Terry W Smith

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Opioid treatment of pain is generally safe with 0.5% or less events from respiratory depression. However, fatalities are regularly reported. The only treatment currently available to reverse opioid respiratory depression is by naloxone infusion. The efficacy of naloxone depends on its own pharmacological characteristics and on those (including receptor(More)
Opioids induce respiratory depression via activation of μ-opioid receptors at specific sites in the central nervous system including the pre-Bötzinger complex, a respiratory rhythm generating area in the pons. Full opioid agonists like morphine and fentanyl affect breathing with onset and offset profiles that are primarily determined by opioid transfer to(More)
Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of(More)
Morphine is the first choice of treatment of severe post-operative pain, despite the occurrence of often discomforting (post-operative nausea or vomiting (PONV)) and sometimes dangerous (sedation, respiratory depression) side effects. Literature data indicate that morphine's active metabolite, morphine-6-glucuronide (M6G), is a powerful analgesic with a(More)
IMPORTANCE OF THE FIELD Worldwide the number of patients affected by chronic pain is growing and conventional treatment is often insufficient. Recently the importance of the N-methyl-d-aspartate receptor (NMDAR) in the mechanisms and maintenance of chronic pain was established. Ketamine (introduced in the 1960s as an anesthetic) is the most studied NMDAR(More)
AIMS The aim of the study was to assess analgesia and safety effects of a range of intravenous doses of M6G (10, 20 and 30 mg/70 kg), compared to placebo, in postoperative patients. METHODS In a randomized, multicentre, double-blind study, patients undergoing knee replacement surgery under spinal anaesthesia were administered one of three doses of M6G, or(More)
Morphine-6-glucuronide (M6G) is morphine's active metabolite acting at the mu-opioid receptor. Recent experimental human studies and 5 of 6 randomized clinical trials indicate that M6G causes adequate and long lasting pain relief comparable to morphine. There are various observations that M6G is associated with a reduction in the severity of side effects(More)
1261 June 2013 Drug-induced Respiratory Depressidon and Ampakines MANY of the drugs used currently by anesthesiologists produce serious side effects, of which respiratory depression is one that is potentially fatal. Although we know that anesthetics and opioids are relatively safe in the hands of anesthesiologists and other well-trained anesthesia(More)
BACKGROUND In pharmacokinetic-pharmacodynamic modeling studies, venous plasma samples are sometimes used to derive pharmacodynamic model parameters. In the current study the extent of arteriovenous concentration differences of morphine-6-glucuronide (M6G) was quantified. We used simulation studies to estimate possible biases in pharmacodynamic model(More)
OBJECTIVES To determine the dose-response effect of intravenous morphine-6-glucuronide (M6G) on acute postoperative pain. METHODS Patients undergoing knee replacement surgery under spinal anesthesia were randomly assigned to 1 of 4 single intravenous M6G doses, 0 (placebo), 10, 20, or 30 mg/70 kg, administered 150 minutes after the spinal anesthetic was(More)
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