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Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Another lidocaine-related antiarrhythmic medication that is structurally similar to encainide and procainamide, Flecainide has not been studied in human pregnancy. According the manufacturer, Flecainide is associated with an increased incidence of birth defects and embryotoxic effects in certain strains of rabbits given four times the usual human therapeutic dose. However, congenital anomalies were not increased in frequency in rats, mice, and other strains of rabbits given in the usual human dose (Manufacturer insert). A case report suggested an association with birth defects with flecainide. Flecainide has been used to treat fetal arrhythmias, but fetal deaths have occurred with this treatment. Efficacious alternative but related medications available with a better safety profile are available. Thus, flecainide should be avoided, or at least used only as the drug of last resort when others have failed. It is an old FDA category C drug.
Antibiotics: The Need for Innovation
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The adaptive ability for bacteria to develop resistance is of great concern. A large proportion of Streptococcus pneumoniae and Staphylococcus aureus strains are resistant to β-lactam antibiotics. More ominously, resistance is even rising against the drug of last resort for treating MRSA, vancomycin. Hence, it is imperative that medicinal chemist continue to develop drugs to combat infection. Bacteria can acquire resistance against many antibiotics and this is known as multi-drug resistance. Multi-drug resistance can be acquired by the accumulation of multiple genes, each of which codes for resistance against an individual drug, typically on resistance plasmids within the cell. Multi-drug resistance can also occur from over expression of multidrug efflux pumps, enabling many types of antibiotic to be extruded from the bacterial cell. Some gram-negative bacterial strains are resistant to all known antibiotics, notably those belonging to Pseudomonas aeruginosa and Acinetobacter baumanii, and can serve as a reservoir for transmission of resistant genes. The emergence of so-called ‘pan-resistant’ bacteria coincides with a regression in novel drug development by major pharmaceutical companies, as the economic incentive to produce antibiotics is low compared to other drugs, such as anti-cancer agents. Society without these lines of defence to combat infection is a sombre thought.
Complications of Antibiotic Therapy
Published in Stephen M. Cohn, Matthew O. Dolich, Complications in Surgery and Trauma, 2014
Mohamed Fahim, Chad M. Thorson, Nicholas Namias
Colistimethate has emerged as a drug of last resort for Acinetobacter baumannii infections for multidrug-resistant isolates. It has been used both intravenously and inhalationally. Intravenous administration is associated with reversible, dose-dependent nephrotoxicity. Neurologic side effects ranging from not uncommon paresthesias to rare neuromuscular blockade have been reported. Inhalational therapy is generally well tolerated.47,48
In vitro and in vivo activity of meropenem+avibactam against MBL-producing carbapenem-resistant Klebsiella pneumoniae
Published in Expert Review of Anti-infective Therapy, 2023
Xiuyun Li, Zhaowen Chen, Jin Jiao, Shifu Wang, Yuehua Wang, Weiwei Wu, Huijun Yang, Hongxiang Lou
The emergence of bacterial resistance threatens the clinical usefulness of antibiotics and creates a serious global public health situation [1,2]. Klebsiella pneumoniae (K. pneumoniae) is a common cause of antimicrobial-resistant opportunistic infections in hospitalized patients. It is naturally resistant to penicillins, and its members often carry acquired resistance to multiple antimicrobials [3]. Carbapenems are often the drugs of last resort to control multi-drug resistant (MDR) K. pneumoniae infections. In recent years, with the widespread use of carbapenems, carbapenem resistant K. pneumoniae (CRKP) strains have gradually emerged and become widely popular. The production of carbapenemases, mainly K. pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs), is closely related to the resistance of K. pneumoniae to carbapenems [4,5]. CRKP often develops resistance to multiple antibacterial agents at the same time, and treating the infections caused by CRKP poses a huge challenge due to limited treatment options. Hence, CRKP is responsible for significant morbidity, mortality, and excess healthcare costs [4,6]. Thus, CRKP strains are considered to be an urgent public health threat of international concern and has been a research focus, requiring new therapies for these organisms.
The clozapine to norclozapine ratio: a narrative review of the clinical utility to minimize metabolic risk and enhance clozapine efficacy
Published in Expert Opinion on Drug Safety, 2020
Kenya A. Costa-Dookhan, Sri Mahavir Agarwal, Araba Chintoh, Veronica N. Tran, Nicolette Stogios, Bjørn H. Ebdrup, Sanjeev Sockalingam, Tarek K. Rajji, Gary J. Remington, Dan Siskind, Margaret K. Hahn
To summarize, clozapine has clear superior clinical efficacy in reducing positive symptoms in treatment-refractory schizophrenia and is often the drug of last resort for many patients. Hence, any strategy that can help improve its effects, and potentially reduce side effects needs to be explored in detail. The CLZ:NDMC ratio represents one such parameter that can influence clinical outcomes and is available for pharmacological manipulation. Ultimately, the CLZ:NDMC ratio could have potential utility for monitoring, and treatment enhancement, and future work should examine the utility of manipulating the ratio to improve individual patient outcomes.
Trends in molecular diagnostics: 12th European Meeting on Molecular Diagnostics, Noordwijk aan Zee, the Netherlands, 12-14 October 2022
Published in Expert Review of Molecular Diagnostics, 2023
Anne J.M. Loonen, Rob Schuurman, Adriaan J.C. van den Brule
The meeting started with a session dedicated to molecular diagnostics in oncology. Important topics such as comprehensive mutation profiling by WGS and methylation profiling of tumors were addressed. Paul Roepman (Hartwich Medical Foundation, Amsterdam, The Netherlands) elaborated on the role of WGS in cancer diagnostics and therapy prediction. In current molecular pathology, diagnostic tests (part of standard of care) only cover a small fraction of the genomic changes that can occur in tumor cells and often are performed in an iterative way. WGS generates a more complete picture of the genomic characteristics of a tumor in a single test, saving valuable tissue sample and patient time and helps with ‘first time right’ treatment decisions. ‘Precision oncology’ can help select the best suitable treatment at the right time. Roepman also discussed cost-effectiveness and the clinical utility of WGS. WGS can be most impactful in 1) patients with cancer of unknown primary tumor, 2) cases with complex biomarkers or gene signatures, and 3) clinical studies with drugs of last resort. WGS has many advantages; however, an important drawback is the lack of information on methylation status. David Capper (Charité – Universitätsmedizin, Berlin, Germany) addressed the value of DNA methylation profiling in oncology diagnostics with a focus on tumor types of the central nervous system (CNS). Capper showed a comprehensive approach for the DNA methylation-based classification of CNS tumors and demonstrated its application in a routine diagnostic setting. For broader accessibility, a free online classifier tool was designed. He showed a blueprint for the generation of machine-learning-based tumor classifiers across other cancer entities, with the potential to fundamentally transform tumor pathology.