1, 2, 3 and 4, at 48 weeks for genotype 1 and 4, and thereafter 6 months after completion of treatment. End virological and sustained virological responses were observed. Results: Out of 60 patients, 55 completed the study. Five patients were lost to follow-up. Overall SVR was seen in 47 patients (85.4%) and 4 patients had relapses. Conclusion: Significant sustained virological response rates were seen in patients with supervised conventional INF α2a and ribavirin therapy.

Objective: To assess the cardiovascular safety of two commonly prescribed atypical antipsychotics risperidone (RSP) and olanzapine (OZP) in schizophrenic patients, using electrocardiography (ECG) and Blood Pressure (BP). Materials and Methods: This was a 10-week prospective open label, observational study, carried out in a newly diagnosed 64 schizophrenic patients receiving either RSP or OZP. RSP (n = 32) was started with dose of 2 mg/day and increased to 4 mg/day after 2 weeks, whereas OZP (n = 32) was started at a dose of 5 mg/day and was increased to 10 mg/day after 2 weeks. Heart rate (HR), ECG parameters (PR, RR, QRS, QT intervals and QTc and QTd) and BP (systolic and diastolic in supine and standing position) were recorded at baseline (before drug therapy)) and during follow-up visits at 2(I), 6(II) and 10(III) weeks. Results: In the RSP group, at II and III follow-ups, a significant increase in the HR (P = 0.018, P = 0.011 respectively) as well as in QTc (P = 0.025, P = 0.015, respectively) was observed when compared to the basal values. In the OZP group, diastolic BP was significantly decreased in standing position at II and III follow-ups (P = 0.045 and P = 0.024, respectively) compared to the basal values. When the two groups were compared with each other, no significant differences were observed in the changes of HR, PR, QRS, QT, RR, QT, QTd and SBP (supine and standing position); and DBP (supine position). However, DBP in standing position showed a significant decrease in the OZP group at II and III follow-up (P = 0.036 and P = 0.016, respectively) compared to the RSP group. Conclusions: Patients treated with OZP are at higher risk to develop postural hypotension as compared with RSP; hence RSP could be better tolerated by patients taking antihypertensive drugs as compared with OZP whereas OZP would have a safer cardiac profile.

Objectives: Lafutidine is a new H ₂ -blocker in India claimed to be more potent and effective than existing H ₂ -blockers. Proton pump inhibitors (PPIs), by virtue of their mechanism of action, have greater efficacy than H ₂ -blockers in gastric acid suppression. However, clinical trials comparing H ₂ -blockers directly with PPIs are limited. We carried out a head-to-head comparison of the effectiveness of lafutidine versus the PPI pantoprazole in uninvestigated dyspepsia [CTRI/2013/12/004261]. Materials and Methods: A prospective, open label, randomized, controlled trial was conducted in a tertiary care hospital. Ambulatory adult patients with dyspepsia, not yet subjected to endoscopy, were recruited if they had at least moderately severe symptoms, defined as a score of ≥ 4 on a 7-point Global Overall Symptom (GOS) Scale. Those with alarm features or significant comorbidity were excluded. Subjects received either once daily lafutidine 10 mg or pantoprazole 40 mg, orally, for 8 weeks. Reflux, dysmotility and pain scores were assessed by Modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSGERD), and quality of life (QoL) by SF-8 scale. The latter had physical and mental components summarized by physical component summary score (PCS) and a mental component summary score (MCS). Results: Of 122 patients enrolled, data of 57 on lafutidine and 60 on pantoprazole were analyzed. At 4 weeks, proportion of subjects responding (GOS score ≤ 2) in the two arms (lafutidine 45.61% vs. pantoprazole 48.33%, P = 0.854) or showing symptom resolution (GOS score ≤ 1) (lafutidine 12.28% vs. pantoprazole 5.00%; P = 0.197) were comparable. Similarly at 8 weeks, both responder (lafutidine 52.63% vs. pantoprazole 56.67%; P = 0.712) and symptom resolution proportions (lafutidine 33.33% vs. pantoprazole 30%; P = 0.843) were comparable. Total score on mFSSGERD scale, as well as all its three component scores, and PCS and MCS scores on QoL SF-8 scale showed improvement but no statistically significant difference between the two arms. Tolerability of both drugs was excellent. Conclusions : Lafutidine is well-tolerated and there is no clinically worthwhile difference between the two drugs in the empirical treatment of uninvestigated dyspepsia.

Objective: The aim of this study was to evaluate the pattern of fixed dose combinations (FDCs) in Ahmedabad, a city in western part of India. Materials and Methods: Over a period of 24 months, prescriptions were collected from 24 pharmacy stores across 6 zones of Ahmedabad city. The information was recorded in pre-formed Data Record Form after written consent from the patients (or relative (s) of the patients). The pattern of use of FDC, rationality and seasonal variation in their use were analyzed. At the end of study, results were analyzed using Chi-square test. Results: Out of the total 1170 prescriptions, 941 (80.3%) contained 1647 FDC formulations. The average number of FDCs prescribed was 1.41 ± 1.04 (mean ± SD). The FDCs were more frequently prescribed in the age group of 31 to 40 years (23.7%) and in males (54.4%). FDCs were most commonly prescribed by oral route (92.7%). As per drug category analysis, a higher number of FDCs containing nutritional supplements (20.2%), and those for CNS (18.1%) complaints were prescribed. A seasonal analysis showed that FDCs were commonly prescribed for respiratory complaints (23.4%), central nervous system (CNS) complaints (20.3%) and as nutritional supplements (22.4%) in winter, monsoon and summer months, respectively. Only 5.8%, 9.8% and 10.9% FDCs prescribed were included in WHO (2010), National (2011) and Gujarat State (2011) Essential Medicines Lists (EML), respectively (P < 0.0001). Irrational FDCs that are banned or FDCs containing irrational active ingredients were 1343 (81.5%) and 203 (12.3%), respectively. Conclusion: FDCs are widely prescribed with seasonal influence in their use. FDCs containing banned or controversial ingredients are prescribed widely.

Objective: Tongxinluo (TXL) is a traditional Chinese medicine (TCM). It is used to treat coronary heart disease and atherosclerosis. We investigated the effects of TXL on the neointima formation and expression of inflammatory cytokines in rats after carotid artery balloon injury. Materials and Methods: Male Sprague-Dawley rats were randomly divided into four groups: sham operation group (Sham, n = 15), balloon injury group treated with vehicle (Control, n = 15), TXL low-dose group treated with TXL of 0.5 g/kg/d (TXL-L, n = 15), and TXL high-dose group treated with TXL of 1.0 g/kg/d (TXL-H, n = 15). TXL was given by gavage daily. 14 days after injury`, the levels of serum nitric oxide (NO), endothelin-1 (ET-1), monocyte chemoattractant protein-1 (MCP-1), and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated. The morphology of carotid artery tissue was observed with hematoxylin-eosin staining. Expressions of MCP-1 and ICAM-1 in the artery were detected by real-time polymerase chain reaction (RT-PCR) and western blotting. Results: 14 days after injury, a significant increase in concentrations of serum ET-1, MCP-1, and sICAM-1 (P < 0.05), as well as a significant decrease in NO serum level were observed in rats subjected to artery injury compared to the sham rats (P < 0.05). TXL significantly decreased ET-1, MCP-1 and sICAM-1 serum levels (P < 0.05), whereas significantly increased NO serum level compared with the control (P < 0.05). TXL significantly reduced the neointimal thickening at day14 after injury (P < 0.05). In addition, TXL significantly reduced mRNA and protein expressions of ICAM-1 and MCP-1 in injured artery (P < 0.05). Conclusions: This study demonstrates that TXL is effective in improving endothelial function, attenuating neointimal formation of artery after balloon injury, and reducing expression of inflammatory cytokine MCP-1 and ICAM-1. It may be a useful agent for protecting the artery against injury.

Aim: Clitoria ternatea Linn. (C. ternatea) is an Ayurvedic herb traditionally used as medicine to relieve inflammatory, rheumatism, ear diseases, fever, arthritis, eye ailments, sore throat and body ache. This study aims to evaluate and elucidate the possible mechanism underlying the antinociceptive action of methanolic extracts of C. ternatea leaf and root using several antinociception models. Materials and Methods: The different antinociception models such as hot plate, tail-flick and formalin tests were used along with naloxone (a non-selective opioid antagonist) to establish the antinociceptive activity of both leaf and root extracts. Results: Both C. ternatea leaf and root extracts markedly demonstrated antinociceptive action in experimental animals. Results of formalin test showed that the antinociceptive activity of the extracts may be mediated at both central and peripheral level. Moreover, the results of hot plate and tail-flick tests further implies that C. ternatea root extract mediates antinociceptive activity centrally at supraspinal and spinal levels whereas, the C. ternatea leaf extract's antinociceptive activity is mediated centrally at supraspinal level only. It is believed that the opioid receptors are probably involved in antinociceptive activity of both C. ternatea root extract. Conclusions: Our studies support the traditional use of C. ternatea leaf and root against pain. The extracts can also be utilised as a new source of central analgesics in treatment of pain.

Objective: 1,3,4-oxadiazole ring is a versatile moiety with a wide range of pharmacological properties. The present work deals with the synthesis and evaluation of the anti-inflammatory activity of two novel 2,5-disubstituted-1,3,4-oxadiazoles (OSD and OPD). Materials and Methods: Carrageenan-induced rat hind paw edema was employed as an acute model of inflammation. For evaluating sub-acute anti-inflammatory activity, carrageenan-induced inflammation in rat air pouch was employed. Complete Freund's adjuvant-induced arthritis in rats was used as a model of chronic inflammation. To evaluate in vitro anti-inflammatory activity, lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used. Results: OSD (100 mg/kg) reduced carrageen-induced paw edema by 60%, and OPD (100 mg/kg) produced a modest 32.5% reduction. OSD also reduced leukocyte influx and myeloperoxidase in carrageenan-induced rat air pouch model. In complete Freund's adjuvant-induced arthritis model, both OSD and OPD (200 mg/kg for 14 days) reduced paw edema and NO levels. In LPS-stimulated RAW264.7 cells, OSD and OPD inhibited formation of nitric oxide and reactive oxygen species, with OPD showing a better activity in comparison to OSD. Conclusions: OSD was the better of the two compounds in in vivo models of inflammation. The o-phenol substitution at position 2 of oxadiazole ring in OSD may be responsible for its better in vivo anti-inflammatory activity. The ability of the compounds to inhibit LPS-induced pro-inflammatory mediator release suggests an anti-inflammatory mechanism targeting LPS-TLR4-NF-κB signalling pathway, which needs to be explored in detail. The disparate efficacy in vitro and in vivo also requires in-depth evaluation of the pharmacokinetics of these novel oxadiazoles.

Objective: The objective of this study was to evaluate the cardioprotective effect of herbal bioactive compound ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy, in experimental animals. Materials and Methods: Ammonium glycyrrhizinate (50, 100, 200 mg/kg, p.o.) was administered for four weeks in albino rats. Cardiomyopathy was induced with a dose of 2.5 mg/kg i.p. of doxorubicin on 1 ^th , 7 ^th , 14 ^th , 21 ^th , 28 ^th day in the experimental animals. At the end of the experiment, on 29 ^th day, serum and heart tissues were collected and hemodynamic, biochemical and histopathological studies were carried out. Results: Administration of doxorubicin in normal rats showed significant (P < 0.001) changes in body weight, feed intake, urine output, hemodynamic parameters like (blood pressure, heart rate, cardiac output) and in lipid profile (cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein) indicating cardiomyopathy symptoms. Animals treated with ammonium glycyrrhizinate significantly (P < 0.05) decreased triglyceride, cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels. Moreover, high density lipoprotein (HDL) levels increased in rats treated with ammonium glycyrrhizinate as compared with the normal group. Conclusion: Ammonium glycyrrhizinate is effective in controlling serum lipid profile and cardiac complications in experimentally induced cardiomyopathy in animals.

Aim: The study was designed to investigate the chemopreventive potential of flavonoidal fractions of Apium leptophyllum fruits (FFALF) on Swiss mice. Materials and Methods: Skin tumor or papilloma was developed by topical application of DMBA (25 μg in 0.1 ml acetone) on intrascapular region of mice, twice weekly for 8 weeks. The animals were divided into six groups: Group I (vehicle control); group II (FFALF control, 5 mg/kg); group III (carcinogenic control, DMBA treated initially for 8 weeks); and group IV, V and VI as pre-treated group (FFALF 5, 10 and 20 mg/kg respectively for 16 weeks along with DMBA treatment). After the 16 ^th week of treatment; the tumor morphology, skin histopathology, and biochemical and antioxidant biomarkers were measured and compared with carcinogenic control as well as vehicle control. Results: The co-administration of FFALF with DMBA-treated groups showed significant (P ≤ 0.001) prevention against skin papilloma and normalized the status of lipid peroxidation with antioxidant biomarkers in a dose-dependent manner as compared to carcinogenic control. Conclusions: Thus, the present study suggests that the FFALF is non-carcinogenic and has chemopreventive potential on DMBA-induced carcinogenesis in mouse, which may be due to the modulation of cutaneous lipid peroxidation or enhancement of total antioxidant capacity.

Objectives: To analyze the impact of various drugs used in conservative therapy on renal failure and mortality in hepatorenal syndrome (HRS) at a tertiary care teaching hospital. Materials and Methods: Retrospective review of hospital admission records was conducted for case records with HRS as diagnosis. Demographic and clinical data and drug utilization pattern were collected in a pre-designed patient information sheet. Impact of various drugs especially hepatoprotector antioxidant, silymarin, on survival benefits in terms of number of patients alive, change in mean arterial pressure (MAP) and change in serum creatinine at the end of treatment period were estimated by univariate and followed by multivariate analysis. Results: Of the total 89 case records, 31 met the eligibility criteria and were included in the analysis. On multivariate analysis, a significant correlation between use of intravenous fluids (IVFs) and survival benefits was observed (P < 0.05); wherein patients treated with IVFs had an increase in log odds of survival by 2.42 (95% CI = 1.06 to 121.13) as compared to patient not treated with IVF. However, MAP was not affected by any of the treatment modalities. While change in serum creatinine level was not significantly (P = 0.06, regression correlation = −0.3) correlated with duration of treatment with IVFs. Conclusion: Use of IVFs may be associated with better short-term survival benefits and favor HRS reversal. Use of silymarin as hepatoprotector antioxidant has no beneficial effects on HRS reversal or survival benefits.

Objective: This prospective observational study was carried out to identify the prevalence and Severity of ADRs of antidepressant in a tertiary care teaching hospital. Materials and Methods: Patients prescribed with at least one antidepressant were randomly selected and monitored for adverse drug reactions (ADRs), irrespective of their age and gender. Results: Of the 401 patients who received antidepressants, 170 patients (42.39%) experienced 204 ADRs. Selective serotonin receptor inhibitors (SSRIs) [110 (53.92)] was the most common therapeutic class of drugs associated with ADRs. Gastrointestinal system [54 (26.47)] was most commonly affected system organ class. Dry mouth (n = 30) and diaphoresis (n = 21) were the most frequently reported ADRs. As assessed by the World Health organization (WHO) probability scale, 61% of the ADRs were 'probable' causality. Among all the ADRs, 22.54% (46) were preventable. Majority of the ADRs [(n = 184) 90.17%] were 'mild' in their severity. Conclusion: In this study, incidence of adverse reaction to antidepressants was 42.3% were the most comman SSRI inplicated drug group for the ADRs.

Medication errors may occur at any point during patient care in the health care system. Drug interaction in known with macrolide antibiotics and ranolazine and is primarily related to effects on the cytochrome P4503A (CYP3A) metabolic pathway. This case highlights medication errors that resulted in rare debilitating neurological adverse effects of ranolazine in an elderly due to drug interaction with clarithromycin.

Warfarin is the most common and cheap oral anticoagulant currently used in clinical practice. A high inter-individual variation is seen in the response to warfarin. Recently, pharmacogenetics has gained importance in managing patients on warfarin, both in predicting the optimum required dose as well as in decreasing the risk of bleeding. This case report is a description of a 49-year-old patient who had a lethal subdural hematoma with low-dose warfarin. He was subsequently found to have CYP2C9 gene polymorphism (*1/*3). This case report stresses the importance of pre-prescription assessment of genetic analysis for those initiated on warfarin.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is an adverse drug reaction which has been reported to be caused by various drugs. In this report, we describe a case induced by ranitidine, a drug which has not been previously reported to cause SDRIFE.

Adalimumab is a drug used in the treatment of refractory psoriasis. We present a case of a 55-year-old male patient who developed petechiae and purpura after the ninth dose of adalimumab therapy. The results of laboratory investigations revealed factor XI (F.XI) deficiency. It should be recognized that F XI deficiency may develop in patients using long-term adalimumab, leading to increased risk of bleeding.

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastrointestinal (GI) bleed. Co-administration of proton pump inhibitors (PPIs) has been widely suggested as one of the strategies to prevent these GI complications among NSAIDs users. Herein, we present a case of severe GI bleeding in a patient taking fixed dose combination (FDC) of rabeprazole (20 mg) and diclofenac sodium (100 SR).

Thalidomide developed in 1954 for morning sickness had proven to be a teratogen and hence was withdrawn from market. Resurgence of thalidomide began as an immunomodulator when it was shown to be effective in the management of multiple myeloma and many conditions like erythema nodosum leprosum, graft versus host disease, recurrent aphthous ulcers etc. We report a case of Stevens Johnson syndrome-toxic epidermal necrolysis developing in an elderly male who was prescribed thalidomide after being diagnosed with multiple myeloma.

Levetiracetam (LEV) is a relatively newer antiepileptic drug with novel mechanism of action. It was introduced to the market in the year 2000. Pre-marketing clinical trials of the drug reported good tolerability with a wide safety margin. On post-marketing updates, there are few reports of psychosis after treatment with the drug. Here, we report a case of 52-year-old epileptic man who developed acute, reversible psychosis within 3 days of initiation of treatment. The drug was prescribed at a dose of 500 mg per day. After 3 days of treatment, the patient developed visual hallucinations, mood swings, withdrawal and suspicious behavior. Delirium was ruled out as there was no fluctuation in his sensorium or focal neurological deficits. His lab investigations for electrolytes, renal function test, thyroid, liver function and other related tests levels were within normal limits. A diagnosis of LEV induced psychosis was reached based on clinical judgment and causality assessment.