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Essential Medicine Concept, a major breakthrough in health care, started in 1977 when World Health Organization (WHO) published its first list. Appropriate use of essential medicines is one of the most cost-effective components of modern health care. The selection process has evolved from expert evaluation to evidence-based selection. The first Indian list was published in 1996 and the recent revision with 348 medicines was published in 2011 after 8 years. Health expenditure is less in India as compared to developed countries. India faces a major challenge in providing access to medicines for its 1.2 billion people by focusing on providing essential medicines. In the future, countries will face challenges in selecting high-cost medicines for oncology, orphan diseases and other conditions. There is a need to develop strategies to improve affordable access to essential medicines under the current health care reform.

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Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib.

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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 HbA _1c . 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.

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Injection is one of the important health care procedures used globally to administer drugs. Its unsafe use can transmit various blood borne pathogens. This article aims to review the history and status of injection practices, its importance, interventions and the challenges for safe injection practice in developing countries. The history of injections started with the discovery of syringe in the early nineteenth century. Safe injection practice in developed countries was initiated in the early twentieth century but has not received adequate attention in developing countries. The establishment of "Safe Injection Global Network (SIGN)" was an milestone towards safe injection practice globally. In developing countries, people perceive injection as a powerful healing tool and do not hesitate to pay more for injections. Unsafe disposal and reuse of contaminated syringe is common. Ensuring safe injection practice is one of the greatest challenges for healthcare system in developing countries. To address the problem, interventions with active involvement of a number of stakeholders is essential. A combination of educational, managerial and regulatory strategies is found to be effective and economically viable. Rational and safe use of injections can save many lives but unsafe practice threatens life. Safe injection practice is crucial in developing countries. Evidence based interventions, with honest commitment and participation from the service provider, recipient and community with aid of policy makers are required to ensure safe injection practice.

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Objective: To evaluate the clinical efficacy and safety of Tinospora cordifolia lotion including its cure rate and clearance time compared with permethrin lotion . Materials and Methods: A single blind, randomized, controlled, pilot clinical study was performed in three government institutions to investigate clinical efficacy of T.cordifolia lotion in sixty-six clinically-diagnosed scabies-infected patients. The patients were treated with T.cordifolia or permethrin lotions for three consecutive days for two weeks and clinical assessment of each patient was performed for five weeks. Results: T. cordifolia lotion and permethrin significantly reduced the mean global evaluation score after four weeks of treatment. The two lotions showed comparable effects as anti-scabies agent. Moreover, the clearance time (days) and cure rate using the two lotions did not differ. Clinical improvement, mean clearance time and cure rate of T.cordifolia lotion are comparable with permethrin . Conclusions: Tinospora cordifolia lotion exhibits anti-scabies activity comparable with permethrin. Its incorporation as therapeutic reagent in Sarcoptes scabiei infections is highly recommended.

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Introduction: To compare the efficacy and tolerability of Ivabradine (IVA) and Ranolazine (RAN) in chronic angina patients. Materials and Methods: This was a follow-on, open-label trial conducted in a tertiary care hospital of Uttarakhand. Thirty patients each taking IVA 5 mg twice daily or RAN 500 mg twice daily were distributed to the respective groups. Patients were asked to fill a pretested questionnaire on frequency of anginal attacks and adverse reactions before and 2, 4 and 8 weeks after taking the respective medicines. Their blood pressure, heart rate and routine hematological and biochemical estimations were performed at baseline and after intervention. Results were statistically analyzed using different statistical tests, with P < 0.05 considered as significant. Results: There was no significant difference in the frequency of anginal attacks per week between the groups. The adverse drug reactions (ADRs) reported in the IVA group were dizziness (30%), headache (16.6%), backache (16.6%), vertigo (13.3%), blurred vision (13.3%), muscle cramps (10%), arthralgia (10%), cough and dyspnea (6.6%), hypersensitivity rash (6.6%), fever (3.3%) and nausea (3.3%). The ADRs in the RAN group were nausea (26.6%), dizziness (23.3%), vomiting (3.3%), constipation (3.3%) and vertigo (3.3%). The blood pressure, heart rate and routine hematological and biochemical evaluations did not show any significant difference in the pre-post values. IVA significantly decreased the resting heart rate after eight weeks of intervention. Conclusions: Both antianginal agents appeared equiactive. However, RAN had a better safety and tolerability profile than IVA. Serum sickness-like reaction was an adverse event noticed with IVA, which needs causality establishment.

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Objective: To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats. Materials and Methods: Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM). Result: As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy. Conclusion: These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity.

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The purpose of this paper is to report a rare occurrence of Stevens-Johnson/Toxic epidermal necrolysis (SJS/TEN) overlap syndrome after the use of aceclofenac. A 38 year old healthy adult male presented with rapidly evolving rash over face and upper body with ulceration of buccal mucosa and breathlessness after taking aceclofenac tablet. Naranjo score for this adverse drug event was six, thereby making it a probable adverse drug reaction. Despite aggressive fluid resuscitation and use of antihistamines and systemic steroids, patient's health rapidly worsened and died within six hours of presentation. Aceclofenac induced SJS/TEN overlap is an extremely rare clinical association previously reported only once in medical literature. To the best of our knowledge, this is the first case report of such an association in the Indian population. We are presenting this case to highlight the serious adverse reactions possible from a routinely prescribed drug.

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Objective: To study the genetic variation and haplotype structure of Vitamin K epoxide reductase complex, subunit 1 (VKORC1) gene in the Tamilian population. Materials And Methods: The study was performed on 210 unrelated, healthy volunteers of the Tamilian population, of either sex between the age group of 18-60 years. Five ml of venous blood sample was collected using sodium ethylene diamine tetra acetic acid (EDTA) as anticoagulant. DNA was extracted using phenol-chloroform extraction method. Eight single nucleotide polymorphisms (SNPs) VKORC1 rs9923231 (G), rs7196161 (T), rs2884737 (T), rs17708472 (C), rs9934438 (C), rs8050894 (G), rs23596121 (C), and rs7294 (A) were studied using real-time quantitative Polymerase Chain Reaction (qPCR) method and they were included for constructing five-major haplotype blocks of VKORC1 gene. Results: The major alleles of VKORC1 rs9923231 (G), rs7196161 (T), rs2884737 (T), rs17708472 (C), rs9934438 (C), rs8050894 (G), and rs23596121 (C), were found to be at frequencies of 90.0%, 89.2%, 90.9%, 94.1%, 90.7%, 89.5% and 91.2%, respectively. The variant allele of VKORC1 rs7294 (A) was more frequent (83.6%) in the Tamilian population. The frequencies of haplotypes HAP1 (GTTCCGCA), HAP2 (ACGCTCTG), HAP3 (GTTTCGCG), HAP4 (GTTCCGCG) and HAP5 (GCTCCCCG) were found to be 80.0%, 7.4%, 4.7%, 1.5% and 1.1%, respectively. Conclusion: In the present study the allele- frequency distributions, genotype and haplotype frequencies of the VKORC1 gene was considered. The findings of this study provide the genetic information required for learning the association of VKORC1 genetic variation and oral anticoagulant dose variability among patients receiving oral anticoagulants in the Tamilian population.

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Objective: To determine the effect of Casilan^® on ¹³ C-caffeine metabolism in healthy Nigerian children. Materials and Methods: Twelve healthy Nigerian children (male: six, female: six) aged 3-8 years were studied on three occasions. After an overnight fast, the children were studied after ingesting Casilan^® only (Week 1). They were restudied after ingesting 3 mg/kg of labeled caffeine only (Week 2), and further re-studied after ingesting both Casilan^® and labeled caffeine (Week 3). Breath samples were collected by blowing via a straw into an exentainer bottle. The cumulative percentage of ¹³ C-caffeine exhaled as ¹³ CO ₂ was measured over 2 h. Results: The time courses of ¹³ C-enrichments in exhaled CO ₂ for all the children, after they had ingested labeled caffeine only and after they had ingested both Casilan^® and labeled caffeine, were identical. There was a gradual rise and peak of the enrichments at about 60-75 min, followed by a gradual fall (II) or a plateau (III). Contrarily, the time course of ¹³ C-enrichments for all the children was consistently low and stable after they had ingested Casilan^® only (I). The mean values of cumulative percent ¹³ C-doses recovered in the CO ₂ exhaled over a 2-h period, after ingesting labeled caffeine only (8.59 ± 1.10 δ%/mg) and after ingesting both Casilan^® and labeled caffeine (8.58 ± 1.33 δ%/mg), were identical, with no statistically significant difference (P = 0.972). This suggests that Casilan^® did not affect the CYP1A2 metabolic pathway. Conclusions: Casilan^® is a safe, reliable and quantitative food supplement for overnight-fasted children undergoing caffeine breath test.

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We present an unusual case of 24 year old male who was hospitalized for dental procedure and developed cardiac arrest 2 days after the procedure. The patient presented with swelling of buccal cavity for which a biopsy was taken. Two days after the procedure, apparently normal patient suddenly presented at mid night with VT and VF, which were intractable requiring multiple DC shocks. During this period arterial blood gas analysis revealed severe acidosis. The circumstances led us to suspect poisoning as one of the cause for his medical condition. We looked for commonly available toxins. One of the commonly available toxins is hand sanitizer which contains Isopropyl alcohol, glycerin and perfume. Due to prolonged cardiac arrest and intractable arrhythmia patient had sustained hypoxic brain injury. Patient remained hemodynamically stable for next 9 days although his CNS status did not improve. Patient succumbed to sepsis on 9 ^th day. Healthcare professionals should be aware of such possibilities and treat the patients at the earliest and put a check on the easy availability of IPA based hand sanitizers.

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