Efficacy and tolerability of trandolapril in mild to moderate hypertension--a double blind comparative clinical trial with enalapril in Indian population.

Several large scale clinical trials have demonstrated that angiotensin converting enzyme inhibitors offer cardiovascular and renal protection independent of their effects on systolic BP. Trandolapril is a new angiotensin converting enzyme inhibitor approved for the treatment of hypertension. The potential advantages of this drug are long duration of action and better tolerability. The objective of the study was to compare the efficacy and tolerability of trandolapril with that of enalapril in mild to moderate hypertension in Indian population. In this double blind, multicentric, parallel comparative clinical study, 120 patients with mild to moderate hypertension were randomly assigned to receive trandolapril 2 mg or enalapril 5 mg once daily for 8 weeks. The attainment of sitting diastolic blood pressure <90 mmHg at the end of 8th week was considered as primary outcome measure and attainment of diastolic blood pressure <90 mmHg or reduction of at least 10 mmHg diastolic blood pressure compared to baseline at any visit was considered as secondary outcome measures. 98.4% patients treated with trandolapril and 92.6% patients treated with enalapril fulfilled the primary outcome measure. 54, 72 and 62% patients on trandolapril and 52, 61 & 64% patients on enalapril fulfilled secondary outcome measure at the end of 2nd, 4th and 8th week respectively. Also trandolapril was better tolerated than enalapril with no significant abnormality in lab parameters.

Protective effect of Gingko biloba extract against doxorubicin-induced cardiotoxicity in mice.

Doxorubicin (DXR) causes dose dependent cardiotoxicity in experimental animals and in humans. In chronic doxorubicin cardiotoxicity model mice, the role of G. biloba extract (Gbe) which has an antioxidant property, was investigated. Doxorubicin treated animals showed higher mortality (68%), increased ascites, marked bradycardia, prolongation of ST and QT intervals and widening of QRS complex. Myocardial SOD and glutathione peroxidase activity were decreased and lipid peroxidation was increased. Ultrastructure of heart of DXR treated animals showed loss of myofibrils, swelling of mitochondria, vacuolization of mitochondria. G. biloba extract significantly protected the mice from cardiotoxic effects of doxorubicin as evidenced by lowered mortality, ascites, myocardial lipid peroxidation, normalization of antioxidant enzymes, reversal of ECG changes and minimal ultrastructural damage of the heart. The results indicate that administration of G. biloba extract protected mice from doxorubicin-induced cardiotoxicity.

Effect of pentoxifylline on cyclosporine-induced nephrotoxicity in rats.

Effect of unique hemorrheologic agent pentoxifylline (PTX) was investigated on cyclosporine (CsA) induced nephrotoxicity in rats. Compared to saline control, CsA produced significant increase in blood urea and serum creatinine. Pentoxifylline treatment prevented the CsA-induced rise in blood urea and serum creatinine. Creatinine clearance (Ccr) and lithium clearance (Licr) was decreased with CsA. PTX treatment prevented the CsA-induced decrease in Ccr and Licr. Malondialdehyde (MDA) was increased with CsA compared to saline treated animals. PTX prevented the CsA-induced MDA rise. Kidney form CsA treated rat showed marked vacuolar degeneration of tubular epithelium with excess of microcalcification. Severity of the lesions was markedly reduced in rats treated with PTX plus CsA. The results indicate that PTX reduces CsA-induced renal toxicity in rats.

Drug Utilization in Geriatric Population im a Tertiary.

One hundred and fi fty-two prescriptions of patients aged more than 65 years were picked up from in-patients of ollr hospital and analysed for drug utilization pattern. The mean age of the patients was 69.9 ±5.7 years. The mean number of drugs per prescription were 6.33 ± 2.35. Tablets were used in 48.5%, injections in 39.6%, capsules and syrups in 5.5% each and inhalers in 1.1% of patients. Antibiotics were prescribed for 140 patients, diuretics for 34, ACE inhibitors for 33, Calcium channel blockers for 59, H2 blockers for 84, narcotic analgesics and NSAlDs for 36 and 33 patients respectively. Beta blocker usage was minimal. Digoxin, aspirin and thrombolytics were used in 10, 50 and 5 patients respectively. Compliance was 100% and side effects Iike haemoptysis, gastritis, palpitation and vomiting were seen in I patient each.

Cardioprotective effect of magnesium chloride in experimental acute myocardial infarction.

Cardioprotective role of intravenous administration of magnesium chloride was evaluated in rabbits by biochemical and histopathological parameters. Myocardial damage was induced by injecting (i.v.) isoprenaline 1, 2.5, 5 and 7.5 mg/kg body weight of animal. There was a dose dependent increase in the activity of cardiac enzyme creatinine kinase CK (C Max). Maximal elevation of CK (C Max) was observed with 2.5 mg isoprenaline. The mean T-max (mean of the time duration in hr at which maximum creatinine kinase activity of individual rabbit was observed in a group) shifted early, significantly with 2.5, 5 and 7.5 mg isoprenaline compared to control group. Histopathologically, myocardial damage was quite significant in 2.5 mg isoprenaline subgroup of animals. A mortality of 29% was observed in animals injected with 5 and 7.5 mg isoprenaline, whereas all animals subjected with 1 and 2.5 mg isoprenaline were alive for 72 hr. Considering the data on serial determination of cardiac enzyme CK and histopathological changes, 2.5 mg isoprenaline was chosen as standard dose to study efficacy of cardioprotection by gold standard verapamil and magnesium chloride. Verapamil (5 microM) injected prior to 2.5 mg isoprenaline administration revealed significant reduction of CK (C Max) activity (P < 0.05) compared to animals infused with isoprenaline alone. T-max value did not show any alteration in both the groups. Histopathological findings showed no areas of necrosis and cellular infiltrates in animals primed with 2.5 mg isoprenaline following verapamil. Highly significant reduction in CK (C-max) activity was observed in animals administered with 40 mg magnesium chloride prior to isoprenaline compared to animals treated with isoprenaline alone (P < 0.001). In addition to this, significant delay in T-max of CK activity was observed in group treated with 40 mg magnesium chloride and isoprenaline compared to group treated with only isoprenaline (P < 0.01). The study clearly highlighted and confirmed the valuable role of magnesium chloride as cardioprotective agent.

Comparative study of omeprazole and famotidine in the treatment of duodenal ulcer.

In a double blind, multicenter, parallel group clinical trial in patients with symptomatic duodenal ulcers, 129 patients were randomized to receive either omeprazole 20 mg once daily (n = 65) or famotidine 40 mg once daily (n = 64) for 2 weeks, and if the ulcers were not healed, for a total of 4 weeks. Seventy four percent of these receiving omeprazole had healed ulcers after 2 weeks compared with 34.3% of those receiving famotidine (p < 0.001). At 4 weeks, the respective figures were 97.3% and 77.6% (p < 0.001). After 2 weeks of treatment, only 11.1% and 29.8% of omeprazole and famotidine treated patients respectively had day time pain (p < 0.02). Diary cards (successfully completed by 2/3rd of patients) showed that omeprazole treated patients required smaller amounts of antacids (p = ns). Over the first two weeks, ulcer healing rate was similar in smokers and non- smokers. No significant side effects were reported in either group. Omeprazole 20 mg/day provides more rapid relief of symptoms and heals a greater proportion of duodenal ulcers at 2 and 4 weeks than famotidine 40 mg/day.

A rapid method for evaluation of analgesic and anti-inflammatory activity in rats.

Carrageenin (2%) was used to produce edema and hyperalgesia; indomethacin, phenylbutazone, aspirin, ibuprofen, analgin, paracetamol and phenacetin were tested at different doses for anti-inflammatory and analgesic activity in the same rats as the peak for the edema reached at the end of 3rd hr and for the hyperalgesia at the end of 4th hr. Indomethacin, phenylbutazone and ibuprofen reduced edema and increased the pain threshold. Analgin and aspirin increased the pain threshold relatively at a low dose. Paracetamol and phenacetin were inactive in the doses tested. Carrageenin (2%) was observed to possess both phlogistic and allogenic properties.

Early beneficial effects of low dose oral methotrexate in rheumatoid arthritis.

The effect of low dose methotrexate pulse therapy was studied in 21 patients with active rheumatoid arthritis. Three doses of oral methotrexate 2.5 mg at 12 hourly intervals weekly was administered to all the patients. Patients were followed up for clinical, radiological and serological evaluation. Significant reduction in the number of painful and swollen joints, decrease in the duration of morning stiffness, fall in the erythrocyte sedimentation rate, and improvement in global assessment were seen in 15 patients (71.4%) by the end of 16 weeks. Five patients (23.8%) complained of minor gastric discomfort. None of the patients discontinued the treatment because of any side effect.