File Name: comparison of potency and duration of action of nalmefene and naloxone .zip
- Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action
- The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies
- Multiple Fentanyl Overdoses — New Haven, Connecticut, June 23, 2016
- Higher doses of naloxone are needed in the synthetic opioid era
Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action
Metrics details. Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary.
To date, few pharmacotherapies have been established for the treatment of alcoholism. There is a plethora of research concerning the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol. The opioid antagonist naltrexone has been found to be effective in alcohol treatment. In addition, the mu-opioid antagonist and partial kappa agonist nalmefene was recently approved by the European Medicines Agency for the treatment of alcoholism. The available literature is reviewed and discussed. Nalmefene appears to be a safe and effective treatment for alcohol dependence. In December , Selincro, containing the opioid antagonist nalmefene as the active substance, was approved by the European Medicines Agency EMA for the treatment of alcoholism.
The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies
Metrics details. There has been a dramatic increase of deaths due to illicit fentanyl. We examined the pharmacology of fentanyl and reviewed data on the number of repeat doses of naloxone used to treat fentanyl overdoses. Multiple sequential doses of naloxone have been required in a certain percentage of opioid overdoses due to fentanyl. In addition, fentanyl appears to differ from other opioids as having a very rapid onset with high systemic levels found in overdose victims. A rapid competition is required by naloxone to out-compete large numbers of opioid receptors occupied by fentanyl in the CNS. Taken together, we propose that higher doses of naloxone are needed to combat the new era of overdoses due to the more potent synthetic opioids such as fentanyl.
Serum concentration of naloxone at 5 minutes was 1. Their serum half-lives from one to four hours were approximately the same, minutes. With naloxone, the brain-serum concentration ratios ranged from 2. Concentration of naloxone in the brain declined parallel to that in the serum. However, with morphine the initial brain concentration was approximately one tenth that in the serum 0.
As opioids have become more common in clinical practice for the treatment of both acute and chronic pain, so too has the need for a deeper understanding of the clinical applications of opioid antagonists. The purpose of this review is to present both the longstanding and potential new indications for the use of drugs that block the effects of opioid receptors. There is a growing body of data demonstrating the modulation of pain by opioid antagonists. We briefly discuss the well-established role that these agents play in the reversal of life-threatening opioid toxicity and explore both existing and expanding clinical applications, including their apparent paradox that they may themselves be associated with analgesia. This is a preview of subscription content, access via your institution. Rent this article via DeepDyve. How reliable is pain as the fifth vital sign?
COMPARISON OF POTENCY AND DURATION OF ACTION OF NALMEFENE AND NALOXONE · Article PDF first page preview · Citing articles via · Most Viewed.
Multiple Fentanyl Overdoses — New Haven, Connecticut, June 23, 2016
Opioids are substances that, when reaching opioid receptors , have effects similar to those of morphine. Side effects of opioids may include itchiness , sedation , nausea , respiratory depression , constipation , and euphoria. Long-term use can cause tolerance , meaning that increased doses are required to achieve the same effect, and physical dependence , meaning that abruptly discontinuing the drug leads to unpleasant withdrawal symptoms.
Higher doses of naloxone are needed in the synthetic opioid era