Neuropsychiatric complications of commonly used palliative care drugs

Jackson, Neil; Doherty, James; Coulter, Simon

doi:10.1136/pgmj.2007.062117

Cited by 45 publications

(21 citation statements)

References 66 publications

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“…Rates are likely to be higher when metoclopramide is prescribed with other dopamine antagonists (e.g., haloperidol, promethazine) that can also induce these side effects in hospice/palliative care practice. 6,7 The overall positive response with acceptable harms of 34% is low given the prevalent use of metoclopramide, although a census point later than 2 days may increase positive responses further. This may in part be due to an inability to measure the benefit of prophylactic use.…”

Section: Discussionmentioning

confidence: 99%

Pharmacovigilance in Hospice/Palliative Care: Rapid Report of Net Clinical Effect of Metoclopramide

Currow

Vella-Brincat²,

Fazekas³

et al. 2012

Journal of Palliative Medicine

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Background: Understanding the performance of prescribed medications in day-to-day practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ''black box'' warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points-baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care.

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Section: Discussionmentioning

confidence: 99%

Pharmacovigilance in Hospice/Palliative Care: Rapid Report of Net Clinical Effect of Metoclopramide

Currow

Vella-Brincat²,

Fazekas³

et al. 2012

Journal of Palliative Medicine

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“…51 In a context of developmental neurotoxicity or embryotoxicity, we could only speculate about a role in the context of the important, albeit poorly understood, role of acetylcholine in early development. 52,53 The connection to Ras pathway and small GTPases might be only indirect considering the role of muscarinic G-protein-coupled acetylcholine receptors in neural development and plasticity.…”

Section: Groebe Et Almentioning

confidence: 99%

Protein Biomarkers for in Vitro Testing of Embryotoxicity

et al. 2010

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There are new challenges for hazard and risk assessment in the chemical industry with regard to REACH legislation in Europe and related activities in the U.S. and Japan, which require the development of novel in vitro models for the molecular characterization of drug- or chemical-related effects replacing conventional animal testing. In the frame of a European FP6 project on reproductive toxicology ( www.reprotect.eu ), we prepared protein samples from mouse embryonic stem cells differentiated into contracting cardiomyocytes according to the validated embryonic stem cell test (EST) protocol, which had been exposed to toxic substances selected by an expert committee from different in vivo categories of embryotoxicity. Lysates were used to carry out the following investigations: (i) identify optimal dose range conditions in the EST that are suitable for (ii) performing a differential quantitative proteomic study of underlying molecular pathways, (iii) define classes of substances with similar proteomic response patterns, (iv) relate these classes to the traditional in vivo categories of embryotoxicity with (v) the final goal to identify novel surrogate protein biomarker candidates for embryo toxicity. We found two distinct classes of toxic substances (Dinoseb, Ochratoxin-A, and Nitrofen vs β-aminoproprionitril, Metoclopramide, Doxylamine succinate, and d-penicillamine) with clear pathway-related differences in their proteomic patterns. Most notably, different responses to cluster 1 and cluster 2 substances were observed for Heat shock protein β-1, Ras-GTPase-activating protein SH3-domain binding protein, Ran binding protein 5, and Calreticulin, Dihydropyrimidinase-like 2 (Ulip2 protein). On the other hand, Heat shock protein 8 and Fscn1 protein were down-regulated by all compounds from both clusters.

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“…Additional drugs known to cause akathisia include metoclopramide, prochlorperazine, promethazine, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors. 3 Prevalence of akathisia in hospice patients is unknown. 1…”

Section: Incidence and Risk Factorsmentioning

confidence: 99%