Shalini Chawla

SGLT2 Inhibitors: A New Emerging Therapeutic Class in the Treatment of Type 2 Diabetes Mellitus

The incidence of type 2 diabetes mellitus is increasing worldwide. The existing therapeutic classes of antidiabetic drugs are not adequately effective in maintaining long‐term glycemic control in most patients, even when used in combination. One emerging novel therapeutic class of antidiabetic drugs is sodium glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 accounts for 90% of the glucose reabsorption in the kidney. The SGLT2 inhibitors increase urinary excretion of glucose and lower plasma glucose levels in an insulin‐independent manner. Dapagliflozin, the most prominent molecule in this class, is currently in a phase III clinical trial. Other members of this class (eg, sergliflozin, remogliflozin) are also in different phases of clinical trials. This class of novel agents can effectively control blood sugar level without producing weight gain or hypoglycemia. Results of ongoing phase III clinical trials are crucial to determine whether the risk‐benefit ratio will allow approval of this new class of drugs for the management of type 2 diabetes mellitus.

Recent advances in antiretroviral drugs

Importance of the field: Acquired immunodeficiency syndrome (AIDS) is one of the leading causes of death worldwide. Although the combination therapies of highly active antiretroviral therapy (HAART) have significantly contributed to virological suppression, improved immune function and quality of life, issues such as tolerability, drug–drug interactions and cross-resistance amongst members of a particular drug class still pose a significant barrier to long-term successful treatment. There is a constant need for newer anti HIV drugs with increased potency and improved pharmacokinetic properties either in the existing classes or drugs from new classes that target several new steps in HIV replication cycle. Areas covered in this review: The authors have discussed newer antiretroviral drugs belonging to second-generation nucleoside analog reverse transcriptase inhibitors (amdoxovir, elvucitabine, apricitabine, racivir), non-nucleoside analog reverse transcriptase inhibitors (etravirine, rilpivirine), protease inhibitors (darunavir, tipranavir) as well as emerging new classes, i.e., fusion inhibitors (enfuvirtide, sifuvirtide), CCR5 inhibitors (maraviroc, vicriviroc, PRO 140, PRO 542), CD4-receptor inhibitors (ibalizumab), integrase inhibitors (raltegravir, elvitegravir, GSK-1349572), maturation inhibitors (bevirimat), cobicistat (pharmacoenhancer), lens epithelium-derived growth factor inhibitors and capsid assembly inhibitors. What the reader will gain: The reader will gain an understanding of the mechanism of action, mechanism of resistance, stages of development and important clinical trials related to the newer antiretroviral drugs and future potential of these drugs. Take home message: The initial clinical trial data of these newer drugs are very encouraging for the long-term successful control of HIV in both treatment-naïve and treatment-experienced patients.

Effect of addition of either sitagliptin or pioglitazone in patients with uncontrolled type 2 diabetes mellitus on metformin: A randomized controlled trial

Objective: To compare and study the dipeptidy1 peptidase-4 (DPP-4) inhibitors in combination with metformin against established combination therapies. Materials and Methods: This 16-week study was designed to compare sitagliptin versus pioglitazone as add-on therapy in patients of type 2 diabetes mellitus inadequately controlled with metformin alone. Fifty-two patients were randomized into two groups to receive either sitagliptin 100 mg (group 1) or pioglitazone 30 mg (group 2) in addition to metformin. The primary efficacy end point was change in HbA1c. Secondary end points included change in fasting plasma glucose (FPG), body weight and lipid profile. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire. Both the groups had a significant decrease in HbA1c. Results: There was no significant difference between mean reductions in FPG in both the groups. There was a significant decrease in the mean body weight and body mass index in group 1 in contrast to the significant increase in the same in group 2. Both the treatment groups reported a significant decrease in High-density lipoprotein (HDL-C) and Triglyceride. Conclusion: Sitagliptin was well tolerated without any incidence of hypoglycemia. It was concluded that sitagliptin as an add-on to metformin is as effective and well tolerated as pioglitazone.

Antidepressant-Like Activity of Tramadol in Mice

Objective: To evaluate antidepressant-like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10, 20, and 40 mg/kg, i.p.) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug-treated mice was recorded in forced swim test (FST). The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p.), administered for seven successive days. Results: Tramadol produced significant antidepressant effect at all the three (10, 20, and 40 mg/kg) doses, as indicated by reduction in immobility times of drug-treated mice compared to control mice. The efficacy of tramadol at doses of 10 and 20 mg/kg was comparable to that of fluoxetine, but antidepressant activity in animals administered with tramadol 40 mg/kg was significantly less as compared to fluoxetine-pretreated mice. Conclusion: The results of the present study indicate antidepressant-like activity of tramadol.

Evaluation of antidepressant activity of tramadol in mice

Objective: To evaluate antidepressant like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10,20 and 40 mg/kg, i.p) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug treated mice were recorded in tail suspension test (TST).The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p), administered for seven days. Results: Tramadol produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control. The efficacy of tramadol at doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10 mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. Conclusion: The results of the present study indicate antidepressant like activity of tramadol.

Effect of Celecoxib on Anticonvulsant Activity of Carbamazepine against Maximal Electroshock-Induced Convulsions in Mice

This study investigates the effect of celecoxib alone and in combination with carbamazepine (CBZ) on maximal electroshock-induced convulsions in mice. Celecoxib (30, 45, 60, 75 and 90 mg/kg) and CBZ (2, 4, 6 and 8 mg/kg) were each given alone in increasing doses, and CBZ was given in combination with a single dose of celecoxib (30 mg/kg) 40 min prior to electroshock-induced convulsions. The percentage protection and duration of hind limb extension were determined using an electroconvulsiometer. The ED50 value (dose at which there is protection in 50% of animals) of CBZ alone and in combination with celecoxib was determined. When administered alone, CBZ showed an increase in percentage protection at increasing doses, with 100% protection occurring at a dose of 8 mg/kg. However, treatment with celecoxib alone demonstrated maximum protection of 50% occurring at the 60 mg/kg dose. Moreover, celecoxib given at 30 mg/kg did not show any protection. Nevertheless, coadministration of celecoxib (30 mg/kg) enhanced the effect of the subprotective dose of CBZ and was more effective than CBZ given alone. Combined treatment with celecoxib enhanced the potency of CBZ and significantly reduced its ED50 value. This study suggests that celecoxib has an anticonvulsant effect of its own and it also potentiates the anticonvulsant efficacy of CBZ against maximal electroshock-induced convulsions in mice.

Adverse drug reactions and their impact on quality of life in patients on antipsychotic therapy at a tertiary care center in Delhi

Context: Adverse drug reactions (ADR) due to antipsychotic therapy have significant impact on a psychiatric patients quality of life. Few studies have been conducted in India to monitor adverse drug reactions due to antispsychotics and none has been done to determine their impact on quality of life. Aims: The present study was conducted to monitor ADRs due to antipsychotics and ascertain the impact of ADRs on quality of life. Settings and Design: This prospective observational study was conducted in the psychiatry outpatients department in New Delhi for 1 year. Patients and Methods: A total of 224 patients enrolled were followed up for a period of 3 months. ADRs were monitored using the standard form of the Central Drugs Standard Control Organization and causality was determined using the Naranjo algorithm. The WHO Quality of Life BREF (WHOQOL-BREF) scale was used to study the effect of ADR on the quality of life. Statistical Analysis Used: The data were entered and analyzed using the statistical software SPSS 17.0. Unpaired t-test was used to compare the quality of life of patients who encountered ADRs and those who did not. P < 0.05 was considered statistically significant. Results: Of the total 224 patients, 38 adverse drug events occurred. Adverse drug events were mostly with risperidone (10), followed by olanzapine (8) owing to high usage. Majority of the events were classified as probable (34). The occurrence of adverse drug events decreased the scores on physical and psychological domain scores of WHO-QOL BREF at 3 months compared to baseline. Conclusions: The study provides information on the existing incidence of ADRs in the setup with an established pharmacovigilance center. The nature of ADRs correlates with the prevalence pattern of usage of atypical antipsychotics. Clinicians need to weigh benefit versus the impact on quality of life while prescribing antipsychotics.

Orphan drugs: trends and issues in drug development

Abstract Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach

Screening of antimalarial drugs: An overview

178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.