Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Feb 2015
EditorialPharmacological treatment of pain: future trends and novel insights.
The pharmacological treatment of chronic pain is generally hampered by a limited clinical outcome. Hence, there is a strong need for new therapeutic concepts considering the identification of novel targets and related drugs, but also optimization of established therapeutic regimes through individualization. In this issue, focused on "Pain," we discuss some of the recent new concepts in pain treatment, understanding of pain heterogeneity, and subsequent optimization of analgesic treatment, but also novel insights into interactions of nonopioids.
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Clin. Pharmacol. Ther. · Feb 2015
ReviewNocebo vs. placebo: the challenges of trial design in analgesia research.
The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments that directly target biological mechanisms. The shortcomings of randomized clinical trials are currently discussed along with potential improvements of trial designs. ⋯ We present three major challenges in randomized clinical trials: (i) increasing placebo effects, (ii) variability of the placebo effect, and (iii) risk of un-blinding. We then explain how recent placebo and nocebo studies of effects of verbal suggestion, expectancy, and emotions may improve understanding and discussion of increasing placebo effects, account/control for large parts of the variability of placebo effects, and suggest ways to improve blinding in future trials.
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For opioids requiring CYP2D6 O-demethylation to active metabolites, poor metabolizers have reduced metabolite formation and minimal pain reduction. Clinically, this has only reliably been shown for tramadol. ⋯ In Asian populations, the high OPRM1 118A>G frequency associates with higher opioid dosage requirements. Clinical translation of opioid genetics is premature because many important pain and addiction phenotype factors contribute.
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Clin. Pharmacol. Ther. · Feb 2015
Opioids for chronic noncancer pain: still no evidence for superiority of sustained-release opioids.
Opioids are controversial in the treatment of chronic pain due to the risk of addiction, misuse, and death. Long-acting formulations of opioids have been hypothesized to improve pain relief, sleep quality, and lower the risk of side effects and addiction compared to short-acting formulations of opioids. Thus, several guidelines have recommended the use of long-acting opioid formulations over short-acting ones in the treatment of chronic noncancer pain. However, is there really evidence of their superiority?
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Clin. Pharmacol. Ther. · Feb 2015
Clinical TrialOndansetron pharmacokinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome.
Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). The pharmacokinetics of ondansetron have not been characterized in pregnant women or in newborns. ⋯ A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.