Hydromorphone-3-glucuronide: Biochemical synthesis and preliminary pharmacological evaluation

Wright, Andrew; Nocente, Mary-Louise; Smith, Maree T.

doi:10.1016/s0024-3205(98)00288-4

Cited by 50 publications

(29 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…M-6-G is an opioid receptor agonist and potent analgesic, whereas M-3-G has poor affinity for opioid receptors [80] and therefore lacks analgesic potency [44]. Animal studies have suggested a neuroexcitatory role associated with the 3-glucuronide metabolites of morphine and hydromorphone [5,96,97,110]. A study of cancer patients found no correlation between cognitive impairment and the morphine-6-glucuronide-to-morphine ratio [101].…”

Section: Fluid Deficit State: Pathophysiology and Pathogenesismentioning

confidence: 99%

Delirium and dehydration: some fluid for thought?

Lawlor

2002

Support Care Cancer

View full text Add to dashboard Cite

Delirium is a frequent complication of advanced cancer. It is characterized by cognitive deficits and behavioral disturbance, and therefore can potentially result in severe symptom distress and impeded communication between patient and family and between patient and medical staff. The reversibility of delirium depends on its underlying causes. Delirium is multifactorial in origin, and precipitating or contributory factors include dehydration and hypovolemia. Much of the debate concerning the role of hydration in advanced cancer has centered on symptoms such as thirst, and ethical issues such as parenteral hydration and its association with prolongation of life, with the association between hydration status and delirium largely excluded. This review examines the latter association in the light of recent studies. It also provides an outline of relevant pathophysiology and clinical assessment, a decision-making framework and a practical approach to the techniques of assisting hydration. This will hopefully help physicians and families in weighing up the merits of assisted hydration in an individual context and help them to achieve a consensus on the role of hydration that is consistent with the goals of care.

show abstract

Section: Fluid Deficit State: Pathophysiology and Pathogenesismentioning

confidence: 99%

Delirium and dehydration: some fluid for thought?

Lawlor

2002

Support Care Cancer

View full text Add to dashboard Cite

show abstract

“…allodynia, myoclonic jerks, and seizures) in patients who received large doses of systemically administered MOR [1][2][3][4][5]. M3G has been reported to have neuroexcitatory action [10][11][12][13][14][15][16], and this neuroexcitatory action of M3G reduces analgesia of MOR and M6G [17]. Moreover, in cultured hippocampal neurons it was reported that M3G indirectly activates the NMDA receptor resulting in increased cytosol calcium concentrations via a predominantly non-opioidergic mechanism [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…[8,9]. On the other hand, M3G has neuroexcitatory action and does not show an analgesic effect [10][11][12][13][14][15][16]. M3G evokes dose-dependent behavioural excitation when administered directly into the lateral ventricle of the adult male SpragueDawley rat brain [14].…”

Section: Introductionmentioning

confidence: 99%

Relationship between plasma concentrations of morphine and its metabolites and pain in cancer patients

et al. 2010

View full text Add to dashboard Cite

show abstract

“…81 The equianalgesic dose ratio of oral to parenteral morphine in single dose studies is 6 to 1, but in chronic oral dosing, this ratio changes to between 2 and 3 to 1, possibly related to enterohepatic circulation, which could facilitate an accumulation of M-6-G. 82 Animal studies have demonstrated the induction of a neuroexcitatory state with M-3-G, 83 normorphine-3-glucuronide, 84 and also with the hydromorphone metabolite, hydromorphone-3-glucuronide. 85 Opioid-induced neurotoxicity including cognitive dysfunction has been reported in the case of methadone, 86 which has no known active metabolites, and in the case of an acute overdose of fentanyl, 87 in which its temporal occurrence was likely to be inconsistent with a metabolite role in causation. Studies examining the correlation between the level of parent opioid or its metabolites and the level of cognitive deficit during opioid treatment have revealed some conflicting results.…”

Section: Pathophysiology Of Opioid-associated Cognitive Dysfunctionmentioning

confidence: 99%

The panorama of opioid‐related cognitive dysfunction in patients with cancer

Lawlor

2002

Cancer

105

View full text Add to dashboard Cite

BACKGROUNDOpioids have an essential role in the management of pain in cancer patients, particularly those with advanced disease. Cognitive dysfunction is a recognized complication of opioid use. However, misconceptions and controversy surround the nature and prevalence of its occurrence. A projected increase in the aging cancer population highlights the need for a better understanding of this phenomenon.METHODSA critical appraisal of the literature evidence in relation to the pattern, pathophysiology, assessment, impact, and management of cognitive dysfunction due to opioid use in cancer pain management is given.RESULTSStudies in cancer patients with less advanced disease reveal subtle evidence of cognitive impairment, largely related to initial dosing or dose increases. In advanced cancer, opioid‐induced cognitive dysfunction usually occurs in the form of delirium, a multifactorial syndrome. The presence of both cognitive impairment and delirium frequently is misdiagnosed or missed. Potential risk factors include neuropathic and incidental pain, opioid tolerance, somatization of psychologic distress, and a history of drug or alcohol abuse. Elevation of opioid metabolites with renal impairment may contribute to cognitive dysfunction. Recognition of opioid‐related cognitive dysfunction is improved by objective screening. Successful management requires either dose reduction or a change of opioid, in addition to addressing other reversible precipitants such as dehydration or volume depletion.CONCLUSIONSOpioid‐related cognitive dysfunction tends to be subtle in the earlier stages of cancer, whereas delirium, a more florid form with behavioral disturbance is likely to be present in the advanced cancer population. In patients with advanced disease, an optimal management approach requires careful clinical assessment, identification of risk factors, objective monitoring of cognition, maintenance of adequate hydration, and either dose reduction or switching to a different opioid. Cancer 2002;94:1836–53. © 2002 American Cancer Society.DOI 10.1002/cncr.10389

show abstract

Hydromorphone-3-glucuronide: Biochemical synthesis and preliminary pharmacological evaluation

Cited by 50 publications

References 33 publications

Delirium and dehydration: some fluid for thought?

Delirium and dehydration: some fluid for thought?

Relationship between plasma concentrations of morphine and its metabolites and pain in cancer patients

The panorama of opioid‐related cognitive dysfunction in patients with cancer

Contact Info

Product

Resources

About