Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 15-year-old girl with homozygous sickle cell anemia (HbSS) and osteosarcoma is described. Delayed clearance of methotrexate (MTX) after the second course of high-dose MTX (HDMTX) led to the development of renal and hepatic toxicities. Rescue was accomplished with high-dose leucovorin, intravenous carboxypeptidase G2, and thymidine. Although the renal and hepatic abnormalities resolved, focal tonic-clonic seizures developed, accompanied by abnormal brain imaging. Four weeks after this episode, all clinical and biochemical abnormalities resolved. Preexistent end-organ damage associated with HbSS may compromise the ability to deliver high-dose chemotherapy with curative intent in patients with malignant disease.
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PMID:Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma. 1020 66

The bacterial enzyme carboxypeptidase G2 (CPDG2) rapidly hydrolyzes methotrexate to inactive metabolites. We administered recombinant CPDG2 (2000 U) intrathecally to seven cancer patients 3 to 9 hours after they had received an accidental overdose of intrathecal methotrexate (median dose = 364 mg; range = 155-600 mg). Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove methotrexate before CPDG2 administration. Immediate symptoms of the methotrexate overdoses included seizures (n = 5), coma (n = 2), and cardiopulmonary compromise (n = 2). Before CPDG2 administration, the median concentrations of methotrexate in CSF were 264 microM (range = 97-510 microM) among patients who had CSF exchange and 8050 microM (range = 2439-16 500 microM) among patients who did not. After intrathecal CPDG2 administration, methotrexate concentrations in CSF declined by more than 98%. All patients recovered completely from the intrathecal methotrexate overdose except for two patients who had memory impairments. Antibodies to CPDG2 were not detected in plasma after treatment with intrathecal CPDG2. Intrathecal CPDG2 is well tolerated, rapidly decreases CSF methotrexate concentrations, and appears to be efficacious for treating accidental intrathecal methotrexate overdoses.
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PMID:Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2. 1584 Aug 87

We report a case of methotrexate toxicity potentially induced by a drug interaction between methotrexate and omeprazole in a 25-year-old man with osteosarcoma. The patient was placed on omeprazole after his first cycle of high-dose methotrexate for stress ulcer prophylaxis, and it was discontinued before the start of the first day of the patient's second round of high-dose methotrexate. The 24-hour methotrexate level was elevated and he continued to have sustained levels for 18 days. Side effects due to elevated serum methotrexate included seizures, mucositis, acute renal failure, and thrombocytopenia. Aggressive hydration, urinary alkalinization, and leucovorin were continued during the period of elevated methotrexate levels, with the patient receiving a course of hemodialysis and a dose of carboxypeptidase G2. The patient's symptoms resolved, and his renal function returned to baseline within 2 months. The patient was able to receive future courses of chemotherapy without methotrexate. Although use of the Naranjo adverse reaction probability scale indicated a probable relationship (score of 6) between the patient's development of methotrexate toxicity and omeprazole use, we believe this was a drug-drug interaction case consistent with previous reports in the literature.
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PMID:Suspected methotrexate toxicity from omeprazole: a case review of carboxypeptidase G2 use in a methotrexate-experienced patient with methotrexate toxicity and a review of the literature. 2255 Jan 62