Naloxone in opioid poisoning: walking the tightrope

Clarke, Simon; Dargan, Paul I.; Jones, Alison L

doi:10.1136/emj.2003.009613

Cited by 171 publications

(142 citation statements)

References 73 publications

(40 reference statements)

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“…However, this dose is typically used to antagonize opioid induced respiratory depression, an effect predominantly mediated by the central nervous system, and may not be high enough to block the effects of endogenous opioids in opioid naive subjects. Indeed infusions of up to 4 mg/kg/hr are reportedly well tolerated in healthy humans, although sensitivity to rectal distension at high doses is yet to be investigated (Clarke et al, 2005). Interestingly, our results suggest monocyte / macrophage derived β-endorphin levels do not differ between IBS patient cohorts, indicating the differences in the functional effects that supernatants from IBS-D and IBS-C patients have on colo-rectal sensory afferents are due to excitatory actions of cytokines TNF-α, IL-1β and IL-6, which we previously showed were increased in IBS-D relative to IBS-C (Hughes et al, 2013a;Liebregts et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients, Brain, Behavior, and Immunity (2014), doi: http://dx.doi.org/10. 1016/j.bbi.2014.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-endorphin was identified predominantly in monocyte / macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in µ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte / macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

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Section: Discussionmentioning

confidence: 99%

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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“…Airway support and restoration of breathing are essential before proceeding with pharmacological intervention [14,15]. Once the airway is secured, administration of an opioid antagonist is the next step to reverse opioid toxicity.…”

Section: Managementmentioning

confidence: 99%

“…Both studies pointed out that the IM and SC routes provide erratic absorption and delayed elimination [18,19]. However, these routes are acceptable alternatives when the IV route is not readily accessible [11,14,16]. A 2009 study by Kerr et al demonstrated that time to adequate response was comparable between IN and IM naloxone [20].…”

Section: Managementmentioning

confidence: 99%

Use of naloxone for the management of opioid overdose

guyen¹

2012

iosrphr

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Abstract--Opioid overdose is a potentially life-threatening condition that requires immediate medical attention, often landing affected individuals into the emergency department. The longstanding treatment for opioid overdose has been naloxone, a pure opioid antagonist that reverses all signs of opioid intoxication. While effective as a reversal agent, naloxone has a half-life which is shorter than all opioids. Once the effect of naloxone wears off, patients may experience recurrence of opioid intoxication and the consequences can be fatal. The objective of this article is to review the available literature that addresses routes of administration and doses of naloxone as well as the necessary duration of observation when treating patients who present with opioid overdose. The preferred route of administration remains intravenous with intramuscular and intranasal considered alternatives. Recommended dosing is dependent upon history and the opioid being reversed; however, doses range from 0.05 -2 milligrams. A literature search revealed a relatively small number of studies related to observation periods following naloxone administration and subsequent recurrence of opioid toxicity. The available literature supports incorporation of a two-hour observation period following administration of naloxone for short-acting opioids and a longer four to six hour observation period for reversal of long-acting opioids.

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“…70,71 Currently, it is common practice for paramedics to use naloxone in most EMS systems. Prescription naloxone is considered an off label use of the drug.…”

Section: Legalities Of a Naloxone Prescription Programmentioning

confidence: 99%