Usha Gupta

Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats

BACKGROUND Non-steroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in clinical practice. Presently, several varieties of fixed dose combinations (FDCs) of NSAIDs are available over the counter and are being prescribed too. There is paucity of literature regarding comparative efficacy of these combinations against their individual component. Various clinical studies have documented increased incidence of gastric ulcerations with usage of more than one NSAID simultaneously. OBJECTIVES To study gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats. MATERIALS AND METHODS Gastric tolerability of different NSAIDs was observed after administration of drugs for 7 days orally. On 7 th day, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Analgesic or antinociceptive activity of single and combination NSAIDs was evaluated using Writhing test model. For induction of writhing, 4% normal saline (hypertonic saline) was injected (0.1 ml/10 gm) intraperitoneally. Evaluation of antiinflammatory activity for FDCs of NSAIDs was done by using rat paw edema model with the aid of plethysmometer. Paw edema was induced by injecting 0.1 ml of 1% formalin in sub-planter region of hind paw. RESULTS Analgesic activity was found to be enhanced or significant only in the group pretreated with combination of nimesulide with ibuprofen as compared to ibuprofen-alone group (P = 0.01). Decrease in mean paw edema (antiinflammatory activity) was not significant in rats pretreated with combination NSAIDs as compared to NSAID-alone group. Mean gastric ulcer index was significant in groups pretreated with diclofenac alone (P = 0.03) and in combination groups of nimesulide with diclofenac and ibuprofen with paracetamol as compared to control (P = 0.03, P = 0.007). CONCLUSION Addition of ibuprofen to paracetamol and combining diclofenac to nimesulide, significantly increased severity of gastric ulcerations. Fixed dose combination does not possess additional analgesic activity over their individual components, only exception being combination of nimesulide with ibuprofen, which has additional analgesic activity over ibuprofen alone, and this combination was not found to be ulcerogenic. Antiinflammatory activity of ibuprofen, paracetamol and nimesulide was significantly enhanced after addition of diclofenac.

Prescribing Behaviour of Physicians

To improve drug-use-related problems appropriately, demonstration of the inap propriate use of drugs alone is not sufficient. Data on its causation and suitable interventions are essential. Hence, a prospective randomised controlled study was conducted with the objective to identify drug-use-related problems in acute upper respiratory infections and non-specific acute diarrhoea with a special focus on use of antibiotics in 32 dispensaries and seven colony (15-bedded) hospitals in Delhi. An educational intervention in the form of small group discussions was introduced in the study group to improve the appropriate use of antibiotics. The control group did not participate in the small group discussions. The principal finding of the qualitative assessment was that the prescribers knowledge of anti biotic use and risks was generally sufficient, yet they overused antibiotics. The reasons or underlying factors encouraging the use of antibiotics in ARI and non- rehydration therapy (antidiarrhoeals, antibiotics, antiamoebics) and hindering the use of oral rehydration therapy in diarrhoea were worries regarding precise aetiology, to prevent secondary infections, the deterioration of the patients con dition, to meet the demand of patients and the fear of losing patients. The aver age number of drugs prescribed in ARI reduced significantly in both the groups (control group 2.82±0.88 vs. 2.63±0.58; study group 2.72±0.38 vs. 2.54±0.38) following intervention (p < 0.001). There was a significant reduction in the use of antibiotics in ARI in the study group from 64.86 to 51.30 per cent after inter vention (p < 0.003). There was no change (60.5 vs. 63.9 per cent) in the control group in ARI. In diarrhoea too the average number of drugs prescribed reduced significantly (p < 0.0001) in both the groups (study group 2.25±0.59 vs. 2.27±0.77; control group 2.31±1.76 vs. 2.76±0.73). Antibiotic use declined significantly in all health facilities in both the study groups (intervention group 82.1 per cent vs. 68.90 per cent; control group 80.3 vs. 62.3 per cent). In diarrhoea all the health facilities in the study group fell in the category of 50 to 80 per cent or more antibiotic use before intervention. About 75 per cent of the drugs were prescribed by generic names and more than 90 per cent were from the essential drugs list. The results of the study show that though antibiotic use declined after inter vention, there is a need for such interventions regularly to bring about long- lasting changes in prescribing behaviour.

Barriers and facilitators to development of standard treatment guidelines in India

This paper describes 15 years’ experience of the development process of the first set of comprehensive standard treatment guidelines (STGs) for India and their adoption or adaptation by various state governments. The aim is to shorten the learning curve for those embarking on a similar exercise, given the key role of high-quality STGs that are accepted by the clinical community in furthering universal health coverage. The main overall obstacles to STG development are: (i) weak understanding of the concept; (ii) lack of time, enthusiasm and availability of local expertise; and (iii) managing consensus between specialists and generalists. Major concerns to prescribers are: encroachment on professional autonomy, loss of treating the patient as an individual and applying the same standards at all levels of health care. Processes to address these challenges are described. At the policy level, major threats to successful completion and focused implementation are: frequent changes in governance, shifts in priorities and discontinuity. In the authors’ experience, compared with each state developing their own STGs afresh, adaptation of pre-existing valid guidelines after an active adaptation process involving local clinical leaders is not only simpler and quicker but also establishes local ownership and facilitates acceptance of a quality document. Executive orders and in-service sensitization programmes to introduce STGs further enhance their adoption in clinical practice.

Prescribing practices in private health facilities in Delhi (India).

Sir, The private health sector provides 80% of all out-patient care in India.[1] The main thrust of the Government’s drug policy has been on the manufacturing and marketing of medicines in the private sector and very little to the actual use of medicines, which are left to the market forces. The National Health policy 2002 (Government of India), has emphasized on the need for standard treatment regimens, in both public and private sector. The Government of Delhi also has a policy of use of only essential medicines. This however is applicable only in public health facilities. The present study was designed with the aim of assessing prescribing pattern and compliance of medicines prescribed and sold in the private health facilities with the essential medicines list (EML). A prospective, randomized, study using the methodology stated in the World Health Organization’s (WHO) manual on indicators for monitoring national drug policies was conducted.[2] The study was approved by the Institutional Ethics Committee. The sample frame was the city of Delhi. Its nine administrative districts were combined to give five zones north, south, east, west, and central. A total of 27 pharmacies were selected by multistage sampling. A minimum of 30 prescriptions each were collected from all pharmacies. They were analyzed using WHO’s basic drug (medicine) use indicators for health facilities and some indicators for evaluating national drug policies.[2,3] The indicators used were (i) average number of drugs per prescription (ii) percentage of prescriptions encounters with at least one injection (iii) percentage of prescriptions encounters with anti-microbials (the list of anti-microbials was defined before) (iv) percentage of drugs prescribed by generic names (v) percentage of drugs prescribed from the EML. In addition, (vi) percentage of tonics (vitamins, minerals, hematinics, enzymes, nutritional supplements) (vii) percentage of fixed dose drug combinations (FDCs) prescribed and (viii) percentage of complete prescriptions were also analyzed. A complete prescription was defined as one, where the name of the medicine, dose and frequency of administration and duration of therapy were all written by the prescriber. The prescribing of medicines from the EML was assessed by analyzing the sales of medicines in the private pharmacies in two ways. Country drug sales: The number of medicines being sold from the most recent National (2003) and Delhi State EML (2006), out of the 50 best-selling medicines in the market in India was analyzed for the years 2006, 2007, and 2008. There is a national EML and states may formulate their own EML based on local morbidity patterns and need. State medicine sales: To assess the use of medicines from the Delhi State EML, the percentage of medicines from the state EML sold, out of the total number of medicines sold was calculated. To calculate this indicator, the first 30 medicines sold in the private pharmacies were recorded. All brand or generic medicines sold with or without a prescription with dosage form were included. If the medicines contained one active ingredient, which is on the EML and other active constituents, which are not on the EML, they were not included. For combination medicines, only the ones from the EML were included. The number of prescriptions obtained was 823 with a total of 2164 medicines prescribed. Anti-microbials were the largest number of medicines prescribed (19.6%), followed by analgesics, anti-inflammatory, anti-pyretics (15.5%), and tonics (11.55%). The prescribing indicators are shown in Table 1. The number of medicines from the EML, among the top 50 selling medicines in the country ranged from 42% to 44% for national and 42% to 48% for Delhi State EML over 3 years. The percentage of medicines sold from the EML ranged from 27.64% to 39.24.2% in different zones in Delhi. Majority of prescriptions were incompletely written. This could be due to a basic lack of training in prescription writing or unawareness about the importance of writing a complete prescription. Prescribing of generics was very less. Brand names are reminded continuously to doctors by medical representatives of drug companies and other forms of drug advertising, whereas non-proprietary names are only taught in medical colleges. Prescribing generics offers economic advantages to patients. In most countries where use of generic medicines has been promoted it has primarily been through supportive legislation and regulations.[4] There appears to be excessive use of FDCs, which are not recommended, unless they are of proven efficacy and rationality. Although only a handful of essential FDC have been recognized by WHO, National (India) and Delhi State Access this article online

Ladakh. Is tetanus rare at high altitudes

1978, aimmg at a comprehensive health care delivery. Regional and district health management teams have been formed all over the country. Through various training courses, notably the strengthening of district health systems initiative, regional and district managers have been equipped with the skills to plan, implement and evaluate programmes to address health systems problems. Though there has been remarkable progress the results have been slow and difficult to sustain. Most of the initial problems stemmed from the verticalization of the Ministry of Health, overcentralization of functions and power, and conflict of interests. Most people are used to working along vertical lines and this hampers the building of horizontal relationships. With the current effort at re-structuring the ministry towards integration and decentralization, it is hoped that most of the bottlenecks towards the attainment of health goals shall be removed. Under such a restructured system it should be possible to accommodate both strategies under consideration. I believe that the basic strategy for

Improving Use of Medicines Implementation of an Essential Medicines Policy in Public Health Facilities in Delhi (India)

In 1994 the Government of Delhi (India) implemented an essential medicines policy in public health facilities (HF) to improve the availability and rational use of medicines (RUM). An essential medicines list (EML) was made. Training programmes in RUM were initiated. After 13 years the outcome of the policy on RUM within public HF was evaluated.  Policy implementation improved the availability of medicines to 91.4 per cent. Prescribing of medicines from EML increased (94.6 per cent) and antimicrobials declined (51.7 per cent). The number of patients with complete knowledge of how to take prescribed medicines improved (53.4 per cent). However, the use of generic medicines declined (18.1 per cent) and prescriptions were mostly incomplete (79.6 percent).  Majority of prescribers lacked awareness about the Drug Policy, including not having undergone training sessions on RUM. There were no Drugs and Therapeutic Committees within HF, and only a few doctors had information about medicines available within the HF. The most common sources of information for medicines were commercial published sources and medical representatives of pharmaceutical companies.  The regulatory intervention of enforcing an EML in public HF has been successful in increasing the use of medicines from the EML and improving some prescribing indicators. However, educational interventions have been inadequate and need to be combined and strengthened to improve the policy outcomes in RUM.