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Biomedical subjects

V K Bhargava

Publications and source records attributed to V K Bhargava.

At least 19 recordsLinked to original sources
PubMed2001

Anticonvulsant activity of omeprazole in rats.

Omeprazole has long been used as an effective agent to treat peptic ulcer. Recent studies have shown that in addition to inhibiting the H(+)-K(+)ATPase, it also inhibits carbonic anhydrase (CA) types I, II and IV. This led us to investigate its anticonvulsant effect in a rat model of electroconvulsion. Since other carbonic anhydrase inhibitors like acetazolamide induce tolerance upon repeated use, we tested the tolerance potential of omeprazole upon repeated administration of up to 1 week. The animals were divided into four groups receiving normal saline, omeprazole 0.5, 1 or 2 mg/kg intraperitoneally. CC(50), i.e. the threshold current inducing tonic hind limb extension in 50% of the rats was established using a technoconvulsometer which delivers currents of varying intensity via ear clip electrodes. The CC(50) was established 30 min after injection of omeprazole. In another group of rats, omeprazole 2 mg/kg was given for 6 days and the CC(50) determined on days 0, 1, 3 and 6. Also the concentration of omeprazole in the brain was determined using high performance liquid chromatography. The CC(50) in vehicle-treated rats was 98 mA, which increased to 126, 135 and 162 mA with 0.5, 1 and 2 mg/kg of omeprazole, respectively. On repeat-dose studies the CC(50) on day 0 was 96 mA, on day 1 166 mA, on day 3 129 mA and on day 6 102 mA. The average brain concentration of omeprazole was 53.2+/-6.9 ng/g of brain tissue. In conclusion, this study has shown omeprazole to be an effective anticonvulsant, but rapidly develops tolerance to its anticonvulsant action. This study can stimulate interest in the development of agents with dual function -- inhibition of CA as well as the accompanying Na(+)-K(+) ATPase -- and such agents may prove to be effective anticonvulsants without exhibiting tolerance.

Animals↗
PubMed2001

A randomized trial to compare the efficacy, safety, cost and platelet aggregation effects of enoxaparin and unfractionated heparin (the ESCAPEU trial).

OBJECTIVE: To compare the efficacy, safety, cost and effects on platelet aggregation of unfractionated heparin and low-molecular weight heparin in unstable angina patients. PATIENTS AND METHODS: Ninety-three patients with unstable angina were randomized to receive either unfractionated heparin (UFH) or enoxaparin in an open design clinical trial with blinded end point evaluation. The effects of the heparins on platelet aggregation were also compared. RESULTS: The composite end point of myocardial infarction, cardiac death, recurrent angina and need for intervention was observed in 62% of patients treated with UFH and in 37% of patients treated with enoxaparin (RR 1.7, 95% CI 0.75 to 3.71, p = 0.04). There was no difference in the frequency or severity of adverse events. A cost-effectiveness analysis showed both the heparins to be similar. Platelet aggregation was inhibited to a greater extent by UFH when compared to enoxaparin. CONCLUSIONS: Enoxaparin appears to be superior in efficacy to UFH and similar to UFH in safety. No difference in costs was detected in this study. The greater inhibition of platelet aggregation observed in the case of UFH compared to enoxaparin indicates that there may be more bleeding complications with UFH.

Adult↗
PubMed2001

Serotonergic mechanism in imipramine induced antinociception in rat tail flick test.

Substantial evidence has accumulated that spinally projecting serotonergic neurons modulate nociception. However, the exact receptor subtypes that mediate the antinociceptive response of serotonin within the spinal cord continue to be a subject of debate. Therefore, we explored the effect of serotonergic system on imipramine induced antinociception by using 5-Hydroxytryptamine-3 (5HT3) receptor antagonist ondansetron and 5-Hydroxytryptamine-2 (5HT2) receptor antagonist mianserine, and depletion of brain 5-Hydroxytryptamine (5HT) with p-chlorophenyl alanine (PCPA). Male wistar strain rats were pretreated with either ondansetron (0.5 mg/kg, i.p.) or mianserine (1 mg/kg, i.p.). After 15 minutes, rats received injection of imipramine (10 mg/kg). Nociception was assessed by tail-flick method. Imipramine (2 mg, 5 mg, 10 mg, and 20 mg/kg) produce antinociceptive response in the dose dependent manner. Prior treatment with 5HT3 antagonist, Ondansetron and 5HT2 antagonist, mianserine reduce the antinociceptive response of imipramine. In PCPA treated rats imipramine (10 mg/kg) failed to produce antinociception. These results indicate that the 5HT plays an important role in imipramine induced antinociception.

Adrenergic Uptake Inhibitors↗
PubMed2000

A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.

OBJECTIVE: The current study was designed to investigate drug utilisation in the management of unstable angina in India and to calculate the costs incurred by patients in the treatment of a single episode of unstable angina. METHODS: We conducted a prescription survey to examine the use of antianginal drugs in patients with unstable angina in a tertiary care Indian hospital. The use of concurrent medications such as antidiabetic, antihypertensive and lipid-lowering agents was also examined. Data on the cost of treatment, investigations, income, and family size were collected from the case histories or direct interviews with the patients/relatives. RESULTS: A total of 336 consecutive prescriptions were evaluated. Aspirin was the most frequently prescribed drug (98%) followed by nitroglycerin infusion (90%) and enoxaparin (52%). One of the heparins was used by 89% of all patients and beta-blockers by up to 62% of the patients. Besides antianginals, antihypertensive (49%) and antidiabetic (16%) drugs were commonly coadministered. The mean (+/- SD) cost of treatment of a single episode of unstable angina in the hospital was US $494 (+/- 271) against an annual per capita income of US $245. The mean (+/- SD) cost incurred by the patients due to drugs alone during the hospital stay was US $70 (+/- 18) and enoxaparin accounted for 60% of the expenditure due to drugs. CONCLUSIONS: The results of our study show that low-molecular-weight heparin, enoxaparin, is replacing unfractionated heparin in the treatment of unstable angina. In view of the use of costly new drugs, there is an urgent need for carrying out pharmacoeconomic analysis in developing countries as the treatment of a single episode of unstable angina imparts a considerable economic burden on the patient.

Aged↗
PubMed2000

Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

Animals↗
PubMed2000

Role of angiotensin-converting enzyme inhibitor, lisinopril, on spermatozoal functions in rats.

Angiotensin-converting enzyme is present in the male reproductive system but its role in the physiology of reproduction is not known. To see the effect of angiotensin-converting enzyme on spermatozoal functions, lisinopril, an angiotensin-converting enzyme inhibitor, was administered orally using two different doses (10 and 20 mg/kg/day) to rats. Both short-term (2 weeks) and long-term (6 weeks) effects of the drug were observed. Lisinopril treatment resulted in a marked decrease in sperm density, sperm motility and zona pellucida penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals was significantly lower when compared with spermatozoa from normal animals.

Acrosome↗
PubMed2000

Influence of kinnow juice on the pharmacokinetics of sustained release theophylline in healthy male volunteers.

The effect of kinnow juice on the pharmacokinetics of a single dose of sustained release theophylline was investigated in healthy male volunteers. In a two phased open cross-over randomized study, ten healthy male volunteers were given sustained release theophylline (300 mg) along with 300 ml of water or kinnow juice, a routinely used citrus juice in India. Blood samples were collected at different time points from 0-48 hours. Plasma was assayed for theophylline by a HPLC method and various pharmacokinetic parameters were calculated and compared. The theophylline levels were lower at all the time points with kinnow juice co-administration as compared to water but were significantly so only during the absorption phase from 1-4 hours. The values for all the pharmacokinetic parameters evaluated were on the lower side with kinnow juice except Tmax which was slightly delayed. None of these alterations was found to be significantly different. The results indicate that since there is an interference with the absorption of the drug, the patients may be advised not to consume kinnow juice when taking a slow release theophylline preparation and the monitoring of plasma concentrations of theophylline in patients who routinely consume kinnow juice in their diet might be helpful in better management of these patients.

Adult↗
PubMed2000

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.

Animals↗
PubMed2000

Effect of nimodipine on male reproductive functions in rats.

Nimodipine, a dihydropyridine calcium channel blocker, was administered orally using two different doses (40 mg and 60 mg/kg/day) to rats. Both short term (2 weeks) and long term (6 weeks) effects of the drug were observed. The drug administration resulted in a marked decrease in sperm density, sperm motility and acrozomal reaction. Zona-pellucida penetration by the sperm obtained from drug-treated animals was significantly lower when compared with sperm from normal animals. Nimodipine stimulated Ca2+ ATPase activity in isolated plasma membrane of rate spermatozoa. In conclusion, short term and long term administration of nimodipine has deleterious effect on male reproductive functions in rats.

Acrosome Reaction↗
PubMed1999

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.

Animals↗
PubMed1999

Effect of grapefruit juice on the pharmacokinetics of theophylline in healthy male volunteers.

The effect of grapefruit juice (GFJ) on the pharmacokinetics of a single dose of theophylline was examined in an open crossover study. Healthy male volunteers were given sustained release theophylline (300 mg) along with 300 ml of either water or GFJ. Blood samples (2 ml) were collected at different time points from 0 to 48 h. Plasma was assayed for theophylline by HPLC and various pharmacokinetic parameters were calculated. Theophylline levels were lower at all time points with GFJ coadministration as compared to water but were significantly lower only during the absorption phase from 1 to 4 h. Although the pharmacokinetic parameters were not significantly different between the two groups, all values were reduced except Tmax which was slightly increased. The results indicate that patients may be advised not to consume GFJ when taking slow-release theophylline and monitoring of plasma theophylline levels in patients consuming GFJ might be helpful in better management of patient care.

Adult↗
PubMed1999

Effect of ciprofloxacin on steady state pharmacokinetics of phenytoin in rabbits.

Present study was undertaken to determine if an interaction exists during co-administration of ciprofloxacin with phenytoin. Eight healthy male rabbits received oral phenytoin, 40 mg/kg, od, for 7 days. On day 7, phenytoin blood sampling was done at times 0, 0.1, 1, 2, 3, 4, 5, 6, 8 and 24 hr. From day 8 to 14, phenytoin was co-administered with oral ciprofloxacin, 70 mg/kg, od. On day 14, blood samples were collected as previously described. Pharmacokinetic analysis revealed significant decrease in steady state maximum concentration (Cmax), through concentration (Cmin), elimination half life (t 1/2 e) and the area under plasma time concentration curve (AUC0-24) of phenytoin when co-administered with ciprofloxacin. It warrants close monitoring of levels when these two agents are given simultaneously.

Animals↗
PubMed1999

Pharmacokinetics of phenytoin: unaltered by enalapril and amlodipine in rhesus monkeys.

A cross over single and multiple dose study was carried out to find out pharmacokinetic interactions between diphynylhydantoin (DPH) (35 mg/kg, p.o.) and antihypertensives enalapril (1.6 mg/kg; p.o.) and amlodipine (0.4 mg/kg, p.o.) in rhesus monkeys. Neither the plasma concentrations nor the pharmacokinetic parameters of DPH were altered by coadministration of enalapril or amlodipine, suggesting that enalapril and amlodipine can be safely administered to epileptic patients receiving phenytoin.

Amlodipine↗
PubMed1999

Effect of 'Mentat' on the pharmacokinetics of single and multiple doses o phenytoin in rabbits.

The effect of 'Mentat', a herbal preparation, was studied on pharmacokinetics of single and multiple doses of phenytoin in rabbits. No significant effect was found after single oral dose of 'Mentat' on single dose kinetics of phenytoin. However, 'Mentat' administration for 7 days increased the steady state kinetic parameters. Peak plasma phenytoin concentration, area under the implasma concentration and elimination half life were significantly increased and t-max was significantly reduced, indicating the suppression of phenytoin metabolism by 'Mentat'.

Animals↗
PubMed1999

Antinociceptive effect of gabapentin in the formalin test.

Gabapentin is an adjunctive drug for the treatment of resistant partial seizures. The antinociceptive effect of this drug was assessed by using the formalin pain test in rats. Although low dose gabapentin (10 mg/kg s.c.) was unable to alter pain scores, higher doses (30 and 90 mg/kg s.c.) significantly reduced them. Results suggest that gabapentin may modulate the pain perception produced by chemical irritants like formalin in rats.

Acetates↗