Articles: narcotic-antagonists.
-
Eur. J. Clin. Pharmacol. · Dec 2018
Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil.
Pharmacodynamic studies of naloxone require opioid agonism. Steady state condition may be achieved by remifentanil TCI (target controlled infusion). Opioid agonism can be measured by pupillometry. It is not known whether there are arteriovenous concentration differences for naloxone. The aim was thus to further develop a model for studying pharmacokinetic/pharmacodynamic aspects of naloxone and to explore whether a significant arteriovenous concentration difference for naloxone in humans was present. ⋯ Onset of reversal by IV naloxone was rapid and lasted 118 min. The minimum effective concentration was 0.5 ng/ml. Using TCI remifentanil to obtain a steady-state opioid agonism may be a useful tool to compare new naloxone products.
-
Despite rising rates of opioid overdose in the United States, few studies have examined the frequency of non-fatal overdose events or mortality outcomes following resuscitation. Given the widespread use of naloxone to respond to overdose-related deaths, naloxone administration may provide a useful marker of overdose events to identify high-risk users at heightened risk of mortality. We used naloxone administration by emergency medical services as a proxy measure of non-fatal overdose to examine repeat events and mortality outcomes during a 6-year period. ⋯ Among US emergency medical service patients administered naloxone for opioid overdose, those with repeat non-fatal opioid overdose events are at a much higher risk of mortality, particularly drug-related mortality, than those without repeat events.
-
Opioid receptors are distributed throughout the central and peripheral nervous systems and on many nonneuronal cells. Therefore, opioid administration induces effects beyond analgesia. In the enteric nervous system (ENS), stimulation of µ-opioid receptors triggers several inhibitory responses that can culminate in opioid-induced bowel dysfunction (OBD) and its most common side effect, opioid-induced constipation (OIC). ⋯ Although questions of cost-effectiveness and relative efficacy versus laxatives remain, PAMORAs can mitigate OIC and improve patient QOL. PAMORAS may also have applications beyond OIC, including reducing the increased cardiac risk or potential tumorigenic effects of opioids. This review discusses the burden of OIC and OBD, reviews the mechanism of action of new OIC therapies, and highlights other potential opioid-related side effects mediated by peripheral opioid receptors in the context of new OIC therapies.
-
Randomized Controlled Trial
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.
In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. ⋯ The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.