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Biomedical subjects

V K Bhargava

Publications and source records attributed to V K Bhargava.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats.

The activity of nimodipine and nitrendipine against pentylenetetrazole (PTZ) induced seizures in Albino rats was studied alone and in combination with valproate. The median effective dose [ED50] of valproate, nimodipine and nitrendipine were initially determined. All the 3 drugs were injected i.p. 30 min before the induction of seizures. Seizures were induced by PTZ 85 mg/kg i.p., and subsequently the effect of combining ED50 doses of nimodipine and nitrendipine with ED50 dose of valproate was evaluated. ED50 of valproate and nitrendipine were 129 and 2.5 mg/kg respectively. ED50 of nimodipine could not be established since a dose-response relationship was not obtained. Hence, for the purpose of combination studies, 4 mg/kg of nimodipine was used. Both nimodipine (4 mg/kg) and nitrendipine (2.5 mg/kg) decreased the ED50 of valproate from 129 to 40 mg/kg. Both nimodipine and nitrendipine potentiate the activity of valproate against PTZ induced seizures and can be considered as potential adjuvant anticonvulsants which merit further study.

Animals↗
PubMed1999

Role of nitric oxide on insulin induced seizures in mice.

The role of nitric oxide (NO) on acute hypoglycemia-induced seizures in mice was investigated using insulin as the hypoglycemic agent. The NO precursor L-arginine in the doses of 150, 500 and 750 mg/kg exhibited a dose-dependent protective effect against seizures induced by 8 mu/kg insulin. The NO synthase inhibitor (L-NMMA) at the doses of 50 and 100 mg/kg potentiated the subconvulsive doses of insulin (2 mu/kg). The onset, duration, number of seizures and the mortality were noted in a 2 hr study period. The results of this study suggest than NO plays an important protective role in acute hypoglycemia induced seizures which are known to occur through the activation of NMDA receptors.

Animals↗
PubMed1998

Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy.

OBJECTIVE: To examine the effect of grapefruit juice on the bioavailability of carbamazepine in patients with epilepsy. METHODS: This was a randomized crossover study consisting of 2 phases. Ten patients with epilepsy who had received therapy with 200 mg carbamazepine 3 times a day for the previous 3 to 4 weeks participated. They were given either grapefruit juice or 300 mL water at 8 am along with 200 mg carbamazepine. Each treatment was separated by 2 days; subjects continued to receive carbamazepine therapy during the 2-day period. On both occasions, blood samples were collected at different time intervals between 0 to 8 hours. Carbamazepine levels were estimated by reversed-phase HPLC technique. RESULTS: Compared with water, grapefruit significantly increased the steady peak concentration (6.55 versus 9.20 microgram/mL), trough concentration (4.51 versus 6.28 microgram/mL), and area under the plasma concentration-time curve (43.99 versus 61.95 micrograms.h/mL) of carbamazepine. No significant effect was found in the time to reach peak plasma concentration. CONCLUSION: Grapefruit juice increases the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in gut wall and in the liver.

Adult↗
PubMed1998

Antimicrobial prescribing pattern in an Indian tertiary hospital.

550 prescriptions of the indoor patients receiving antimicrobial drugs in the Departments of Internal Medicine, Surgery, Urology and Paediatrics were analysed for drug utilization studies. The prescribing frequency of one antimicrobial per prescription was maximum in Surgery and Urology (52.52%) and Internal Medicine (50.51%) whereas prescribing frequency of two antimicrobials was maximum in Paediatrics (59.9%). In all the departments, quinolones, aminoglycosides, cephalosporins and penicillins were frequently prescribed among which amikacin, ciprofloxacin, cefotaxime and cloxacillin were most preferred drugs, with a general tendency of prescribing newer antimicrobials. In majority of cases selection of antimicrobials was not based on microbiological confirmation. It is suggested that the use of newer and expensive antimicrobials should be kept reserved only for serious and life threatening situations.

Anti-Infective Agents↗