Mechanisms and Treatment of Radiation-Induced Nausea and Vomiting

Young, Robert W.

doi:10.1007/978-3-642-70479-6_8

Cited by 18 publications

(5 citation statements)

References 30 publications

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“…Our results with ferrets suggest that a high dose of domperidone may slightly reduce the severity of radiation-evoked emesis, but this apparent reduction was not statistically significant. Different intensities of X-irradiation may account for the different results between experimentors (Young, 1986). However, if dopamine receptors do have a role in the mechanism by which radiation can evoke emesis, the prevention of radiation-evoked emesis by BRL 24924 suggests that their involvement may be dominated by a more essential role of 5-HT3 receptors.…”

Section: Discussionmentioning

confidence: 99%

Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis

Miner

Sanger²,

Turner³

1987

Br J Cancer

113

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Summary The involvement of 5-hydroxytryptamine (5-HT) 5-HT3 receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT3 receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT3 receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT3 receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.There have recently been two important advances relating to the improvement of anti-emetic treatment given to patients undergoing anti-cancer therapies. Firstly, it was found that, unlike conventional doses of metoclopramide (Maxolon; Beecham Pharmaceuticals) which antagonise dopamine receptors and stimulate gastric motility, high doses of the drug greatly reduced cis-platin-evoked emesis (Gralla et al., 1981). In contrast, even high doses of the dopamine antagonists, domperidone (Motilium; Janssen Pharmaceuticals) or alizapride, have little or no ability to prevent cis-platininduced emesis (Tonato et al., 1985;Saller & Hellenbrecht, 1985). Mechanisms other than dopamine receptor antagonism have therefore been implicated in this antiemetic action of metoclopramide (McRitchie et al., 1984).Secondly, metoclopramide is an antagonist of 5-hydroxytryptamine (5-HT) acting on 5-HT3 receptors (previously known as 5-HT M-receptors; see Bradley et al., 1986 for definition of this receptor) located in the peripheral nervous system (Fozard, 1984a); the effective concentrations of metoclopramide are higher than those required to antagonise dopamine receptors or to stimulate gut motility (Sanger, 1984). We subsequently suggested that such high doses of metoclopramide may prevent cis-platin-induced emesis by means of antagonising 5-HT3 receptors .The involvement of 5-HT3 receptors in the mechanisms of emesis have now been further investigated using chemo-and radio-emetic stimuli in the ferret. The ferret has previously been shown to be suitable for studying emesis evoked by cisplatin (Florczyk et al., 1982;), a combination of doxorubicin and cyclophosphamide (Schurig et al., 1984) or by whole-body irradiation (Andrews et al., 1986;Gylys & Gidda, 1986

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Section: Discussionmentioning

confidence: 99%

Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis

Miner

Sanger²,

Turner³

1987

Br J Cancer

113

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“…The prodromal syndrome is a group of symptoms and signs of acute gastrointestinal effects that may begin to occur within a few hours of brief whole-body irradiation with gamma rays at doses of 0.5 Gy and greater (Scott and Hahn 1985). The symptoms include anorexia, nausea, vomiting, diarrhoea, intestinal pain and salivation (Young 1986). As discussed by King (1995), the primary radiation target for evoking these responses is the gastrointestinal tract, possibly involving the release of 5-hydroxytryptamine from mucosal cells, activating the 'vomiting centre' in the brainstem either via afferent neural pathways or transfer to chemoreceptors via the bloodstream.…”

Section: Health Effectsmentioning

confidence: 99%

The polonium-210 poisoning of Mr Alexander Litvinenko

et al. 2017

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Mr Litvinenko died on 23 November 2006 after having been poisoned with polonium-210 on 1 November. Measurements of the polonium-210 content of post-mortem tissue samples and samples of urine and blood showed the presence of large amounts of Po. Autoradiography of hair samples showed two regions ofPo activity, providing evidence of an earlier poisoning attempt during October 2006, resulting in absorption to blood of about one-hundredth of that estimated for 1 November. Intake by ingestion on 1 November was estimated to be around 4 GBq, assuming 10% absorption to blood, and the resulting organ doses reached estimated values that were generally in a range from about 20 Gy to over 100 Gy. Comparison with estimates of protracted alpha particle doses required to cause irreversible organ damage supported the conclusion that death was the inevitable consequence of multiple organ failure, with destruction of the haemopoietic bone marrow, as well as damage to kidneys and liver, being important contributors. If the earlier poisoning during October 2006 had not been followed by a second major intake on 1 November, it is possible that the earlier intake of around 40 MBq, with absorption of 4 MBq to blood, might have caused irreversible kidney damage over a prolonged period of months or years, with doses of approaching 3 Gy.

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“…Les nausées et les vomissements induits par ce type de rayonnement sont importants et leur prophylaxie est particulièrement difficile [33,40]. Nos travaux expérimentaux ont été conduits chez le macaque cynomolgus.…”

Section: Effet Antiémétique De L'ondansétron Ou Du Granisétronunclassified