Pharmazie最新文献

Medication-induced weight gain can be frustrating to patients and health care providers. Drug-induced weight gain is a profound side effect of numerous commonly used medications. The present study aimed to investigate FAERS reports about drug-induced weight gain in the last ten years. Using the US FDA Adverse Event Reporting System (FAERS) between 2012 and 2021, a retrospective, descriptive analysis was conducted to analyze the major reported Adverse Events about weight gain. During the last ten years, 137370 reports were submitted to FAERS about drug-induced weight gain. The most common drugs that are reported by the patients and that are associated with weight gain were risperidone (11.55%), adalimumab (3.94%), pregabalin (3.86%), aripiprazole (3.1%), etanercept (2.72%), and prednisone (2.70%). In conclusion, the present study showed that drug-induced weight gain is a common side effect of several medications frequently used to treat chronic diseases. Healthcare providers should educate their patients about the medicines that may cause weight gain.

Hypothyroidism is a common health problem among elder women. However, conflicting results were observed regarding the association between levothyroxine treatment and osteoporosis risk. Therefore, the current study aimed to evaluate the effect of levothyroxine replacement therapy on osteoporosis risk in the Saudi population. This study was a matched case-control study conducted from June to August 2020. Data were extracted from the electronic medical records and included sociodemographic, clinical characteristics, comorbid conditions, levothyroxine replacement therapy dose, duration, concomitant therapy, and bone mineral density. Cases were matched with controls (1:1 basis) by age; the study included 256 cases and 256 controls. In the multivariate conditional logistic regression analysis, thyroxine use was independently associated with an increased likelihood of osteoporosis. Therefore levothyroxine use in elderly females was associated with an increased risk of osteoporosis, and hence, clinicians must be aware of the levothyroxine replacement therapy outcomes in postmenopausal females at risk of osteoporosis.

Acute disseminated encephalomyelitis (ADEM) is a rare and immune-mediated inflammatory disorder of the central nervous system (CNS) that can be triggered by infections and vaccinations. To date, only anecdotal case studies have reported the association between ADEM incidence and seasonal influenza vaccines, and multiple studies have found no association. This study aimed to investigate the association between the incidence of ADEM and seasonal influenza vaccines in a real-world setting using data from the United States Vaccine Adverse Event Reporting System (VAERS). Further, propensity score matching and disproportionality analysis was performed by calculating the adjusted reporting odds ratio (ROR) of reported ADEM cases associated with seasonal influenza vaccines using multiple logistic regression. Additionally, we analysed the time-to-onset using Weibull shape parameters (WSPs). The VAERS database contained 390,352 adverse events reported from January 2011 to December 2020. The ROR of seasonal influenza vaccines for ADEM was 3.02 (95% confidence interval: 1.72-5.33). The median duration (interquartile range) of ADEM was 11.0 (5.0-33.0) days. The median duration of ADEM induced by egg culture-based influenza vaccine (Egg-based vaccine) and cell culture-based influenza vaccine (Cell-based vaccine) was 10.0 (5.0-24.0) and 91.0 (79.0-125.0) days (P < 0.001), respectively. Only Cell-based cases had WSP β > 1, indicating a wear-out failure type. The incidence of ADEM within 30 days after administration of egg- and Cell-based vaccines was 78.6% and 0.0%, respectively. Our findings indicate that ADEM incidence is associated with seasonal influenza vaccines; thus, careful monitoring of ADEM is required within the first month of Egg-based vaccination and after two months of Cell-based vaccination. Neurologists and general practitioners should exercise caution, as the timing for careful monitoring varies depending on the vaccine type.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Cinchona bark (bark from plants of the genus Cinchona with antimalarial activity) and its alkaloid quinine were widely used to treat intermittent fevers. This paper aims to quantitatively analyze the presence of Cinchona bark, quinine and other Cinchona bark-derived substances in the Portuguese official pharmacopoeias published between 1794 and 2001. The analysis showed that the Pharmacopêa Portugueza (1876) is the Portuguese official pharmacopeia with the highest percentage of medicines containing Cinchona bark (2.61%). The Farmacopeia Portuguesa IV (1935) is the official pharmacopeia with the highest percentage of quinine-containing medicines (2.34%). Medicines made from Cinchona bark are present in the Portuguese official pharmacopoeias until the Farmacopeia Portuguesa IV (1946). Medicines made from quinine have been present in Portuguese official pharmacopoeias since the Codigo Pharmaceutico Lusitano (1835).

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death, which indicates that efficient intervention agents or strategies against HCC are urgently needed. In the present study, we firstly found that a combination of gefitinib (an ep i dermal growth factor receptor (EGFR) inhibitor) and B I 6727 (a pol o -like kinase 1 (PLK1) inhibitor) could significantly inhibit cell proliferation of HCC cells, which attenuated acquired resistance of gefitinib in HCC cells. Interestingly, our results showed that these anti-tumor effects of gefitinib in combination with BI6727 were associated with G2/M arrest. Moreover, further study revealed that BI6727 could downregulate the protein levels of cell division cycle 25C (Cdc25C) via ubiquitination-dependent pathway, which subsequently induced G2/M arrest. Furthermore, two critical checkpoints proteins ataxia telangiectasia-mutated (p-ATM)/ ATM and Rad-3 related(p-ATR) and another hallmark phosphorylated H2AX (γ-H2AX ) of DNA damage were positively regulated in HCC cells exposed to gefitinib in combination with BI6727. These results indicated that co-treatment induced G2/M arrest was closely related to DNA damage. In summary, the present study discovered that gefitinib synergizing with BI6727 could significantly facilitate DNA damage and overcome acquired resistance of HCC cells to gefitinib. Our study provides a promising approach for the combination of EGFR inhibitors and PLK1 inhibitors in the clinical treatment for HCC.

The aim of this paper is to present an overview of Dioscorides' recipes from his work De materia medica which are found in Croatian folk medicine preserved in books of folk recipes called ljekaruše. The particularities of five published and analysed Croatian books of folk recipes from the 17 th and 18 th century are examined. Recipes with drugs of herbal and animal origin, which are most often mentioned in Croatian books of folk recipes, and which were available in folk medicine at the time, are compared with those from Dioscorides' work. Many herbal drugs described in books of folk recipes are today used in contemporary phytotherapy, and modern biomedical research reveals new bioactive substances and confirms new and potential biological activities in medicinal plants used in folk medicine, which is the basis for further study of De materia medica by Dioscorides and ethnomedicinal collections. Croatian books of folk recipes are a valuable resource for multidisciplinary study, including for medicinal and pharmaceutical historians, philologists and ethnologists.

Melatonin has been shown to have an antinociceptive effect and its administration could enhance the antinociceptive effect of other drugs. This study assessed the antinociceptive effects of melatonin in combination with paracetamol and N-palmitoylethanolamide (PEA) using the formalin test in mice. Melatonin, paracetamol, and PEA were administered intraplantarly (paw) alone or combined to mice. A concentration-response curve was generated to determine the concentration needed to reach 30% of the maximal antinociceptive effect (EC₃₀). Melatonin, paracetamol and PEA induced a concentration-dependent antinociceptive effect in both phases of the formalin test, being PEA more potent (EC₃₀ = 7.4±0.2 mg/paw) than melatonin (EC₃₀ = 20.5±3.1 mg/paw) or paracetamol (EC₃₀ = 41.8±2.6 mg/paw). Combinations of melatonin with paracetamol or PEA also induced a concentration-dependent antinociceptive effect in the formalin test. Isobolographic analysis showed that melatonin interacts synergistically with either paracetamol or PEA to reduce formalin-induced inflammatory pain. However, the experimental values of EC₃₀ were significantly smaller than those calculated theoretically.

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

H/D exchange reactions can be observed by NMR spectroscopy of acebutolol (ACE). The results obtained showed deuterium incorporation at α-posi t ion of the carbonyl group of acebutolol, when using deuterium oxide or deuterated methanol as deuterium source and solvent. The spontaneous deuteration is proceeded by the following pathway CH₃→CH₂D→CHD→CD₃, through a keto-enol tautomerization reaction. Furthermore, LC-MS / QTOF analyses have confirmed the proposed H/D exchange. In order to reduce the time of total deuteration observed at the acetyl group alkaline catalysts were employed.