Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · Jan 2015
ReviewBiomarkers of drug-induced acute kidney injury in the adult.
This article addresses general biomarkers of drug-induced acute kidney injury (AKI) and their application in development and progression of AKI in the adult. It also highlights some clinical benefits, but also uncertainties, of biomarker use. ⋯ Traditional parameters, such as SCr, provide some guidance for functional decline in drug-induced AKI but early, more sensitive, affordable, clinically acceptable, biomarkers of kidney dysfunction are needed. Basic biological understanding of AKI will improve with high-throughput methodologies such as proteomics and metabolomics, and this should lead to identification and usage of novel biomarkers. Ultimately, a combination of biomarkers indicating kidney dysfunction and damage is likely to be required.
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Expert Opin Drug Metab Toxicol · Jan 2015
ReviewManagement of pulmonary toxicity associated with targeted anticancer therapies.
Targeted anticancer therapies act by interfering with defined molecular entities and/or biologic pathways. Because of their more specific mechanism of action, adverse events (AEs) on healthy tissues are intended to be minimal, resulting in a different toxicity profile from that observed with conventional cytotoxic chemotherapy. Pulmonary AEs are rare but potentially life-threatening and it is, therefore, critical to recognize early on and manage appropriately. ⋯ Novel agents used in the treatment of cancer have specific side-effects, the result of allergic reactions, on-target and off-target effects. Clinical syndromes associated with pulmonary toxicity vary from bronchospasms, hypersensitivity reactions, pneumonitis, acute respiratory distress, lung bleeding, pleural effusion to pneumothorax. Knowledge of risk factors, a high index of suspicion and a complete diagnostic work-up are essential for limiting the risk of these events becoming life threatening. The development of treatment algorithms is extremely helpful in managing these events. It is probable that these toxicities will be even more frequent with the introduction of combination therapies with the obvious challenge of discerning the responsible agent.
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Clinicians use antiemetic drugs in a multitude of scenarios. Despite the differences in subspecialty and etiology of the nausea, practitioners of all subspecialties use the same drugs in similar ways to provide relief for their patients. ⋯ The key to providing relief for patients suffering from nausea and vomiting is to consider multiple drugs to approach the nausea in a systematic way. Anesthesiologists identify patients who are at high risk of nausea and vomiting based on physical characteristics and surgical procedures. Oncologists treat nausea based on the prescribed chemotherapeutics regimen and known risk of emesis while palliative care physicians and others balance the etiology of the nausea while optimizing patients other co morbid conditions.
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Expert Opin Drug Metab Toxicol · Oct 2014
ReviewADMET considerations when prescribing novel therapeutics to treat restless legs syndrome.
Restless legs syndrome (RLS) is a commonly occurring sensory motor disorder that might impair nocturnal rest causing decreased alertness, depression, reduced job performance and poor quality of life. In patients affected by severe RLS, a pharmacological treatment is mandatory. ⋯ The drugs currently available for RLS treatment do not always provide an optimal control of symptoms. There is still need for effective and well-tolerated new drugs. Long-acting dopamine agonists showed better efficacy than short-acting compounds in the treatment of severe RLS. There seems to be an inverse relationship between the half-life of the compound and the development of augmentation. Monoamine oxidase B inhibitors could be good candidates for initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS insufficiently treated with first-line drugs and could be used as a long-term treatment in severe RLS when alternative satisfactory drug regimens are unavailable.
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Expert Opin Drug Metab Toxicol · Aug 2014
ReviewTailored tools to improve pharmacotherapy in infants.
Extensive within-population variability is the essence of neonatal pharmacology. Despite this, infants remain one of the last therapeutic orphans. Together with additional legal initiatives, tailoring of already available tools (modeling, covariates, pharmacovigilance) may significantly improve pharmacotherapy in infants. ⋯ Knowledge on pharmacotherapy in infants is lagging. Tailoring available tools to the specific characteristics (maturation) and clinical needs (newly emerging covariates) of infants is feasible but needs creativity and a multidisciplinary collaboration between modelers, academia, clinical researchers and, obviously, the public, including parents.