Effect of garlic oil on ethanol induced gastric ulcers in rats.

Garlic oil was evaluated for gastroprotective activity against ethanol induced ulcers. Reactive oxygen species are involved in the pathogenesis of these ulcers. The possible involvement of garlic oil in restraining the oxidation process produced in gastric tissue was also investigated. The ulcer index, lipid peroxidation and antioxidant enzyme activity (GPx, catalase, SOD) were determined. Pretreatment with garlic oil in doses of 0.25 and 0.5 mg/kg, 30 min before administration of ethanol (1 mL of 100%) caused a decrease in ulcer index and lipid peroxidation and ameliorated the decrease in antioxidant enzyme levels caused by ethanol. The result suggests that garlic oil possesses antioxidant properties and provides protection against ethanol induced gastric injury.

Open labeled, randomized, switch-over study of two fixed doses (10/15mg) of aripiprazole : to evaluate its safety and efficacy in the treatment of Indian patients of schizophrenia.

Aripiprazole is a new anti psychotic with a unique receptor binding profile that combines partial agonistic activity at D2 receptor and 5-HT 1A receptor and potent antagonism at 5-HT 2A receptor. This receptor profile makes it possible for it to act as a dopamine system stabilizer. Based on various short term and long term studies, aripiprazole has been found to be effective in schizophrenia and has no significant adverse effect on QTc prolongation, prolactin, serum lipids, and has a low potential for weight gain. Present study aims to evaluate the efficacy and tolerability of aripiprazole (10-15mg/day) in the treatment of Indian patients of schizophrenia and to see its effect on QTc interval, prolactin levels, serum lipids, plasma sugar and weight gain in these patients. Outpatients with an ongoing/newly diagnosed ICD-10 Schizophrenia (n=136) were randomly assigned to 10 or 15 mg dose of Aripiprazole for a period of six weeks. Clinical response was evaluated by the Positive And Negative Symptoms Scale (PANSS), Clinical Global Impression (CGI) scale and safety was evaluated by observing spontaneously reported adverse events and changes in various laboratory parameters. Switching schizophrenic patients to aripiprazole (10/15 mg) from both conventional and atypical anti-psychotics was safe and well tolerated. Six weeks after switching to aripiprazole, patients showed improvements in PANSS scores (P< 0.001), EPS, prolactin levels and weight over the baseline levels. No difference was seen in the 10 or 15mg dose groups. One hospitalization was reported (due to hepatitis E). Common side effects reported were insomnia, somnolence, nausea, vomiting and diarrhea. Aripiprazole is a safe and effective anti psychotic in Indian patients - both in newly diagnosed, as well as, in patients not responding to or intolerant to other available typical and atypical antipsychotics.

The drug lag: new drug introductions in India in comparison to United States.

CONTEXT: Important drugs become available late in India, some much later, than in the United States. The prevailing trends in new drug introduction in India as compared to USA have been looked into this study. OBJECTIVES: To determine the trends in new drug introduction, both qualitative and quantitative, during the period, 1988 to 1999, in India. DESIGN: Data search, compilation and analysis. SOURCE: Various issues (1982-1997) of "Journal of the American Pharmaceutical Association" and "Indian Drug Manufacturers Association" Bulletin (1988-2000). MAIN OUTCOME MEASURES: Average drug lag, trends in drug lag over years (1988-1999), drug lag by therapeutic categories, drug lag by FDA classification of drugs. RESULTS: Average drug lag in India during the years 1988 to 1999 was 4.02 +/- 2.77 years. It has shown a decreasing trend over the years. Gastrointestinal drugs have the least drug lag (1.2 +/- 2 years). Cardiovascular drugs suffer the highest drug lag among therapeutic categories (5.21 +/- 2.2 years). 1AA drugs and 1P drugs (FDA classification) are priority drugs in India also. 1A drugs, which are important new therapeutics agents have been unfortunately neglected by drug developers and regulatory authorities in India. CONCLUSION: Important new drugs become available in India with a drug lag. This 'drug lag' has declined over the years. Qualitative analysis show that 1A class drugs, supposedly the most important category, has been the worst affected.

A comparison of non-tapering vs. tapering prednisolone in acute exacerbation of asthma involving use of the low-dose ACTH test.

OBJECTIVE: To determine if there is a difference in early relapse rates and adrenal suppression between patients receiving an 8-day course of 40 mg/day prednisolone and those receiving an 8-day tapering course of prednisolone. METHODS: This was a prospective, randomized, open clinical trial conducted in a tertiary care center. All asthmatic patients with exacerbation who were judged well enough for discharge home from the emergency department were eligible for participation. Patients with a history of chronic obstructive pulmonary disease, congestive heart failure, pneumonia, pneumothorax, or other pulmonary process and asthmatics already using inhaled or oral steroids within 2 weeks of admission to the emergency department were excluded. Patients on discharge were administered either on 8-day course of 40 mg/day prednisolone or an 8-day tapering course of prednisolone (tapering from 40 mg to 0 mg). Patients were asked to return on Day 12 for cosyntropin stimulated test and pulmonary function testing and on Day 21 for pulmonary function testing only. RESULTS: A group of 13 patients treated with non-tapering course (40 mg/day) of prednisolone for 8 days were compared to a group of 13 patients treated with a tapering course (40 mg taper by 5 mg/day) for 8 days. There were no differences in the FEV1 percent predicted (Days 12 and 21), the incidence of relapse, or the incidence of adrenal suppression between the 2 groups. CONCLUSION: In this small study, we found no significant difference in relapse rate or adrenal suppression between asthmatics receiving an 8-day tapering dose of prednisolone and those receiving 40 mg/day prednisolone upon discharge from the emergency department.

Pattern of use and pharmacoeconomic impact of antihypertensive drugs in a north Indian referral hospital.

OBJECTIVE: The current study was designed to investigate drug utilisation and the pharmacoeconomics of hypertension in the hypertension clinic of a tertiary-care hospital. METHODS: The study was conducted in patients attending the hypertension clinic of Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, India. A survey of prescriptions was carried out, and the information obtained was further corroborated by seeing the medical records as well as patient interviews. RESULTS: A total of 1,076 prescriptions were evaluated. Beta-adrenoceptor-blocking agents (51%), calcium antagonists (47%) and angiotensin-converting enzyme inhibitors (46%) were the most popular drugs. The utilisation of thiazides was less than expected. Combination therapy was used more commonly than monotherapy (53.8% vs 46.7%). Oral hypoglycaemic agents and lipid-lowering agents were commonly co-prescribed along with antihypertensive medications. About 30% of drugs were prescribed by generic name and 90% were from the national essential drugs list. Of the per capita income, 10.6% was spent on the treatment of hypertension. The mean monthly cost of various drugs ranged between US $0.8 and US $6.6. A total of 91 adverse drug reaction (ADRs) were encountered in the study; the added cost of treatment of these ADRs was US $211. CONCLUSION: In general, the treatment guidelines for hypertension were followed in our hospital. The utilisation of thiazides was an area requiring improvement. The cost of treatment of hypertension was substantial and imparted a significant economic burden on the patients.

Drug related medical emergencies in the elderly: role of adverse drug reactions and non-compliance.

BACKGROUND: Adverse drug reactions and non-compliance are important causes of admissions in the elderly to medical clinics. The contribution of adverse drug reactions and non-compliance to admission by the medical emergency department was analysed. METHODS: A total of 578 consecutive elderly patients admitted to the medical emergency department were interviewed to determine the percentage of admissions due to adverse drug reactions or non-compliance with medication regimens, their causes, consequences, and predictors. RESULTS: Eighty three (14.4%) of the 578 admissions were drug related: 39 (6.7%) caused by adverse drug reactions and 44 (7.6%) caused by non-compliance with medication. One hundred ninety two (33.2%) patients had a history of non-compliance. Factors associated with an increased risk of admission because of an adverse drug reaction were patients with diabetes or neoplasms, and patients using numerous different medications. Factors associated with a higher risk of hospitalisation because of non-compliance were poor recall of the medication regimen, seeing numerous physicians, female sex, polypharmacy, drug costs, and switching over to non-conventional forms of treatment. CONCLUSION: Many elderly admissions are drug related, with non-compliance accounting for a substantial fraction of these. Elderly people at high risk of suffering a drug related medical emergency are identified and suitable interventions may be planned by the healthcare policymakers to target them.

A meta-analysis of controlled clinical trials comparing low-molecular weight heparins with unfractionated heparin in unstable angina.

BACKGROUND: Unfractionated heparin has been used extensively for the treatment of unstable angina/non-Q wave myocardial infarction but it has several disadvantages. Low-molecular weight heparins are now recommended although they are 3-5 times costlier than unfractionated heparin since they are convinient to administer and do not require activated thromboplastin time monitoring. Whereas enoxaparin, a low-molecular weight heparin, has been demonstrated to be superior to unfractionated heparin, the results of other low-molecular weight heparins have not been so convincing. METHOD AND RESULTS: Through manual, MEDLINE and EMBASE search, we identified five randomized trials (excluding enoxaparin trials) that compared low-molecular weight heparins with unfractionated heparin in unstable angina. The prespecified efficacy end point of interest included a composite of death, myocardial infarction, recurrent angina and urgent revascularization. The safety end point was taken as a composite of major hemorrhage, minor hemorrhage, thrombocytopenia, allergic reaction and any other adverse event. We calculated odds ratio (95% confidence interval) for each trial for the composite end point, and the pooled odds ratio (95%) confidence interval) was calculated using two established methods of meta-analysis, the Mantel-Haenszel-Peto method and the DerSirmonian-Laird method. Both the methods yielded similar odds ratio (95% confidence interval). Separate odds ratio were calculated for efficacy and safety end points. There was a nonsignificant reduction in the incidence of the composite efficacy end point: the odds ratio (95% confidence interval) was 0.83 (0.70-0.99: p=0.08). The odds ratio (95% confidence interval) for the safety data was 0.78 (0.69-1.26: p=0.33). CONCLUSIONS: No statistically significant difference was observed when the efficacy and safety of low-molecular weight heparins were compared with those of unfractionated heparin. A cost-effectiveness analysis of low-molecular weight heparins versus unfractionated heparin must be done urgently to establish more firmly the place of low-molecular weight heparins in the management of unstable angina.

Effect of acute and chronic administration of L-arginine on morphine induced inhibition of gastrointestinal motility.

Effect of acute and chronic administration of L-arginine on morphine induced gastrointestinal inhibition was tested in rats. In the test for acute effect, L-arginine (200 mg/kg, i.v.) was given 10 minutes before the charcoal meal test. In the test for chronic effects, L-arginine (200 mg/kg, i.v.) was given twice a day for 4 days. Charcoal meal test was done on the fifth day. Morphine was administered 45 minutes before the charcoal meal test. Results showed that acute administration of L-arginine did not affect the morphine's action on the GIT. In contrast, chronic administration of L-arginine reversed the morphine induced decrease in gastrointestinal motility. The reversal was however, not complete. This data suggests that inhibition of NO may be one of the mechanism of morphine induced constipation.

Effect of the 5-HT3 receptor antagonist ondansetron on amphetamine-induced hyperactivity and stereotypy in rats.

The effects of different doses of ondansetron (0.1, 0.5, 1, 2 mg/kg) administered intra-peritoneally were studied on amphetamine-induced hyperactivity and stereotypy in wistar rats. Ondansetron was administered 30 minutes prior to d-amphetamine (3 mg/kg, i.p.). Ondansetron in doses of 0.5 and 1 mg/kg significantly decreased the mean number of head dippings and crossings in the hole board test and in doses of 0.1 and 0.5 mg/kg significantly decreased the average stereotypic score. Since the hyperactivity and stereotypy are dopamine mediated, the effect of ondansetron to reduce these states suggests a potential role for ondansetron in conditions with dopamine excess.

Effect of muscarinic receptor agonists on animal models of psychosis.

The purpose of this study was to determine the effects of muscarinic receptor agonists on models of psychosis in rats. A battery of three tests, catalepsy (haloperidol-induced) augmentation, amphetamine-induced stereotypy antagonism and conditioned avoidance response were used. Both muscarinic receptor agonists physostigmine and pilocarpine produced similar results. They dose-dependently augmented the haloperidol-induced catalepsy, inhibited amphetamine-induced stereotypy behavior and inhibited the conditioned avoidance response. Results demonstrate that muscarinic receptor agonists have actions similar to those of dopamine receptor antipsychotic drugs in animal models, suggesting that muscarinic receptor agonists may be used as adjuvant drugs in the treatment of psychosis.

Effect of trikatu, an Ayurvedic prescription, on the pharmacokinetic profile of rifampicin in rabbits.

The effect of single and multiple doses of a herbal preparation trikatu, an Ayurvedic prescription, on the bioavailability and pharmacokinetics of rifampicin was studied in rabbits. Rabbits (n = 10) were administered a single dose of rifampicin (24 mg/kg, p.o.) alone or in combination with a single dose of trikatu (500 mg/kg, p.o.). The study had a cross over design with a washout period of 7 days. In the other study, six rabbits were administered a single dose of rifampicin (24 mg/kg, p.o.) before and after multiple doses of trikatu (500 mg/kg x 7d, p.o.). In both studies, blood samples were collected at 0, 0.5, 1, 1.5, 2, 4, 6, 9 and 12 h after drug administration and assayed for rifampicin. In animals treated with single dose of trikatu there was a significant decrease in the peak plasma concentration (Cmax) of rifampicin (P < 0.05). Multiple doses of trikatu also reduced the Cmax and delayed the Tmax of rifampicin although not to a statistically significant level. Other pharmacokinetic parameters of rifampicin were not significantly altered. Our results suggest that coadministration of trikatu does not influence the extent of bioavailability (AUC0-infinity) but reduces the rate of bioavailability (Cmax) of rifampicin. And this latter effect may reduce the efficacy of rifampicin therapy.

EFFECT OF 5-HT3 ANTAGONIST ONDANSETRON ON WRAP-RESTRAINT AND CONDITIONED EMOTIONAL STRESS INDUCED DEFECATION.

The effect of ondansetron was investigated in wrap-restraint and conditioned emotional (footshock) stress induced colonic hypermotility in rat. Ondansetron was administered in doses of 0.1, 0.5 and 1 mg/kg, sc. In wrap-restraint group, ondansetron dose-dependently reduced the fecal output to baseline levels (0.51 ± 0.20 gm/rat, 0.48 ± 0.38 gm/rat, 0.38 ± 0.16 gm/rat with 0.1, 0.5 and 1 mg/kg respectively). Diazepam, 5 mg/kg and atropine, 1 mg/kg also decreased the fecal output in this model. In footshock group, ordansetron did not affect the emotional stress induced increase in fecal pellet output. Diazepam and atropine however, decreased the fecal output in this model also.

EFFECT OF TRIKATU, AN AYURVEDIC PRESCRIPTION ON THE PHARMACOKINETIC PROFILE OF CARBAMAZEPINE IN RABBITS.

The effect of single and multiple doses of a herbal preparation Trikatu was studied on the bioavailability and pharmacokinetics of carbamazepine in rabbits. Rabbits (n = 10) were administered a single dose of carbamazepine (80 mg/kg; p.o.) and after a washout period of 7 days in combination with a single dose of Trikatu (500 mg/kg; p.o.). In the other study, six rabbits were administered a single dose of carbamazepine (80 mg/kg; po.) before and after multiple doses of Trikatu (500 mg/kg x 7d; p.o.). The blood samples were collected at 0, 1, 2, 4, 6, 9, 12 and 24 hours after drug administration and assayed for carbamazepine. In the animals treated with single dose of Trikatu, there was a significant decrease in T(max) of carbamazepine (P < 0.05). Multiple doses of Trikatu also shortened the T(max) of carbamazepine although not to statistically significant level. Our results suggest that the steeper rise and fall in the plasma levels of carbamazepine brought about by Trikatu, do not constitute significant advantage.