Comparative efficacy of pregabalin and baclofen in the rodent chronic constriction injury model of neuropathic pain

Background: Neuropathic pain is associated with prolonged disability and is usually not responsive to conventional analgesics like NSAIDs and opioids. Even the recommended first-line drugs are effective in less than 50% patients. Thus, drugs with different mechanisms of action are needed. Baclofen, a GABA-B agonist has shown benefit in different types of neuropathic pains and is compared against pregabalin.Methods: The sciatic nerve was ligated in 2 groups of 6 rats each as per the chronic constriction injury model of neuropathic pain on day 0. After 14 days the effect of single doses of pregabalin (30mg/kg) and baclofen (5mg/kg) intraperitoneally were assessed over a 2 hours period. Thermal and mechanical hyperalgesia were assessed as measures of neuropathic pain by the hotplate and pin-prick method respectively.Results: Significant thermal and mechanical hyperalgesia was produced 14 days after sciatic nerve ligation in both the groups (p <0.05). Both pregabalin (p <0.001) and baclofen (p <0.01) were effective in decreasing thermal hyperalgesia throughout the two hours study period, but pregabalin was more effective as compared to baclofen (p <0.05) at 30, 60 and 120minutes. Both the drugs produced a significant decrease in mechanical hyperalgesia (p <0.01) throughout the study period. Again, pregabalin was the more effective drug (p <0.05) at all time points.Conclusions: Significant thermal and mechanical hyperalgesia was seen 14 days after sciatic nerve ligation. Both pregabalin and baclofen were effective in reversing the hyperalgesia, but pregabalin was the more effective of the two drugs at all time points.

Prescribing pattern of oral anti-diabetic agents in type 2 diabetes mellitus patients in a tertiary care hospital

Background: Prescription pattern studies are a tool for assessing the prescribing, dispensing and distribution of medicines. The main aim of assessing prescribing pattern is to facilitate rational use of medicines. So the main aim of the study was to assess the prescribing pattern of oral anti-diabetic agents in type 2 diabetes mellitus, to assess the rationality of the prescribed drugs and also to assess the pattern of co-morbid conditions associated with type 2 diabetes mellitus in a tertiary care hospital.Methods: This cross sectional study was conducted in the Department of Pharmacology in collaboration with Department of General Medicine. Study was conducted from 1st June 2016 to 31st Aug 2016 (3 months). A total of 100 patients were enrolled after taking written informed consent. A structured case recording form was used to record demographic details and prescription details. The rationality of prescriptions was assessed using American Diabetes Association guidelines 2015.Results: Majority of the patients were prescribed combination therapy (54%) followed by monotherapy (46%). Oral anti-diabetic agents used as monotherapy other than metformin were inappropriate. Among the patients receiving combination therapy majority were receiving a fixed dose combination which were inappropriate.Conclusions: Majority of the patients were receiving fixed dose combinations without justifiable pharmacokinetic/pharmacodynamic benefits. Such kinds of studies are required to improve rationality of prescription of drugs, decreasing morbidity and mortality of patients and decreasing the cost of treatment.

Comparative efficacy and safety of DPP-4 inhibitors and ?-glucosidase inhibitors as add on therapy in type 2 diabetes

Background: Diabetes mellitus (DM) is a spectrum of metabolic disorders as a consequence of different pathogenic mechanisms resulting in hyperglycemia. A genetic predisposition to develop ?-cell dysfunction synergizes with insulin resistance to lead to type 2 DM. Adequate management of type 2 DM requires institution of non pharmacological treatment followed by pharmacological treatment. Monotherapy is started initially followed by combination therapy (dual/triple). Sitagliptin, a DPP-4 inhibitor and voglibose, an ?-glucosidase inhibitor has been implicated as an add on therapy to metformin and glimepiride. So, we aimed to assess the efficacy and safety of the sitagliptin and voglibose as add on therapy to metformin and glimepitide in type 2 DM.Methods: This open label randomized control trial was conducted in the department of Pharmacology among patients attending medicine OPD of a tertiary care hospital. 80 patients were randomly divided into two groups of 40 patients each. group A:sitagliptin + metformin + glimepiride and group B:voglibose + metformin + glimepiride. Patients were followed every week for a period of 12 weeks. Data was analysed using paired t test, unpaired t test and chi square test.Results: There was a significant decrease in HbA1c, FPG and PPG in both the groups. Intergroup comparison at 4, 8 and 12 weeks showed a better improvement in glycemic control in group A as compared to group B.Conclusions: Sitagliptin showed a better glycemic control than that with voglibose in patients with uncontrolled type 2 DM on metformin and glimepiride.

Evaluation of levetiracetam and valproic acid as monotherapy on quality of life in patients of generalized tonic clonic epilepsy

Background: Quality of life plays an important role in patients of epilepsy and is the most neglected part during management. The antiepileptic drugs treatment results in seizure control but adversely affect the quality of life in patients.Methods: An observational analytical study was conducted in the Department of pharmacology with Department of Neurology of Himalayan Institute of Medical Sciences, Dehradun over 12 months. 85 patients fulfilling the inclusion criteria with diagnosis of generalized tonic clonic seizures (GTCS) were enrolled and divided into two groups based on physicians discretion and followed up for 12 weeks. Patients were evaluated for quality of life by QOLIE-10 self administered questionnaire at 0 and 12 weeks, assessed for seizure control and drug related adverse effects.Results: 85 patients were enrolled and divided into two treatment arms as per physician discretion, levetiracetam (41) and valproic acid group (44). Study drugs showed significant improvement in quality of life, levetiracetam showed mean change that was significantly greater than valproic acid (p=0.003) at 12 weeks. Patients who failed to achieve seizure control at 6 weeks were 17% patients in levetiracetam and 20% in valproic acid group, reason being non-adherence which was 17% and 20% respectively. Adverse events recorded with Levetiracetam (10), most common being increased sleep and with valproic acid (18), with most common being increased sleep and weight gain.Conclusions: Levetiracetam treatment resulted in better quality of life, with similar seizure control but decreased number of adverse effect then Valproic acid.

Gabapentin pre-treatment for pressor response to direct laryngoscopy and tracheal intubation: a randomized, double-blind, placebo controlled study.

Background: Laryngoscopy and endotracheal intubation are associated with an increase in blood pressure (BP) and heart rate (HR). The present study was conducted to evaluate the role of gabapentin in attenuation of these hemodynamic changes. Methods: Forty patients undergoing elective laparoscopic cholecystectomy under general anesthesia with standardized premedication and anesthetics were randomized to receive gabapentin or a matching placebo. The patients of Group I received gabapentin 600 mg orally 2 hrs before surgery and patients in Group II received a matching placebo. Patient’s HR, systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), were monitored before and after 1, 2, 5, and 10 mins of endotracheal intubation. Results: Comparison of SBP, DBP, and MBP at 1, 2, 5 and 10 mins after endotracheal intubation showed statistically significant attenuation in the gabapentin group when compared to placebo. Changes in the HR were not significant. Conclusion: Gabapentin 600 mg, given 2 hrs before induction is effective in attenuating the pressor response to laryngoscopy and tracheal intubation.

Gabapentin for post-operative nausea and vomiting: a pilot study.

Background: Gabapentin has been used in perioperative setting for the management of post-operative pain for surgery performed under general anaesthesia. Post-operative nausea and vomiting (PONV) even with the use of newer agents remains a major problem. The primary aim of this study was to see if gabapentin use decreased PONV. Methods: A total of 40 patients undergoing elective laparoscopic cholecystectomy under general anesthesia with standardized premedication and anesthetics were randomized to receive gabapentin or a matching placebo. The patients in Group I received gabapentin 600 mg orally 2 hrs before surgery and 12 hrs after the first dose. The patients in Group II received a matching placebo orally 2 hrs before surgery and 12hrs after the first dose. Patients in both groups received diclofenac sodium 75 mg i.m b.i.d for pain and ondensetron 4 mg i.v for PONV. Additional doses were given on demand and recorded. The treatment was double blinded. Results: The present study did not find significant reduction in PONV score and antiemetic consumption in gabapentin group when compared to a placebo for a period of 24 hrs. Conclusions: Gabapentin in the doses used was found to ineffective in post-operative nausea and vomiting in patients undergoing planned laparoscopic cholecystectomy with standardized pre-anaesthetic and anaesthetic medication.