Which of the following statements about glucocorticoid toxicity is incorrect?
Correct Answer: D
Glucocorticoids have widespread effects on a diverse array of tissue types. Ophthalmologic effects include cataracts and increased intraocular pressure. GI effects include gastritis and ulcer formation and occur synergistically with NSAIDs. Glucocorticoids exert broad immunosuppressive effects on both innate and adaptive immunity in a dose-dependent manner. Psychiatric effects range from confusion to psychosis. Serious psychiatric effects occur in approximately 6% of patients, with the most important risk factor being the steroid dose, though notably the dose is not predictive of the time of onset, type, or duration of symptoms. Treatment of steroid psychosis involves expedited dose reduction when possible and the use of antipsychotic medications as needed. Hypothalamic-pituitary axis suppression is unlikely when patients have received less than 5 mg of prednisone daily for any length of time, likely when patients have received more than 20 mg of prednisone daily for 3 or more weeks, and otherwise is uncertain.
Which of the following statements about methotrexate toxicity is correct?
Correct Answer: B
Rapidly dividing cells require high amounts of folates for DNA synthesis. Methotrexate competitively inhibits an enzyme that reduces folate derivatives into molecules suitable for thymidine synthesis, thus preferentially affecting cells in s-phase. Up to 90% of methotrexate is excreted unchanged in the urine. Leucovorin is a reduced folate that bypasses the enzyme inhibited by methotrexate and can rescue cells that have not suffered severe DNA damage from high-dose methotrexate. To be effective, leucovorin must be initiated approximately 24 to 36 hours after methotrexate. In one study, up to 16% of patients receiving high-dose methotrexate develop an erythematous rash. Hepatotoxicity ranging from asymptomatic elevations in transaminases to cirrhosis can occur with highor low-dose methotrexate, and alcohol and other hepatotoxic medications should be avoided. Similarly, pulmonary toxicity that typically takes the form of hypersensitivity pneumonitis may occur with low-dose chronic use of methotrexate or after high doses of the drug, in which case leucovorin does not appear to reduce the risk.
A 52-year-old woman with a history of depression, diabetes, and hypertension, and who has had kidney transplantation 1.5 years ago, presents to the ED with confusion. Laboratory test results (with recent baseline) are notable for:
Which of the following medications is the most likely culprit?
Correct Answer: E
This patient is presenting with evidence of a thrombotic microangiopathy, most likely hemolytic uremic syndrome (HUS). HUS following organ transplantation is commonly due to calcineurin inhibitors (cyclosporine, tacrolimus) and/or mTOR inhibitors (sirolimus, everolimus).
Which of the following side effects is not commonly associated with tacrolimus?
The calcineurin inhibitors cyclosporine and tacrolimus impair the transcription of interleukin-2 and other T cell cytokines. Both drugs exhibit multiple organ toxicities but not adrenal insufficiency. In addition to A-C and E above, these drugs are associated with hypertension, hyperkalemia, hyperlipidemia, infections, nausea/vomiting, and an increased risk of posttransplant lymphoproliferative disorder.
A 63-year-old man with multiple myeloma is admitted to the ICU with neutropenic fever following melphalan treatment in advance of autologous stem cell treatment.
Which of the following toxicities are not commonly associated with alkylating agents?
Alkylating agents include a broad array of chemically diverse drugs that cause cross-linking of DNA in all cells, but have their greatest effect in rapidly dividing cells. Common side effects include pancytopenia, infertility, mucosal injury, alopecia, and increased risk of malignancy. Less common toxicities include hepatic veno-occlusive disease (hepatomegaly, RUQ pain, jaundice, and ascites), pulmonary fibrosis, and hemorrhagic cystitis. Cardiac toxicity occurs but is rare in comparison to the anthracyclines. The dose-limiting toxicity of the alkylating agents is to the bone marrow, with the nadir of neutropenia between 8 and 16 days postadministration followed by recovery at approximately 21 days.
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