Effects of calcium channel blocker, nifedipine, on antidepressant activity of fluvoxamine, venlafaxine and tianeptine in mice

Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fluvoxamine, venlafaxine and tianeptine is limited. Hence, the present study was undertaken.Methods: The study was carried out in albino mice in two phases. In Phase I, antidepressant activity of nifedipine, fluvoxamine, venlafaxine and tianeptine were confirmed after their single dose administration using forced swim test (FST) and tail suspension test (TST) and their minimum antidepressant doses were determined. In Phase II, the effect of nifedipine on antidepressant activity of fluvoxamine, venlafaxine and tianeptine was studied by orally administering sub-antidepressant doses of these drugs for 28 days. FST and TST were carried out on 1st, 14th and 28th day of the study and change in immobility period was observed.Results: In Phase I, all the studied drugs exhibited dose dependent antidepressant activity in both FST and TST. Minimal antidepressant dose of nifedipine, fluvoxamine, venlafaxine and tianeptine was observed as 10, 25, 25 and 10 mg/kg respectively. In Phase II, combinations of sub-antidepressant dose of nifedipine (5 mg/kg) with sub-antidepressant doses of fluvoxamine (12.5 mg/kg), venlafaxine (12.5 mg/kg) and tianeptine (5 mg/kg) exhibited enhanced antidepressant activity when compared to the control group and individual drug groups after same duration of treatment.Conclusions: Nifedipine, fluvoxamine, venlafaxine and tianeptine possess antidepressant activity and nifedipine exhibits synergistic antidepressant activity with fluvoxamine, venlafaxine and tianeptine

Comparison of drug advertisements published in Indian and foreign journals

Background: Drug advertisements form one of the major sources for updating drug information by the medical professionals. It has been observed that Indian drug advertisements provide incomplete and poor quality of essential information. However, existing information on comparison of drug advertisements in Indian and foreign journals is limited. Hence, this study was planned to compare the drug advertisements published in Indian and foreign journals.Methods: A total of 200 drug advertisements, 100 each from Indian and foreign journals, were randomly selected excluding those of medical devices, surgical appliances, nutritional supplements and ayurvedic drugs. The drug advertisements from two sources were compared for drug groups, compliance to ‘Ethical criteria for medicinal drug promotion’ of World Health Organization (WHO), retrievability of cited reference(s) and mention of any additional information.Results: Drug groups advertised frequently in the Indian journals were those used for chronic diseases whereas chemotherapeutic agents topped the list in foreign journals. Brand names were mentioned in 100% advertisements in both categories of journals whereas information on other ingredients known to cause problems was not mentioned in any of the studied advertisements. Overall, compliance to WHO guidelines by advertisements was 54.6% in Indian journals and 68.2% in foreign journals. The two categories of journals didn’t differ significantly in retrievability of cited reference(s) and additional information except for information on drug storage which was significantly more mentioned in Indian journals.Conclusions: Drug advertisements in both Indian and foreign journals were incomplete for updating drug information by medical professionals.

Segmentation of Kidney Tumor

Medical Image Segmentation is a routine task in various clinical settings. There is a great interest in understanding the morphology of different human organs healthy or diseased. Until fairly recently, this task was done manually by clinical experts requiring years of difficult training tailored to specific medical fields. In this article we present a fully autonomous Machine Learning based method to segment Kidney and Tumor from human abdominal CT scans. Manually annotated data (210 datasets) were provided as a part of the Kits2109 MICCAI grandchallenge

Effect of tianeptine on seizure threshold and anticonvulsant activity of valproate, phenobarbitone and phenytoin in mice

Background: Depression is a common psychiatric comorbidity in patients with epilepsy and often remains untreated due to concern of antidepressant induced seizures. Tricyclic antidepressants, norepinephrine reuptake inhibitors and bupropion have been shown to increase the risk of seizures. Selective serotonin reuptake inhibitors and venlafaxine have shown both anticonvulsant and proconvulsant activity. The information on anticonvulsant effects of tianeptine, a newer antidepressant, is limited to few animal studies. In view of this, the present study was undertaken to investigate the anticonvulsant activity of tianeptine and its interaction with conventional antiepileptic drugs (AEDs) viz. valproate, phenobarbitone and phenytoin in mice.Methods: The study was carried out in 3 phases using healthy adult male mice. In phase I, effect of oral administration of tianeptine on seizure threshold was studied using electroconvulsive threshold method. In phase II and phase III, effect of tianeptine on median effective dose (ED50) of valproate, phenobarbitone and phenytoin was studied using maximal electroshock seizure (MES) test after administering tianeptine with these AEDs in various combinations. In phase II, drugs were administered orally once while in phase III, these were daily administered orally for 28 days.Results: In phase I, tianeptine increased electroconvulsive threshold in dose dependent manner but effect was significant only at 20 and 40 mg/kg (P<0.05 and 0.001 respectively). In phase II and III, tianeptine exhibited dose dependent reduction in ED50 of all the studied AEDs, however, significant reduction of ED50 of valproate and phenobarbitone (P<0.05 for both) was observed only when tianeptine was administered at 40 mg/kg, while significant reductions in ED50 of phenytoin were observed when tianeptine was administered as 20 and 40 mg/kg (P<0.05 and 0.01 respectively) and in phase III, significant reduction of ED50 value of valproate (P<0.01) and phenobarbitone (P<0.05) was observed with tianeptine at 40 mg/kg while reduction in ED50 of phenytoin was significant at all the studied doses of tianeptine with P<0.05 at 10 and 20 mg/kg and P<0.01 at 40mg/kg..Conclusions: Tianeptine exhibits anticonvulsant action which is synergistic with anticonvulsant effects of valproate, phenobarbitone and phenytoin suggesting that tianeptine may be a safe option in patients of epilepsy concurrently suffering from depression

Prescription patterns of antihypertensive drugs in a tertiary care hospital in India

Background: The present study was conducted to analyze the prescribing patterns and utilization of antihypertensive drugs at a tertiary care center in India.Methods: A cross-sectional analysis of prescriptions of patients of essential hypertension attending outpatient department of a tertiary care hospital during the period of December 2011 to March 2012 was done. Hypertensive patients with co-morbidities were excluded from study. The data were analyzed to find out demographic characteristics of patients, number of drugs prescribed per prescription, drugs, which are commonly prescribed, antihypertensive drugs used concurrently, percentage of drugs prescribed by generic name and over all drug utilization frequency.Results: During the study period, 465 prescriptions for hypertension were analyzed. This study revealed that most of the patients were on combination of antihypertensive drugs (67.97%) while 31.18% patients received mono therapy. Among mono therapy drugs, calcium channel blockers (CCB) (31.03%) were prescribed most. Utilization of other major drug classes as mono therapy in decreasing order is angiotensin-converting enzyme inhibitors (28.28%), diuretics (17.93%), beta-blockers (11.72%) and angiotensin receptor blockers (10.34%). Among those who were treated with drug combinations, 64.24% received 2-drug, 25.95% received 3-drug regimen and 8.54% received 4-drug regimen. In combination therapy, 2-drug combination consisting of a CCB and a diuretic was most commonly (24.14%) prescribed.Conclusions: This study represents the current prescribing patterns for anti-hypertensive drugs and provides the baseline data for similar studies in future, as patterns in prescribing antihypertensive drugs keep changing

An experimental study on the effect of isoniazid on the efficacy, plasma concentration and toxicity of paracetamol in Albino rats

Background: Paracetamol is used for symptomatic treatment of fever and pain with isoniazid and other anti-tubercular drugs in patients of tuberculosis. Literature has conflicting data regarding their interaction. Some studies show that isoniazid increases oxidative metabolism of paracetamol whereas some other suggest that isoniazid has an inhibitory effect. The present study was conducted to find out the possible interaction between paracetamol and isoniazid.Methods: The study was undertaken on Wistar strain of Albino rats. Group I and Group II animals were treated with paracetamol (500 mg/kg) and the combination of paracetamol (500 mg/kg) and isoniazid (30 mg/kg) respectively for 2 months. Blood samples were taken before and during the study for biochemical and histopathological studies of liver and renal functions and plasma paracetamol concentration was also evaluated.Results: Isoniazid decreased the plasma paracetamol concentration without affecting its analgesic activity. However, the hepatotoxic and nephrotoxic effects of paracetamol were found to be further aggravated by isoniazid co-administration.Conclusion: Isoniazid potentiates the hepatotoxic and nephrotoxic effects of paracetamol possibly due to hepatic enzyme induction by isoniazid

CHIRAL SWITCH- AN EMERGING STRATEGY IN THERAPEUTICS

During the last decade, drug chirality, more specifically the use of single enantiomers versus racemic mixtures has been in the forefront of discussions in scientific forums.This is because the left and right handed twins of a molecule behave quite differently from each other in a biological environment. This can frequently lead to an improvement in pharmacological and therapeutic profile of the molecule/drug. This understanding of the significance of stereo-chemistry coupled with advances in chemical technologies and further nudged by regulatory requirements has helped the increase in the development of individual isomers at the expense of racemic mixtures.Apart from the development of novel stereo-selective compounds, a number of racemates have been re-evaluated as potential single enantiomer agents with  the possibility of an improved pharmacological/therapeutic profile. These have been termed as Chiral Switches and have resulted in the re-birth of a number of agents as single enantiomers and have provided significant improvements over the racemic drug. Economic considerations are also playing a part with pharmaceutical companies increasingly using chiral switching as a marketing strategy to increase the patent longevity and profitability period of a drug. However, not all these switches have resulted in therapeutic superiority and in many instances, unpredicted adverse reactions have resulted. Before a switch to clinical use of single enantiomers is made, physicians should satisfy themselves from evidence based on well-conducted clinical trials that the chiral switch is cost-effective and improves the outcomes for patients.  KEY WORDS: Chirality, Chiral Switch, Enantiomer