Santanu Kumar Tripathi

Clinico-epidemiological characteristics of patients presenting with organophosphorus poisoning.

Background: Organophosphorus (OP) poisoning is a major health problem all over the world, particularly in the developing countries. Aim: The present study aims to explore the clinical and epidemiological features found in patients presenting with OP poisoning. Materials and Methods: A 1-year cross-sectional study was conducted on patients presenting with clinical features of OP poisoning in a tertiary care medical college. Results: A total of 968 patients presented during the study period. Poisoning with suicidal intent (82.02%) was more common than the accidental one (17.98%). Majority of the patients were housewives (42%) followed by farmers, shopkeepers, laborers, students. Methyl parathion was the most common poison consumed by the patients (35.74%) followed by diazinon, chlorpyriphos, dimicron. Nausea and vomiting (85.02%) was the most common symptom while miosis was the most common sign observed in 91.94% patients. A total of 56 patients of OP poisoning died (5.78%) with respiratory failure being the primary cause of death followed by CNS depression, cardiac arrest, and septicaemia. Conclusion: The present study showed that majority of the patients were of young age with females outnumbering males. Poisoning with suicidal intent was more common than accidental. Nausea and vomiting was the most common symptom reported by the patients while miosis was the most common sign observed by the treating physicians of the research team.

Pesticide use pattern among farmers in a rural district of West Bengal, India.

Background: A vast majority of Indian population are engaged in agriculture. While pesticides help in increasing crop production, inappropriate pesticide storage practice and inadequate protective measures frequently causes accidental poisoning among farmers. Objective: The present study was conducted to explore the pattern of pesticide use among farmers in a district of India with an attempt to identify the lacunae in their knowledge and awareness level on risks and hazards of pesticides use. Materials and Methods: A cross-sectional questionnaire based study was conducted in the district of Burdwan, West Bengal, to address the study objective. Data analysis was performed by using descriptive statistical methods: Frequency, percentage, mean, standard deviation. Results: In the present study alpha-cypermethrin (46%) was the most commonly used pesticide followed by methyl parathion (25.6%), imidacloprid (16.4%), dichlorvos (7.8%) and phorate (4.2%). The farmers used to store pesticides mostly in cowshed (48.4%) followed by storeroom (29.6%). During spraying of pesticides, farmers experienced headache (29.8%) followed by nausea (26%), burning sensation in eyes (9.8%), cough (9.2%), muscle cramps (2%). Regarding the personal protective measures taken by the farmers for spraying, covering nose, mouth with cloth combined with bath after spraying was the most common practice (27%). When asked about suggested actions to be taken if anybody becomes sick following exposure to pesticides, 86% of farmers prefer consulting a doctor. Conclusion: The study suggested that farmers of Burdwan were exposed to highly hazardous, restricted and banned pesticides, with insufficient protection. In this situation, educational and training interventions on pesticide handling and safety precautions are urgently needed.

A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series

With the exception of fluoxetine, all selective serotonin reuptake inhibitors (SSRIs) commonly cause hyperprolactinemia through presynaptic mechanisms indirectly via 5-hydroxytryptamine (5-HT)-mediated inhibition of tuberoinfundibular dopaminergic neurons. However, there is little insight regarding the mechanisms by which fluoxetine causes hyperprolactinemia via the postsynaptic pathway. In this text, analysis of five spontaneously reported clinical cases of hyperprolactinemia resulting in overt symptoms of amenorrhea with or without galactorrhea, were scrupulously analyzed after meticulously correlating relevant literature and an attempt was made to explore the putative postsynaptic pathway of fluoxetine inducing hyperprolactinemia. Hypothetically, serotonin regulates prolactin release either by increasing oxytocin (OT) level via direct stimulation of vasoactitive intestinal protein (VIP) or indirectly through stimulation of GABAergic neurons. The pharmacodynamic exception and pharmacokinetic aspect of fluoxetine are highlighted to address the regulation of prolactin release via serotonergic pathway, either directly through stimulation of prolactin releasing factors (PRFs) VIP and OT via 5-HT2A receptors predominantly on PVN (neurosecretory magnocellular cell) or through induction of 5-HT1A-mediated direct and indirect GABAergic actions. Prospective molecular and pharmacogenetic studies are warranted to visualize how fluoxetine regulate neuroendocrine system and cause adverse consequences, which in turn may explore new ways of approach of drug development by targeting the respective metabolic pathways to mitigate these adverse impacts.

A Comparative Study of Lipid-Lowering Effects of Guggul and Atorvastatin Monotherapy in Comparison to Their Combination in High Cholesterol Diet-Induced Hyperlipidemia in Rabbits

ABSTRACT Background: Hypolipidemic activity of gugulipid has been widely described in traditional literature. Objective: This study was done to evaluate hypolipidemic activity of guggul and atorvaststin monotherapy in comparison to their combination in rabbits. Materials and Methods: Male New Zealand White rabbits (body weight 1.3–1.8 kg and age 8–10 weeks) were made hyperlipidemic by feeding cholesterol (0.5 g/kg) for three weeks and randomly divided into a control and three treatment groups receiving: atorvastatin (3.7 mg/kg), guggul (3.5 mg/kg) and their combination (same dose) for the next three weeks. Body weight measurements, estimation of serum lipid profile were done at the beginning, after three and six weeks, respectively. Histopathological examination of liver, heart and aorta was done after six weeks. Statistical analysis was done with SPSS version 16.0 using one-way and repeated measures analysis of variance (ANOVA) followed by post-hoc multiple comparison test with two tailed P value < 0.05 as significant. Results: All treated groups had significant reduction in cholesterol, triglyceride, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in comparison to pre-treatment values and control group, and had significant increase in high-density lipoprotein (HDL) in comparison to pre-treatment values. Conclusion: Combination of atorvastatin and guggul was comparable to their monotherapies in improving lipid profile.

Students' performance in written and viva-voce components of final summative pharmacology examination in MBBS curriculum: A critical insight

Sir, Assessment of learning has always been a difficult, yet an essential component of an educational program. In the undergraduate medical education system in India, curricular guidelines of Medical Council of India lay emphasis on methods of assessment of knowledge and skills in pharmacology.[1] Although continuous formative assessment constitutes an integral part in the curriculum, the ‘pass’ and the ‘fail’ certificates are based to a great extent on students’ performance in the final summative examination. The final examination consists of written papers, viva-voce sessions and practical exercises. Written examination consists of two papers. Each paper has the maximum marks of 40 and contains structured essay type questions and short notes. In viva-voce examination, each student is assessed by five examiners; two of them external examiners and the others internal examiners. In order to pass, a candidate must obtain 50% marks in aggregate with a minimum of 50% marks in written and viva together and a minimum of 50% marks in practical examination.[1] The written examination is a useful evaluation format that not only tests students’ ability to recall facts, but also can assess higher-order cognitive functions, such as interpretation of data and problem solving skills. The viva-voce examination on the other hand is a general encounter between a candidate and one or more examiners.[2] Viva-voce examinations are less reliable as they are essentially subjective in nature, afflicted with ‘halo effects’, errors of central tendency, a general tendency toward leniency, and errors of contrast.[2] Examiners mostly indulge in over-marking in viva-voce examinations in order to make an otherwise undeserving candidate ‘pass’. We explored this recently in a small questionnaire-based interview among examiners of pharmacology in one university and the examiners admitted showing such ‘leniency’. Against this backdrop, we planned the present study to compare students’ performance in written and viva-voce components of the final summative pharmacology examination in MBBS curriculum in order to have a critical insight into the two modes of evaluation, the way they are practiced. This was a record-based observational study done in a medical college in India that also served as an examination centre for second professional MBBS examination in pharmacology for four consecutive years, from 2008 to 2011. The performance of students was assessed. Permission for access to the students’ score sheets was obtained from appropriate authority and confidentiality of individual student’s score was maintained. Percentage of marks obtained by four batches of students (n=589), in consecutive years (2008-11), in written and viva-voce components of the final summative examination in pharmacology were reviewed: Batch 1 (Jan 2011 Exam, n=159), Batch 2 (Jan 2010 Exam, n=139), Batch 3 (Jan 2009 Exam, n=148), Batch 4 (Jan 2008 Exam, n=143). Based on their performance in terms of percentage of marks in aggregate, all students in a batch were classified into four categories viz., ‘failed’(F) – <50%, ‘borderline passed’ (BP) – 50-57%, ‘passed’ (P) – >57% to <75% and ‘passed with distinction’ (PD) – ≥75%. Correlation was assessed between the percentage of marks obtained by students in these categories in written vis-a-vis viva-voce examination. Highly significant association was observed in marks obtained by students in P and PD categories in all four batches in viva-voce and written examination (P<0.001). However, no significant association was observed in marks obtained by students in F and BP categories in all four batches in viva-voce and written examination (P>0.05). The results are shown in Table 1. Interestingly, no student in F category got 50% marks in written examination, but most of them scored satisfactorily in the viva-voce. Among all the students in F category, three students in 2008, five in 2009, four in 2010 and none in 2011 failed in practical examination. The number of students in each category (e.g., F, BP, P and PD) when compared among the 4 years (2008-11) did not show any significant difference [Figure 1]. Our study showed that there was highly significant association between written and viva-voce marks of students in the PD and P categories (P<0.001). We interpret this as the ‘true’ reflection of knowledge and competence of the students in this category. Our study also revealed that there was a lack of significant association in performance in written and viva-voce examination among students in F and BP categories (P>0.05). Marks obtained by students in viva-voce were higher with respect to those in written examination in these two categories. Rather, the poorer the performance in written examination, the higher the marks obtained in the viva-voce. Such trend is most prominent in the F category of students Access this article online

Effects of co-treatment with pioglitazone and methotrexate on experimentally induced rheumatoid arthritis in Wistar albino rats

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model. MATERIALS AND METHODS: Arthritis was induced by single subcutaneous injection of complete Freunds adjuvant (CFA) in thirty male Wistar albino rats. They were then divided into five equal groups, which included two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The disease-modifying action of the drugs was assessed by various physiological, hematological, and biochemical parameters along with histopathological and radiological analysis of affected joints. The experimental data were statistically assessed by one-way ANOVA. RESULTS: There was a significant reduction of disease activity in the MTX monotherapy group when compared with disease control. However, pioglitazone monotherapy group failed to demonstrate any significant effect on disease activity. The MTX-pioglitazone combination group demonstrated greater suppression of disease activity as compared to MTX and pioglitazone monotherapy and disease control group (P < 0.05). CONCLUSION: The present study demonstrates that the combination therapy of MTX with pioglitazone offers better control of disease activities in RA as compared to MTX or pioglitazone monotherapy.

Impact on behavioral changes due to chronic use of sertraline in Wistar albino rats.

Aim: Despite having better tolerability and a wide range of clinical applications over other antidepressants, selective serotonin reuptake inhibitors (SSRIs) are also known to be associated with serious adverse effects like suicidal ideation on chronic use. The present study had explored the impact of the chronic use of sertraline, an SSRI, on the behavioral changes in Wistar albino rats. Materials and Methods: The study was conducted on 30 Wistar albino rats of either sex; divided into five groups. Four groups were subjected to chronic mild stress induced by using various stressors randomly scheduled in a week and continued for a period of 3 weeks. The stressed rodents were subjected to sertraline treatment for 9 weeks in different human therapeutic doses extrapolated to animal doses. Behavioral changes were monitored, assessed, and evaluated throughout the treatment phase with the help of tests such as locomotor activity test, forced swim test, tail suspension test, antianxiety test, and sucrose preference test (SPT). Results: All tests except SPT, demonstrated significant (P < 0.05) reduction in depressive-like activity in the stressed rodents by the mid-treatment phase, followed by an abrupt onset of the depressive state by the end of the treatment phase. SPT showed a significant (P < 0.05) increase in sucrose consumption throughout the treatment phase. Conclusion: Behavioral changes following chronic sertraline administration conferred gradual remission of depression state on initial treatment phase, followed by a reversal of effect on chronic use.

Hepatotoxicity of atenolol therapy - A report of 2 cases

Abstract This case report highlights atenolol induced episodes of chronic and acute hepatotoxicities in 2 elderly hypertensive patients. The 1st patient manifested liver dysfunction after 8 months of 50 mg daily atenolol therapy and in the 2nd patient liver dysfunction was revealed within 3 weeks of 100 mg daily atenolol intake. There was no evidence of any other possible hereditary, traumatic, surgical, metabolic, infective, organic, or pathologic causes giving rise to these conditions. Possibilities of drug interactions were carefully ruled out and these episodes of hepatotoxicities were ‘probably’ drug (atenolol) induced, as depicted by CIOMS/RUCAM scale. Withdrawal of the offending drug resulted in reversal of the diseased states. Routine liver function tests may be warranted in patients on atenolol therapy.

A preliminary assessment of availability and pricing of children's medicines in government hospitals and private retail pharmacies in a district of Andhra Pradesh.

Sir, Children’s access to medicines in suitable pediatric formulations is a matter of global concern today.[1] Medicines prescribed for children are often off-label. Nonavailability of child size medicines encourages the use of adult dosage forms, splitting them into parts before giving to a child. This practice is not scientific and is far from rational, since children are not just miniature adults. Thus many children lack access to essential treatment because no suitable formulation exists, or those that do are either not available or are too expensive. In the backdrop of paucity of literature addressing this problem in India, this preliminary cross-sectional survey was planned to assess the availability and pricing of some common pediatric medicines in government health facilities vis-à-vis in private retail pharmacies. The study was conducted during May-June, 2011 in the district of East Godabari in Andhra Pradesh, India. The data collection form used for this purpose was developed with little modification of the ‘WHO Children’s Medicines Survey Form’,[2] customizing to suit our purpose. The availability and pricing of 20 core children’s medicines were assessed in the survey. All of these 20 core medicines were in ‘WHO Model List of Essential Medicines for Children, Oct 2007’,[3] and 15 of them were included in National Essential Medicine List of India 2003. [4] For data collection in this survey the WHO/HAI methodology was followed after due modification.[5] As no patient data were used in this survey, there was no ethical dilemma. However, permission was obtained from local health authority (from Chief Medical Officer of Health of the district) before conducting the survey. Two of the authors (LR and MB) acted as the data collectors, and visited the 8 public health facilities of different tiers, and 7 retail pharmacies, nearest to the respective public health facilities, during a period of 6 weeks in May-June, 2011. In retail pharmacies, the actual price to the patient of the cheapest brand as available on the day of the survey was documented. In public health facilities, procurement prices for medicines were obtained from State government’s Central Drug Stores (CDS) listing. For all practical purposes, formulations that existed in alternative pediatric dosage form and pack size were regarded as ‘available’. Overall, the availability was at best sub-optimal in all levels of public health facilities 35% in the teaching hospital pharmacy, 30% in the district hospital, 35% in primary health centers (PHCs) and 30% in community health centers (CHCs). Even availability in retail pharmacies was only 37.85% [Table 1]. Out of the 20 formulations, only six amoxicillin oral suspension, amoxicillin-clavulanate oral suspension, injection ceftiaxone, cotrimoxazole oral suspension, ORS sachet, paracetamol syrup were available in all the public facilities surveyed, as compared to only 5, e.g., amoxicillin oral suspension, injection ceftiaxone, ferrous salt suspension (combined with folic acid), ORS sachet, paracetamol syrup, in all private pharmacies. As high as 13 formulations (acyclovir suspension, artemether-lumefantrine tablet, beclomethasone inhaler, carbamazepine suspension, INH tablet, mebendazole chewable tablet, mebendazole syrup, nevirapine syrup, nystatin drops, rifampin-isoniazid tablet, salbutamol inhaler, vitamin A capsule, zinc dispersible tablet) i.e., 65% of the basket of medicines, were not available in any of the eight public facilities surveyed, while 10 out of the 20 core medicines, e.g., acyclovir suspension, artemetherlumefantrin tablet, beclomethasone inhaler, carbamazepine suspension, INH tablet, nevirapine syrup, nystatin drops, rifampin-isoniazid tablet, vitamin A capsule, zinc dispersible tablet, i.e., 50% were not available in any private pharmacy. The last named 10 medicines were not available in any government facilities either. Availability of anti-infectives was also poor in general. As many as 7 out of 12 (58.33%) antiinfective formulations in the WHO list of 20 core medicines were not available in either government hospitals or in retail pharmacies [Table 1]. The price comparison of medicines was done only for those items that were available in all or most of the government and private facilities. The cost of even the cheapest brand for a given medicine as available in a retail pharmacy was much higher than the procurement price of the same item for government facilities. Barring for one item, amoxicillin suspension, the variation of prices of medicines among different private facilities was not too wide. For amoxicillin suspension, the price range of the cheapest available products in different retail pharmacies was to the tune of Rs 80 – Rs 28 [Table 2]. Access this article online

Adverse drug reaction monitoring in patients on antiretroviral therapy in a tertiary care hospital in Eastern India

BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup. MATERIALS AND METHODS: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India. A total of 610 patients on various ART regimens were studied for suspected ADRs over 12 months. Adverse event history, medication history, and other relevant details were captured. Causality and severity of each reported ADR were duly assessed. RESULTS: 32.45% patients of total study participants presented with a total of 330 ADRs. Patients from zidovudine-based regimens presented with majority of ADRs such as anemia (up to 36%), central nervous system (CNS), and gastrointestinal (GI) side effects. Tenofovir-based regimens were, however, found to be mildly safer. The combination with Efavirenz was associated with majorly CNS side effects while that of nevirapine was associated with rash and pigmentation of nails. Atazanavir boosted second-line regimens were notably associated with increased serum lipid levels followed by other GI and CNS adverse effects. Increased liver enzymes were found in atazanavir-based second-line ART. CONCLUSION: The study enables to obtain information on the incidence and pattern of ADRs associated with various antiretroviral regimens, thereby reducing its occurrence and protecting the patient population from avoidable harm. Need of intensive monitoring for ADRs in ARTs thus seems to be a mandate.