Bharti Chogtu

Statin use and risk of diabetes mellitus

The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used in the primary and secondary prevention of cardiovascular diseases to lower serum cholesterol levels. As type 2 diabetes mellitus is accompanied by dyslipidemia, statins have a major role in preventing the long term complications in diabetes and are recommended for diabetics with normal low density lipoprotein levels as well. In 2012, United States Food and Drug Administration released changes to statin safety label to include that statins have been found to increase glycosylated haemoglobin and fasting serum glucose levels. Many studies done on patients with cardiovascular risk factors have shown that statins have diabetogenic potential and the effect varies as per the dosage and type used. The various mechanisms for this effect have been proposed and one of them is downregulation of glucose transporters by the statins. The recommendations by the investigators are that though statins can have diabetogenic risk, they have more long term benefits which can outweigh the risk. In elderly patients and those with metabolic syndrome, as the risk of diabetes increase, the statins should be used cautiously. Other than a subset of population with risk for diabetes; statins still have long term survival benefits in most of the patients.

Evaluation of diuretic activity of Amaranthus spinosus Linn. aqueous extract in Wistar rats

ETHNOPHARMACOLOGICAL RELEVANCE Traditional Siddha medicine literature claims that the Amaranthus spinosus Linn. (family: Amaranthaceae) whole plant possesses diuretic property. AIM OF THE STUDY To evaluate the diuretic potential of Amaranthus spinosus aqueous extract (ASAE) in rats. MATERIAL AND METHODS Different concentrations of ASAE (200, 500, 1000, 1500mg/kg), thiazide (10mg/kg) and vehicle were orally administered to rats (n=6 animals per group) and their urine output was collected after 24h. Volume, pH, Na(+), K(+) and Cl(-) concentrations of urine were estimated. RESULTS ASAE produced increase in Na(+), K(+), Cl(-) excretion, caused alkalinization of urine, showed strong saluretic activity and carbonic anhydrase inhibition activity. These effects were observed predominantly at 500mg/kg dose and there was no dose-response relationship. CONCLUSION Our study strongly suggests that the Amaranthus spinosus is acting as a thiazide like diuretic with carbonic anhydrase inhibitory activity which restates the claim as diuretic herb in Siddha medicine.

Comparison of the efficacy of carbamazepine, gabapentin and lamotrigine for neuropathic pain in rats

Background: Neuropathic pain in cancer patients remain a treatment challenge. Many of the anticancer drugs have to be abandoned because patients develop neuropathic pain. Several antiepileptic drugs like carbamazepine, phenytoin, lamotrigine, felbamate are effective in neuropathic pain and trigeminal neuralgia. However, their efficacy varies. Aim: The aim of this study is to compare the efficacy of antiepileptic drugs in neuropathic pain induced by anticancer drugs. Materials and Methods: Neuropathic pain was induced in rats by injecting 4 doses of paclitaxel. The rats were divided into four groups of six animals each. Group I was treated with oral carbamazepine (cbz) 100 mg/kg, group II received oral gabapentin (gbp) 60 mg/kg, and group III was treated with oral lamotrigine (lam) 40 mg/kg and group IV was the control group. Behavioural testing for thermal hyperalgesia and mechanical hyperalgesia was assessed from 26th day of paclitaxel administration to next five days by hot plate method and Randall Siletto test, respectively, in all the four groups. One way analysis of variance followed by Scheffes post hoc test was used for statistical analysis. Results: In thermal hyperalgesia lam treated group was found to be significantly (P < 0.001) superior to cbz and gbp treated group. In mechanical hyperalgesia, lam group showed significant response (P < 0.05) as compared to gbp group. However, the gbp treated group showed a significant (P < 0.01) improvement after three days of treatment. Conclusions: In paclitaxel induced neuropathic pain, lamotrigine appears to be a promising drug. The difference in responses shown by different antiepileptics’ depends on the etiology of the underlying mechanisms in neuropathic pain.

Statins in Asthma: Potential Beneficial Effects and Limitations.

Asthmas sustenance as a global pandemic, across centuries, can be attributed to the lack of an understanding of its workings and the inability of the existing treatment modalities to provide a long lasting cure without major adverse effects. The discovery of statins boosted by a better comprehension of the pathophysiology of asthma in the past few decades has opened up a potentially alternative line of treatment that promises to be a big boon for the asthmatics globally. However, the initial excellent results from the preclinical and animal studies have not borne the results in clinical trials that the scientific world was hoping for. In light of this, this review analyzes the ways by which statins could benefit in asthma via their pleiotropic anti-inflammatory properties and explain some of the queries raised in the previous studies and provide recommendations for future studies in this field.

Pedal edema with olanzepine

Olanzapine, an atypical antipsychotic is considered superior to its conventional congeners. Here we report two cases of pedal edema secondary to olanzapine. In both cases the systemic causes of pedal edema were ruled out. On reducing the dose of olanzapine, pedal edema regressed and completely resolved after stopping the drug. So we attribute the edema to olanzapine therapy. As the definitive cause and further consequences of pedal edema are not known, hence stringent monitoring of adverse effects of this drug is required.

Capreomycin-induced optic neuritis in a case of multidrug resistant pulmonary tuberculosis

A patient of multidrug-resistant pulmonary tuberculosis was prescribed an anti-tubercular regimen containing capreomycin. Patient developed optic neuritis 3 months after starting treatment. Investigations did not reveal any specific cause for this ocular condition and on discontinuing capreomycin his vision recovered. We conclude that capreomycin is the cause of reversible optic neuritis in our case.

A prospective, randomized study: Evaluation of the effect of rosuvastatin in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

Objectives: Statins by their anti-inflammatory and endothelial stabilizing effect can be beneficial in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH). The present study was done to evaluate the effect of rosuvastatin on pulmonary functions and quality of life (QOL) in patients with concomitant COPD and PH. Materials and Methods: It was a prospective, randomized, double-blind, placebo-controlled, study conducted in patients with COPD and PH. A total of sixty patients were assigned to receive either rosuvastatin 10 mg or placebo once a day in addition to their conventional treatment for 12 weeks. Routine blood investigations, pulmonary functions, echocardiogram, exercise capacity, and QOL using a questionnaire were assessed at the baseline and after 12 weeks. Results: In patients of rosuvastatin group, there was a statistically significant increase in peak expiratory flow rate (PEFR) (P = 0.04) but no significant change in other pulmonary functions: Forced vital capacity (FVC), forced expiratory volume at 1 s (FVC, FEV1, FEV1/FVC), and echocardiogram parameters. There was a significant increase in 6-min walk test (6-min walk distance) (P = 0.03) at the end of 12 weeks. On comparing with placebo, rosuvastatin showed a significant reduction (P = 0.045) in COPD exacerbations while adverse effects did not differ. Conclusion: Statins have a favorable effect on patients with COPD and PH regarding the improvement in PEFR, COPD exacerbations, and exercise capacity. Such effects can be beneficial in these patients and more so in patients with concomitant coronary artery disease or hyperlipidemia where long-term benefits of statins have been established.

Rifampicin-Induced Concomitant Renal Injury and Hepatitis.

Adverse drug reactions are not unusual during Anti-Tubercular Therapy (ATT). One of the common complications of anti-tubercular treatment is drug induced hepatitis and renal insufficiency has also been reported. Renal failure and/or hepatitis encountered during treatment of tuberculosis can have varied aetiologies: drug induced, concomitant viral infection, pre-existing co-morbidities or a combination of these. Since, hepatitis and/or renal insufficiency can be life threatening a prompt diagnosis is warranted, where drugs should be kept as one of the important cause. Identifying the drug helps in treating hepatitis and/or renal insufficiency along with helping the physician to change the combination of ATT regimen. Rifampicin is one of the most important first line drugs in the treatment of tuberculosis. Hepatitis, epigastric distress, anaemia, thrombocytopenia, and interstitial nephritis are reported adverse drug reactions to rifampicin. As per literature rifampicin induced renal toxicity is usually seen on rifampicin re-exposure, or rifampicin administration on alternate days, both being present in this case. Here we are reporting a case of ATT induced renal failure with concomitant hepatitis where rifampicin was suspected to be the cause.

Stevens Johnson syndrome and neurotoxic effects of metronidazole

Sir, Stevens Johnson syndrome (SJS) is a severe cutaneous adverse drug reaction and predominantly involves the skin and mucous membranes. In most cases developing SJS, the risks remain unidentifiable.[1] Drugs that commonly cause SJS are sulphonamides, nevirapine, allopurinol, lamotrigine, aromatic anticonvulsants, and oxicam nonsteroidal anti-inflammatory drugs (NSAIDs). Drugs with long half-lives are more likely to cause such fatal reactions than those with short half-lives.[2] In Drug watch published in Jan–Feb 2014 issue of the Indian Journal of Pharmacology, the authors have reported a case of metronidazole-induced SJS in a patient in whom symptoms started 6 hours after first dose and progressed after second dose.[3] As mentioned by authors, there is one case reported by Piskin and Makkes in which patient started developing symptoms 1 day after initiating of metronidazole. Authors have also reported that the cutaneous drug reaction was accompanied by early central nervous system (CNS) symptoms like dizziness, confusion, convulsions, and loss of consciousness for 15-20 min. They consider the CNS manifestations to be a part of SJS. However, in our view, the CNS symptoms experienced in this case can be explained separately as metronidazole-induced adverse effect. Though, metronidazole-induced encephalopathy is relatively rare,[4] it needs to be considered because of its use in both medical and surgical patients. CNS toxicity with metronidazole does not seem to be a doseor duration-related phenomenon.[5] Magnetic resonance imaging (MRI) abnormalities are seen in most patients. Theories suggested for CNS changes include axonal swelling with increased water content due to toxic injury or localized reversible ischemia due to vascular spasm.[6] It can also be due to interstitial edema or purkinje cell damage due to binding of the metronidazole to neuronal ribonucleic acid (RNA), causing inhibition of protein synthesis and resulting in axonal degeneration.[6] The prognosis of metronidazole-induced CNS adverse effects is excellent, once metronidazole is stopped.

Development of a Predictor Model for Quality of Life in Cancer Patients with Adverse Drug Reactions due to Cancer Chemotherapy.

Cancer is one of the leading causes of morbidity and mortality worldwide. There are various detrimental symptoms experienced by a cancer patient due to the disease and the undergoing treatment which adversely affects the Quality of Life (QOL) in these patients. Therefore, QOL and its evaluation have turned out to be progressively vital in the health care system. Hence, the aim of our study was to develop a predictor model to predict the QOL in cancer patients receiving chemotherapy. The study was carried out in the Department of Radiotherapy and Oncology, Kasturba hospital, Manipal, a tertiary care hospital. Predictor model was developed to predict the Quality of Life Scores (QOLS) using multivariate regression analysis. A total of 387 patients participated in the study. Mean age of the patients was 50.85 ± 11.82 years (95% CI, 49.66-52.03). In our study, 16.54% had poor global health status/QOL, 72.35% had average and 11.11% had a high global health status/QOL. A significant difference was found in the QOLS based on the age group, site of cancer, drugs used in treatment of cancer, age as a predisposing factor and organ system affected due to ADRs (respiratory system, sensory system, skin and appendages). In the predictor model, the Coefficient of determination R-square (R2) was found to be 0.3267 indicating that 32.67% of the variation in the ‘quality of life score’ is explained by the independent variables included in the model. The F (45, 341) = 3.67, p < 0.001 indicating the overall significance of the regression model. Thus, the study showed that there are various predictors that can assess the QOL in cancer patients which can further serve as a guide to implement timely interventions to improve patients QOL.