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Introduction
Published in Peri J. Ballantyne, Kath Ryan, Living Pharmaceutical Lives, 2021
Pharmaceuticals have other properties that complicate users’ experiences of them, and that have helped to construct a particular lay knowledge of pharmaceuticals as potentially ‘remedy and poison’ (Martin, 2006). While pharmaceuticals are consumed with the intention to benefit the user’s physical or mental health status – they can and do produce both intended and unintended effects. That is, while drugs are marketed on the basis of evidence from clinical trials illustrating their primary benefit for some intended application, they may also produce unintended ‘side’ effects. Identification of these (intended and unintended) effects is part of the calculus of receiving a license to market a new pharmaceutical product. That is, a manufacturer is required to adhere to rules to document and report (intended and) unintended effects and to duly inform the future user of them (Abraham, 2008; Lexchin, 2013). Yet, a body of research on idiosyncratic drug reactions illustrates that pharmaceutical effects may be non-specific and unanticipated (i.e., see Kaplowitz, 2005; Uetrecht, 2008). Another issue – focused on the so-called ‘off-label’ uses of licensed pharmaceuticals – reveals and makes problematic the autonomy given health care professionals to experiment with pharmaceuticals for conditions that have not undergone trials for specific clinical applications (Stafford, 2008), and whose impacts have not been systematically evaluated. All of this is part of the context in which the public accesses and negotiates the use of medicines.
Acute liver failure
Published in Louisa Baxter, Neel Sharma, Ian Mann, The Junior Doctor’s Guide to Gastroenterology, 2018
Louisa Baxter, Neel Sharma, Ian Mann, Ian Sanderson
Drugs (e.g. paracetamol). This is the commonest cause of liver failure in the UK. Ingestion of > 10 g paracetamol/24 hours, and of smaller doses in patients with alcoholic liver disease, may be hepatotoxic. Hepatotoxic drug effects may be dose related (those that will occur in most patients given a sufficiently high dose) or idiosyncratic drug reactions (unusual or unpredictable reactions), which usually occur within 6 months of starting the medication. As paracetamol is such a common aetiological factor, you should be familiar with the features of severe paracetamol toxicity, which are as follows:
Unilateral Idiopathic Choroidal Effusion in a Patient Who Takes Sulfonamides
Published in Ocular Immunology and Inflammation, 2021
All in all, malignances presenting with choroidal effusion are rare. However, in the case of choroidal effusion, neoplasm has to be one of the top listed differentials, especially if it is unilateral and patient has not had any previous eye surgery. Nowadays, we have options for multimodal imaging which may be quite helpful in making suspicion on malignant process, although clinical picture or history are not in favor of that. As soon as a definite diagnosis is made, treatment may be started. Eventually, our case did not show the presence of malignant process and we were able to diagnose it as idiopathic unilateral choroidal effusion which should be diagnosed only if all other options are excluded. At the same time, the suprachoroid drainage was a diagnostic and treatment procedure. The only other thing to consider is whether the choroidal effusion was conceivably caused by an idiosyncratic drug reaction. We do know that Topiramate can cause a secondary angle closure glaucoma, presumably as a result of choroidal effusions arising as a result of disruption of the blood-retinal barrier.4 A similar drug-related mechanism is conceivable in our patient, but the finding against this is the unilateral nature of the disease.
Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development
Published in Drug Metabolism Reviews, 2021
Several in silico, in vitro, and in vivo methods have been used to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of drugs at the early stage of drug development to better inform molecular design, as well as the elimination of drug candidates with low chances of success. A major safety issue that can contribute to the termination of drug development programs is idiosyncratic drug reactions such as drug-induced liver injury (DILI) and drug-induced kidney injury (DIKI). Toxicogenomic analyses of DILI can facilitate the preclinical identification of hepatotoxicity and its underlying mechanisms. In the paper titled ‘Toxicogenomics of drug induced liver injury – from mechanistic understanding to early prediction,’ Lauschke provided a comprehensive overview of toxicogenomic studies across human liver culture models and demonstrates that toxicogenomic analyses of stem cell-derived organoids and primary human hepatocytes in complex 3 D microtissues has the potential to identify complex individual risk factors with the overall goal of improving preclinical safety studies. Similarly, Kulkarni discussed the mechanisms of DIKI, and non-clinical models that can be used for early prediction of DIKI in the paper titled ‘Methods in the Prediction of Drug-Induced Kidney Injury.’
Adjunctive cenobamate for the treatment of focal onset seizures in adults with epilepsy: a critical review
Published in Expert Review of Neurotherapeutics, 2020
Skin reactions and immune-mediated hypersensitivity reactions are idiosyncratic adverse events commonly associated with ASMs and are generally mild in severity [40]. Drug reaction with eosinophilia and systemic symptoms (DRESS) and other more severe adverse events, however, are of major concern. Although very rare, they can be life-threatening; in addition, those that are not fatal may result in treatment discontinuation [40]. Prevention of these types of drug reactions is of the utmost importance when developing a new ASM, and is accomplished through vigilant monitoring and management during clinical trials and treatment. It has previously been shown that serious adverse events from idiosyncratic drug reactions with ASMs can be minimized through knowledge of risk factors, avoidance of certain ASMs in subpopulations who may be at risk, monitoring of clinical response, and cautious dose titration [40].