Résumé
Neurosteroids are natural or synthetic steroid derivatives which act locally in brain by modulating neuronal excitability. The objective of this study is to analyze available literature on classification, biosynthesis and mechanism of action, and therapeutic potential of neurosteroids. A review of literature pertaining to neurosteroids published from inception to 2018 was carried on data bases like PUBMED, Google Scholar and Science Direct. The search terms used were neurosteroids, neuro-active steroids, ganaxolone and GABA-A receptor modulators. Review of literature suggests neurosteroids are powerful neuro-modulators, involving rapid non-genomic and non-hormone receptor mechanisms. They are classified based on structure as pregnane, androstane and sulphated neurosteroids, and based on function as excitatory or inhibitory neurosteroids. They act via GABAA receptor (primarily), rho- GABA (?GABA), NMDA-glutamate and sigma receptor modulation. The inhibitory neurosteroids demonstrate sedative, anxiolytic and anticonvulsant actions, whereas the excitatory agents produce memory enhancing and anxiogenic effects. They show efficacy in various CNS and psychiatric conditions like epilepsy, anxiety, depression, learning and memory disorders and substance abuse. Endogenous neurosteroids have limited clinical use due to low bioavailability, lack of specificity and unwanted effects. Hence, synthetic agents like alphaxalone, ganaxolone, sepranolone and brexanolone which have better bioavailability and specificity, are being investigated in various phases of clinical trials. Neurosteroids are novel endogenous compounds with neuro-modulatory function and show promising effects in therapy of various neurological and psychiatric conditions. Further studies that prove their long term efficacy and safety may revolutionize the clinical approach to therapy of these conditions.
Résumé
Background: Cardiovascular disease is one of the major causes of mortality and morbidity in a developing country like India. These patient’s prescription contains multiple drugs to reduce the mortality and morbidity and they also contain drugs for treatment of co morbidities leading to polypharmacy. The main objective of the study was to identify the pattern of drug- drug interaction (DDI) in patients on cardiovascular drugs with various co existing morbidities.Methods: This study was conducted in the Department of General Medicine of a tertiary care center. Prescription of 200 patients were analysed for demographic details like gender, age, comorbidities and drugs prescribed. DDI were assessed using Micromedex software.Results: In this study, conducted on the prescription of 200 elderly patients, 13 (66%) prescription had 408 DDI, of which 158 (39%) were major, 246 (60%) were moderate and 1 (0.02%) was contraindicated and 3 (0.007%) were minor.Conclusions: It can be concluded from the present study that the risk of DDI increases with the increase in number of drugs in the prescription and there is increase in number of drugs in the prescription with the increase in number of co morbidities. The antiplatelet and anticoagulant group of drugs were responsible for majority of DDI, followed by antihypertensives and hypoglycaemic agents. Most of these DDI could be avoided with slight modification in the dosage regimen based on the pharmacokinetics and pharmacodynamics of the drug.
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Background: Diabetes Mellitus is a spectrum of common metabolic disorders whose management mainly lies in treating the patients with oral hypoglycaemic drugs and insulin along with the dietary and lifestyle modifications. Lipodystrophy is the most neglected adverse drug effect caused by injecting insulin. The main objective of this study was to assess the prevalence of lipodystrophy at the insulin injection sites in patients suffering from diabetes mellitus (Type 1 and Type 2).Methods: A cross-sectional study was conducted in the Department of Endocrinology on 250 diabetic patients taking insulin injections based on inclusion and exclusion criteria. The demographic features and anthropometric measurements were noted. Insulin injection sites were examined clinically by inspection and palpation for presence of swelling like lipodystrophy, injection marks and signs of allergy like erythema etc. Lipodystrophy was graded from 0-3 and denoted as lipohypertrophy or lipoatrophy. The results were tabulated and presented accordingly.Results: In this study, out of 250 patients 17 (6.8%) patients presented with insulin induced lipodystrophy. Lipohypertrophy was the most common presentation and only one case presented with lipoatrophy.Conclusions: It can be concluded from the present study that lipodystrophy which is an important adverse effect due to insulin injection needs to be monitored regularly in every patient taking insulin for better control of glucose levels.
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Background: Chemotherapy induced nausea and vomiting is the most distressing side effect of cancer chemotherapy. It can seriously impact patient抯 quality of life, influence the adherence to chemotherapy and progression free survival causing a delay or refusal of potentially life-saving therapy. The objective of this study was to compare the efficacy of palonosetron with ramosetron in achieving complete response to the chemotherapy.Methods: This was a prospective randomized open-label study conducted on 130 patients admitted in Medical Oncology ward of a Tertiary Care Hospitals, Bangalore, India. Patients were randomized to receive either palonosetron 0.25 mg or ramosetron 0.3 mg I.V. along with aprepitant and dexamethasone 30 minutes prior to chemotherapy and were followed up for a period of 5 days post chemotherapy. The observations such as number and severity of vomiting and nausea, the outcome was assessed at the end of 5 days. Pearson抯 Chi-square test was used to demonstrate the difference between both the study groups with respect to various categorical data.Results: The complete response rate in delayed phase was more significant in patients who received palonosetron than patients who received ramosetron (72.3% vs 50.8%). Total control was achieved in 38.5% patients with palonosetron as compared to 15.4% patients with ramosetron.Conclusions: Palonosetron is more efficacious than ramosetron in controlling chemotherapy induced nausea and vomiting especially in delayed phase of emesis.
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Linezolid is the oxazolidinone group of antibiotic with wide range of activity against the gram positive bacteria including methicillin resistant staphylococcus aureus and penicillin resistant pneumococci and vancomycin resistant enterococci. Patients who are on linezolid were reported to have reversible myelosuppression especially thrombocytopenia and anaemia. Since there are less number of studies regarding the occurrence of thrombocytopenia and the risk factors associated with it, this study was undertaken to evaluate the occurrence of linezolid induced thrombocytopenia and its association with risk factors. It was a systematic review with synthesis of available literature in English language. Articles were retrieved using search terms included “linezolid”, “and”, “or”, “thrombocytopenia” from Clinical key and PubMed, published during 2000 - 2017. Out of 16 studies retrieved, only 7 studies were analysed based on inclusion and exclusion criteria; of them, 3 were found to be prospective and retrospective cohort each and only one was retrospective cross-sectional study. The occurrence of linezolid induced thrombocytopenia range from 18-50% with normal renal function and 57% of incidence associated with renal insufficiency patients. The risk factors were found to be dose of linezolid >18-27mg/kg, body weight of subjects <55kg, creatinine clearance <88.39 to 60ml/min/1.73m2 and baseline platelet count <200*103/mm3, serum albumin concentration, serum creatinine, concomitant caspofungin therapy and duration of linezolid therapy.
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Radiation recall dermatitis (RRD) is the appearance of skin reactions in previously irradiated skin which is triggered by the administration of certain drugs. Surgery, chemotherapy, and radiotherapy are the mainstay of treatment in breast cancer. RRD induced by trastuzumab has been rarely reported in India. This is a case report of a 56-year-old woman presented to the medical oncology outpatient department of our hospital with breast lump, and she was diagnosed to have human epidermal growth factor receptor 2 (HER-2/neu) positive invasive ductal carcinoma of left breast of stage T2N3cM0. She was treated with neoadjuvant chemotherapy, and she underwent modified radical mastectomy with axillary lymph node dissection. The treating oncologist was planned to start on adjuvant chemotherapy with injection trastuzumab for every four weeks, for 15 cycles. Patient received first dose of injection trastuzumab (450 mg) intravenously in the right (contralateral) arm and developed painful, swollen, erythematous blisters, and maculopapular rashes following the sharp linear borders of her previous radiation fields. She was reviewed by the medical oncologist and diagnosed as a rare case of RRD and treated with topical betamethasone cream. Causality assessment for RRD to trastuzumab was done using Naranjo and WHO-UMC scale and found to be in the category of probable and probable/ likely respectively.