Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Jul 2013
ReviewDimethyl fumarate (BG-12) for the treatment of multiple sclerosis.
Treatments for multiple sclerosis (MS) are only partially effective and most require a parenteral route of administration and/or may have severe side effects. Dimethyl fumarate is the active compound of BG-12 recently licensed for the treatment of relapsing-remitting MS. The pivotal Phase III trials have demonstrated an approximately 50% reduction of relapse rates compared with placebo paralleled by a reduction in new lesion formation on MRI. ⋯ Severe side effects were not more common than in the placebo group for a treatment period of 2 years. The mode of action is not exactly clear and both immunomodulatory effects and an activation of the transcription factor Nrf2 are suggested. This new oral drug will be a welcome addition to existing MS treatments.
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Expert Rev Clin Pharmacol · Nov 2012
ReviewBiomarkers as predictors of outcome after cardiac arrest.
Cardiac arrest (CA) is a major health and economic problem. Management of patients resuscitated from CA is challenging for clinicians, and the mortality rate of those who achieve return of spontaneous circulation remains high. Hypoxic brain injury, cardiovascular abnormalities and systemic ischemia/reperfusion response characterize the so-called 'postcardiac arrest syndrome', which could lead to multiple organ failure and poor outcome after CA. ⋯ A number of factors are thought to influence the prognosis of patients after CA, but due to the heterogeneity of CA population and scenarios no single factor has been identified as a reliable predictor of outcome and the timing and optimal approach to prognostication is still controversial. Biomarkers represent a growing area of interest in this field, as they may provide clinicians with early information on the severity of organ dysfunction to make a decision on clinical strategies and prognosticate outcome. In this article, the authors will focus on cardiac, neurological and inflammatory biomarkers as potential predictors of outcome after CA.
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Expert Rev Clin Pharmacol · Jul 2012
ReviewPredicting ICU admission in community-acquired pneumonia: clinical scores and biomarkers.
Community-acquired pneumonia (CAP) remains a common and serious worldwide health problem. Despite all the advances in therapy, significant interest has focused on the identification of patients with CAP who require intensive care unit admission to improve their outcomes. The severity assessment of CAP provides an important guide to clinicians in deciding the site of care and the use of empiric antibiotics and adjuvant therapy. ⋯ An objective scoring system with a high level of sensitivity and specificity to predict the severity of CAP and the need for high levels of care do not exist. Today, the addition of clinical scores and biomarkers to clinical judgment is the best approach to optimize the care of severe CAP. Future research will allow validation of these and newer tools to improve the prognosis of patients with CAP.
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Expert Rev Clin Pharmacol · Jul 2012
ReviewIntravenous lipid administration for drug-induced toxicity: a critical review of the existing data.
Following the discovery that administration of intravenous lipid emulsion (ILE) may reverse the cardiac and neurological toxicity of certain local anesthetic agents, ILE's potential role has recently been explored in the setting of toxicity attributed to a variety of different drugs. The potential mechanisms, safety and efficacy of this approach are considered in this review. ⋯ Administration has typically involved bolus administration followed by continuous maintenance infusion, and a number of different mechanisms are proposed, from preferential partitioning of the drug from cardiac tissue to the circulating lipid fraction and direct inotropic effects related to carnitine pathways and fatty acid oxidative metabolism. No major adverse effects have been encountered, but too few data exist to adequately address the safety profile of ILE.
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Expert Rev Clin Pharmacol · May 2012
ReviewCriteria for acetylcysteine treatment and clinical outcomes after paracetamol poisoning.
Acetylcysteine is an effective antidote for paracetamol (acetaminophen) poisoning, but different treatment criteria exist internationally. In the UK, acetylcysteine is indicated by paracetamol concentrations higher than the Prescott nomogram or higher than 50% of the nomogram in patients with increased susceptibility to liver toxicity. In the USA, a single '150-line' nomogram has been used that removes the need for additional clinical risk assessment. ⋯ An existing database of 1191 patients admitted to hospital after paracetamol overdose identified that the 4-h equivalent paracetamol concentration was: ≥200 mg/l in 163 patients (15.6%; 95% CI: 13.3-18.2%), ≥150 mg/l in 264 (24.3%; 95% CI: 21.5-27.5%) and ≥100 mg/l in 426 patients (39.3%; 95% CI: 35.6-43.2%), and acute liver injury occurred in 3.7% (95% CI: 1.4-8.0%), 2.3% (95% CI: 0.8-5.0%) and 1.9% (95% CI: 0.8-3.7%), respectively. The different indications for acetylcysteine used by the UK and USA would result in similar numbers of patients treated, although the criteria would define patients with different characteristics and patterns of overdose. The relative merit of these different international approaches to acetylcysteine administration is considered in this article.