RESUMO
BACKGROUND: The available conventional antiepileptics do not afford cure or prophylactic treatment and henceforth there is always a quest to explore new targets for management of convulsions. In this perspective, dihydropyridine calcium channel blockers have been investigated in various animal models of epilepsy. Lercanidipine, a newer dihydropyridine calcium antagonist, is a potential candidate with its favourable lipid profile and longer duration of action. OBJECTIVE: (1) To evaluate the anticonvulsant effect of lercanidipine alone and in combination with standard drug in adult male Swiss albino mice. (2) To evaluate the muscle relaxant and spontaneous locomotor activity of lercanidipine in adult male Swiss albino mice. MATERIALS AND METHODS: Adult male Swiss albino mice weighing 20-30g were used to study the anticonvulsant, muscle relaxant and spontaneous locomotor activity using electroconvulsometer, rotarod and actophotometer apparatus respectively. The mice were divided into six groups of six animals in each group. Group 1 and 2 served as control (vehicle treated) and standard group respectively. Standard drug used to evaluate anticonvulsant effect is phenytoin sodium 25 mg/kg I.P. whereas muscle relaxant activity and locomotor activity is diazepam 4 mg/kg I.P., Group 3 and 4 received lercanidipine 1 and 3 mg/kg I.P., respectively. Anticonvulsant models included group 5 and 6 and they were given combination of phenytoin sodium 12.5 mg/kg I.P., with lercanidipine 1 and 3 mg/kg i.p, respectively. Abolition or reduction of tonic hind limb extension was considered as index of anticonvulsant activity whereas the balancing time of the animals in rod was recorded to asses muscle relaxant activity. The locomotor activity was recorded for 5 minutes. The data were analysed with one-way Analysis of Variance followed by post-hoc 'Dunnett t-test'. RESULTS: Lercanidipine given alone in a dose of 1 and 3 mg/kg had significantly reduced the tonic hind limb extension. Combination of lercanidipine (3 mg/kg) and phenytoin had offered 100% protection. The results also revealed that the test drug didn't impair the motor coordination and locomotor activity in mice. CONCLUSION: The present study had demonstrated that lercanidipine could be potential novel candidate for the treatment of convulsions.
RESUMO
OBJECTIVE: Ketamine administration is known to induce hemodynamic pressor response and psychomimetic effects which could be attenuated by appropriate premedication. The present study was designed to evaluate the effect of midazolam on hemodynamic stability and postoperative emergence phenomenon following ketamine anesthesia. METHODS: This was a prospective observational study including 30 adult patients with American Society of Anesthesiologists physical grades I and II scheduled for elective short surgeries under ketamine anesthesia. Patients were premedicated with midazolam (0.02 mg/kg intravenously) before the ketamine induction (1 mg/kg intravenously). Demographic data and hemodynamic variables were observed during the perioperative period. Pain score by visual analog scale score and psychomimetic effects were recorded postoperatively. FINDINGS: The mean ± standard deviation of heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate were decreased postoperatively (85.3 ± 11.4, 120.7 ± 8.2, 79.2 ± 5.5, 13.5 ± 1.8, respectively) compared to intraoperative period (88.53 ± 14.1, 123.83 ± 13.8, 83 ± 9.1, 14.13 ± 2.0, respectively). There was statistically significant decrease in systolic (P = 0.03) and diastolic (P = 0.002) blood pressure, but not with heart rate and respiratory rate. Eighty percent of patients had no pain at ½ hour and 1 hour, while this increased to 90% at 2 hours postoperatively. Mild emergence delirium was noted in 13.3% and 16.7% at ½ hour and 1 hour, respectively, which decreased to 13.3% at 2 hours. Dreams were noticed in 20%, 27% and 10% of patients at ½ hour, 1 and 2 hours after surgery, respectively. CONCLUSION: Midazolam premedication in ketamine anesthesia effectively attenuated the hemodynamic pressor response and postoperative emergence phenomenon. Hence, the combination of midazolam with ketamine can be safely used for short surgical painful procedures in adults.
