The absence of early diarrhea with atropine premedication during irinotecan therapy in metastatic colorectal patients

Yumuk, Perran Fulden; Aydın, Sibel Zehra; Dane, Faysal; Gümüş, Mahmut; Ekenel, Meltem; Aliustaoğlu, Mehmet; Karamanoğlu, Ayla Yavuz; Şengöz, Meriç; Turhal, Serdar

doi:10.1007/s00384-004-0613-5

Cited by 24 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Atropine functions by inhibiting the muscarinic actions of acetylcholine released by cholinergic nerve fibres innervating gastrointestinal smooth muscles, as well as inhibiting the actions of cholinergic secretomotor neurons innervating the mucosa. Dosage ranges from 0.25 -1 mg and can be delivered intravenously or subcutaneously as either prophylaxis or treatment for CID, to a maximum cumulative dose of 1.2 mg [60]. It has been found that subcutaneous administration of atropine prior to chemotherapeutic treatment was effective at reducing CID [60] [61].…”

Section: Atropinementioning

confidence: 99%

“…It has been found that subcutaneous administration of atropine prior to chemotherapeutic treatment was effective at reducing CID [60] [61]. However atropine administration is linked to swelling of the lips, tongue and face, irregular or fast heart rate, rash or flushing, eye pain, headache, dizziness, blurred vision, bloating, nausea, heartburn, constipation, weakness, difficulty urinating [60]- [62].…”

Section: Atropinementioning

confidence: 99%

See 1 more Smart Citation

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

McQuade¹,

Bornstein²,

Nurgali³

2014

IJCM

View full text Add to dashboard Cite

Chemotherapy-induced diarrhoea (CID) is a common side-effect experienced by patients being treated with a variety of antineoplastic agents. Approximately 80% of patients undergoing chemotherapeutic treatment for colorectal and other gastrointestinal cancers present with CID; moreover, about 5% of early deaths associated with combination anti-cancer chemotherapy are due to CID. Chronic post-treatment diarrhoea amongst cancer survivors can persist for more than 10 years greatly effecting long-term quality of life. Gastrointestinal toxicities such as diarrhoea and vomiting are amongst the primary contributors to dose reductions and delays throughout anti-cancer treatment, presenting a significant hurdle in clinical management of anti-cancer regimes and often result in sub-optimum treatment. However, little is known about pathophysiological mechanisms underlying CID. This work provides a review of chemotherapy-induced diarrhoea, current management guidelines, and shortcomings of current treatments as well as emerging and already existing anti-diarrhoeal treatments potentially suitable for CID.

show abstract

Section: Atropinementioning

confidence: 99%

Section: Atropinementioning

confidence: 99%

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

McQuade¹,

Bornstein²,

Nurgali³

2014

IJCM

View full text Add to dashboard Cite

show abstract

“…In order to suppress the cholinergic hyperstimulation effect of CPT-11, the anticholinergic drug, atropine, has been routinely used [20,153]. In a study, atropine was required in 34% of patients treated with a relatively high dose of CPT-11, and only one patient experienced grade 3 early diarrhea despite the use of atropine [126].…”

Section: Anticholinergic Agentsmentioning

confidence: 99%

Novel Agents that Potentially Inhibit Irinotecan-Induced Diarrhea

Yang¹,

Chan³

et al. 2005

CMC

View full text Add to dashboard Cite

Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However, severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and severe diarrhea) hinder its clinical use. The latter consists of early and late-onset diarrhea, occurring within 24 hr or > or = 24 hr after CPT-11 administration, respectively. This review highlights novel agents potentially inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea is observed immediately after CPT-11 infusion and probably due to the inhibition of acetylcholinesterase activity, which can be eliminated by administration of atropine. Late-onset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and SN-38 may also stimulate the production of pro-inflammatory cytokines and prostaglandins (PGs), thus inducing the secretion of Na(+) and Cl(-). Early treatment of severe late-onset diarrhea with oral high-dose loperamide has decreased patient morbidity. Extensive studies have been conducted to identify other potential agents to ameliorate diarrhea in preclinical and clinical models. These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P-glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor necrosis factor-alpha (TNF-alpha) inhibitors, or blockers of biliary excretion of SN-38. Further studies are needed to identify the molecular targets associated with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced diarrhea.

show abstract

“…However, dose-limiting toxicities myelosuppression, neutropenia, and gastrointestinal (GI) toxicity, particularly severe late-onset diarrhea, compromise the efficacy and safety of irinotecan-based chemotherapy (Kakolyris et al, 2001; Benson et al, 2004). Prophylaxis with atropine inhibit the activity of cholinesterase to eliminate acute (early-onset) diarrhea (Yumuk et al, 2004). However, high dose of loperamide, recommended to relieve CPT-11-induced severe late-onset diarrhea, is non-specific and shows limited effect (Suzuki et al, 2000; Barbounis et al, 2001; Pro et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by Regulating Bile Acids Metabolism Homeostasis

et al. 2017

View full text Add to dashboard Cite

Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted assays are often less sensitive and/or efficient. In order to further confirm our previous findings, here in this paper, serum and tissues metabolic profiles of 17 BAs were analyzed using liquid chromatography-tandem mass spectrometry based targeted metabolomics. The results indicated that serum and tissues levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that the BAs pool size remained unchanged, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. The present study demonstrated for the first time that the precise interaction between HQD, CPT-11-induced intestinal toxicity and BAs’ homeostasis.

show abstract

The absence of early diarrhea with atropine premedication during irinotecan therapy in metastatic colorectal patients

Cited by 24 publications

References 0 publications

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

Novel Agents that Potentially Inhibit Irinotecan-Induced Diarrhea

HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by Regulating Bile Acids Metabolism Homeostasis

Contact Info

Product

Resources

About