Nitrous oxide Methotrexate

Several drugs, such as the antifolate compound methotrexate or the anaesthetic gas nitrous oxide, may interfere with methionine metabolism and lead to mild increases of Hey [2]. Abnormal renal function has been shown to lead to increased plasma Hey, for example, in end-stage renal disease patients [15]. 

METHOTREXATE ANAESTHETICS-NITROUS OXIDE t antifolate effect of methotrexate t toxicity of methotrexate Nitrous oxide is usually used for relatively brief durations when patients are anaesthetized, and hence this risk during anaesthesia is minimal. However, nitrous oxide may be used for analgesia for longer durations, and this should be avoided... 

Methotrexate-induced stomatitis and other toxic effects may be increased by the use of nitrous oxide. 

A study in which intravenous methotrexate, cyclophosphamide and fluor-ouracil (CMF) were used within 36 hours of mastectomy suggested that stomatitis may be caused by a toxic interaction between methotrexate and nitrous oxide used during anaesthesia. Stomatitis was much more common in those receiving CMF within 6 hours of surgery. " A possible reason is that the effects of methotrexate on tetrahydrofolate metabolism are increased by nitrous oxide, and this has been confirmed in animals It was found that the incidence of stomatitis, severe leucopenia, thrombocytopenia, and of severe systemic and local infections could be reduced by giving calcium folinate (leucovorin) and intravenous hydration. Alternatively, the use of nitrous oxide shortly before methotrexate administration should be avoided. ... 

Goldhirsch Gelber RD, Tattersall MNH, Rudenstam C-M, Cavalli F. Methotrexate/nitrous-oxide toxic interaction in perioperative chemotherapy for early breast cancer. Lancet i 9ZT) ii, 151. 

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