Drug-induced parkinsonism

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Survival of patients with metastatic bladder cancer in the Russian Federation: results of a multicenter registry study URRU

Background. Data on the overall survival (OS) of patients with metastatic bladder cancer (BCa) is rarely published.The objective of the URRU register study is to assess OS and collect information on the administration of different treatments in patients with metastatic BCa in routine clinical practice in Russia.Materials and methods. Patients were retrospectively identified in 9 oncology centers in different regions of Russia and included in the study if they were diagnosed with metastatic BCa between January 2017 and January 2018. We collected anonymized data online, including demographic characteristics of patients, details of their therapy, and outcomes.Results. This study included 246 patients. Their mean age upon the diagnosis of metastatic BCa was 72 years with 60.6 % of patients over 70 years of age. The proportion of males was 74.8 %. The histological subtype of BCa (urothelial carcinoma, etc.) was identified in 70.3 % of cases. Ninety-two patients (37.4 %) received pharmacotherapy. The most common treatment option was chemotherapy (76 %); the most common drug combination was gemcitabine and cisplatin (41.3 %). Immunotherapy was used in 19.6 % of patients; 13.6 % of participants received more than two lines of therapy. Three-year OS rate was 10.6 %; median OS was 7 months (95 % confidence interval (CI) 5.4-8.6). Patients receiving systemic therapy demonstrated significantly longer survival than those receiving no therapy (21 months; 95 % CI 17.38-24.62 vs 3 months; 95 % CI 1.79-4.22; p <0.0001). Patients receiving immunotherapy had better survival than individuals receiving chemotherapy (median OS 34.5 months vs 18 months; p = 0.003).Conclusion. The survival rates in the URRU study were relatively low, which can be attributed to the fact that only one-third of patients received pharmacotherapy and very few patients received immunotherapy. Second and subsequent lines of therapy were rarely used in patients with progressive disease. The implementation of novel treatments, including immune checkpoint inhibitors, will increase the survival of BCa patients.

Peroxiredoxin-6 is a Guardian of lung pathophysiologies

: The moonlighting protein, Prdx6 exhibits peroxidase activity, phospholipase activity and lysophosphatidylcholine acyl transferase (LPCAT) activity. Although it is ubiquitous in expression, its level is prominently high in the lung. Prdx6 has been known to be an important enzyme for the maintenance of normal lung physiologies including, anti-oxidant defense, lung surfactant homeostasis and cell signaling. Studies further unveiled that the altered activity (peroxidase or aiPLA2) of this enzyme is linked with various lung pathologies or diseases. In the present article, we attempted to address the various pathophysiologies or disease conditions (like lung ischemia, hyperoxia, lung cancer, emphysema and acute lung injury) wherein prdx6 is involved. The study implicates that Prdx6 could be used as a common drug target for multiple lung diseases. Important future insights have also been incorporated.

Comparative Study of Aragvadha Phalamajja (Cassia fistula Linn.) w.s.r. to its Sangrahana Vidhi

Ayurved advocates that drug should be collected with proper classical methods. In Ayurvedic texts, specific time, season and procedures or methods have been highlighted for getting better potency, efficacy and therapeutic properties of drug by describing the standard methods of drug collection and preservation in details. Now a day, due to lack of proper traditional knowledge and time very few people bother to follow all these methods of collection given by Acharya. Hence, the potency of medicines is of question. Aragvadha (Cassia fistula Linn.) has been popular as a common drug of choice treatment since ancient time. Classic text like Charaka Samhita has quoted the classical and particular method for the collection and preservation of Aragvadha Phalamajja (Cassia fistula Linn.). Acharya Charaka has quoted this collection method of Aragvadha Phalamajja(Cassia fistula Linn.)as follows- The good qualities of collected pods should be kept covered in river bed sand for seven days. After seven days these pods should be removed and kept in sunlight for some time. And thereafter, fruit pulp (phalamajja) should be extracted and stored in a clean vessel. Therefore, study of classically collected Aragvadha Phalamajja (Cassia fistula Linn.) and Market sample of Aragvadha Phalamajja (Cassia fistula Linn.) was carried out.

Piperacillin–Tazobactam-Induced Immune Thrombocytopenia: A Case Report

Drug-induced immune thrombocytopenia is an isolated thrombocytopenia caused by accelerated platelet destruction from drug-dependent, platelet-reactive antibodies. Heparin-induced thrombocytopenia is the most common drug-induced immune thrombocytopenia. Common implicated antibiotics for drug-induced immune thrombocytopenia include ceftriaxone, trimethoprim–sulfamethoxazole, vancomycin, and penicillin. The platelet nadir can be less than 20 × 10 (9)/L and typically occurs within 1 to 2 weeks of exposure to the inciting drug. Although rare, drug-induced immune thrombocytopenia can be fatal. Diagnosis is made by excluding other causes of thrombocytopenia. Laboratory testing for drug-dependent antiplatelet antibodies is often helpful but not required. Thrombocytopenia typically improves within 1 to 2 days of drug discontinuation and platelet count returns to normal within a week. Identifying and discontinuing the implicated medication is key to prevention of serious complications. A patient case of drug-induced immune thrombocytopenia is described after initiation of empiric piperacillin–tazobactam for refractory right foot cellulitis in the setting of right fourth toe diabetic ulcer.

A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors

The H1N1 pandemic in 2009 and the H5N1 outbreak in 2005 have shocked the world as millions of people were infected and hundreds of thousands died due to the infections by the influenza virus. Oseltamivir, the most common drug to block the viral life cycle by inhibiting neuraminidase (NA) enzyme, has been less effective in some resistant cases due to the virus mutation. Presently, the binding of 10 chalcone derivatives towards H5N1 and H1N1 NAs in the non-catalytic and catalytic sites was studied using molecular docking. The in silico study was also conducted for its drug-like likeness such as Lipinski Rule, mutagenicity, toxicity and pharmacokinetic profiles. The result demonstrates that two chalcones (1c and 2b) have the potential for future NA inhibitor development. Compound 1c inhibits H5N1 NA and H1N1 NA with IC50 of 27.63 µM and 28.11 µM, respectively, whereas compound 2b inhibits NAs with IC50 of 87.54 µM and 73.17 µM for H5N1 and H1N1, respectively. The in silico drug-like likeness prediction reveals that 1c is 62% better than 2b (58%) in meeting the criteria. The results suggested that 1c and 2b have potencies to be developed as non-competitive inhibitors of neuraminidase for the future development of anti-influenza drugs.

A STUDY DESCRIBING THE USAGE PATTERN OF ANTIMICROBIALS WITH INSIGHTS INTO ANTIMICROBIAL DRUG-DRUG INTERACTIONS AMONG ADULT POPULATION IN HOSPITAL SETTINGS

The study aims to describe the use of antimicrobials among adult population in hospital settings with emphasis on the antimicrobial therapy provided and potential antimicrobial drug-drug interactions identified. 108 adult patients who were prescribed antimicrobials were considered for this retrospective study which was carried out over a period of 3 months. It was identified that antimicrobials prescribed were largely antibacterial (91.2%) with Piperacillin + Tazobactam (24 times) and Cefuroxime (15 times) being the most commonly prescribed antimicrobials on treatment and discharge, respectively. Upon assessing the antimicrobial therapy, it was identified that antimicrobials were predominantly prescribed empirically (57.4%) and monotherapy was observed more, both on treatment (52.8%) and discharge (47.2%). A total of 79 different potential antimicrobial drug-drug interactions were identified, out of which, 64.6% were major interactions. Ciprofloxacin + Metronidazole drug-drug interaction was the most common drug interaction observed 6 times, whereas clarithromycin and ciprofloxacin caused the greatest number of interactions with a frequency of 10 instances each. Ondansetron was the non-antimicrobial drug that caused the greatest number of drug interactions (21.2%). The present study reinforces that antibiotics and other antimicrobials are a group of very commonly prescribed medications in the hospital with a variety of indications. An important, but often unheeded aspect of therapy is antimicrobial interactions with other drugs, which this study has highlighted.