Clinical pharmacology and therapeutics
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Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.
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Clin. Pharmacol. Ther. · Oct 2014
Antipsychotics and associated risk of out-of-hospital cardiac arrest.
Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. ⋯ Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30).
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Clin. Pharmacol. Ther. · Oct 2014
Clinical TrialPulmonary penetration of piperacillin and tazobactam in critically ill patients.
Pulmonary infections in critically ill patients are common and are associated with high morbidity and mortality. Piperacillin-tazobactam is a frequently used therapy in critically ill patients with pulmonary infection. Antibiotic concentrations in the lung reflect target-site antibiotic concentrations in patients with pneumonia. ⋯ The median piperacillin and tazobactam pulmonary penetration ratios were 49.3 and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentrations were unpredictable and negatively correlated with pulmonary permeability. Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam-susceptible organisms in some critically ill patients.
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Clin. Pharmacol. Ther. · Aug 2014
ReviewLack of drug dosing guidelines for critically ill patients receiving continuous renal replacement therapy.
Acute kidney injury requiring continuous renal replacement therapy is common, costly, and associated with mortality rates of up to 60%. Accurate pharmacokinetic data are essential to developing rational individualized dosing strategies and providing optimal care to these patients, yet few such data exist, probably due in part to an absence of regulatory guidance on the issue. The Kidney Health Initiative is working with stakeholders to propose strategies to address this in a standardized manner.
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Clin. Pharmacol. Ther. · Jul 2014
ReviewWarfarin pharmacogenetics: to genotype or not to genotype, that is the question.
Genotype is well recognized to influence the dose of warfarin necessary for therapeutic anticoagulation. Recent randomized controlled trials evaluating the clinical utility of genotype-guided warfarin dosing have produced varying results. We review the design and results of the recent clinical trials, assess the impact of their findings on warfarin dosing, and examine unanswered questions related to clinical implementation of warfarin pharmacogenetics.