Hemorrhagic cystitis, cyclophosphamide causing

Few side effects can be alleviated by the use of antidotes. An example is the prevention of hemorrhagic cystitis caused by cyclophosphamide by the concomitant infusion of mesna. 

The answer is c. (Hardman, pp 1238-1239.) Remission maintenance can be carried out by combination therapy, which includes cyclophosphamide. Cyclophosphamide causes hemorrhagic cystitis. Doxorubicin and carmustine are useful in the treatment of acute lymphatic leukemia, but neither is known to cause hemorrhagic cystitis. 

Cyclophosphamide (Cytoxan and Endoxan) is used in the treatment of Hodgkin s disease, lymphosarcoma, and other lymphomas. It is employed as a secondary drug in patients with acute leukemia and in combination with doxorubicin in women with breast cancer. A drug combination effective in the treatment of breast cancer is cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP). Cyclophosphamide is also an immunosuppressive agent. The toxicity of cyclophosphamide causes alopecia, bone marrow depression, nausea and vomiting, and hemorrhagic cystitis. 

Cyclophosphamide causes significant dose-related infertility in both men and women as well as bone marrow suppression, alopecia, hemorrhagic cystitis, and, rarely, bladder carcinoma (see Chapter 55 Cancer Chemotherapy). 

In bone marrow transplant recipients, prior administration of busulfan, which itself causes hemorrhagic cystitis, can increase the risk of cyclophosphamide-induced damage (38). 

Hemorrhagic cystitis and bladder cancer are well-known complications of cyclophosphamide. The damage to the urinary bladder epithelium is caused by acrolein, a metabolite of cyclophosphamide that is excreted in the urine. In bone marrow transplant recipients, prior administration of busulfan, which itself causes hemorrhagic cystitis, can increase this risk (23). Mesna (2-mercaptoethane sodium sulfonate) is used to prevent this adverse effect. It is excreted by the kidney, and it binds and detoxifies acrolein in the urine mesna also prevents the breakdown of acrolein precursors. Intravesical prostaglandin E2 has been suggested as an alternative treatment (23). 

Like alprostadil and other prostaglandins, dinoprostone has also been used in the management of hemorrhagic cystitis, especially that caused by cyclophosphamide (309), and in cardiovascular disease, including Raynaud s... 

Drug therapy may also cause renal insufficiency due to lower urinary tract obstruction. Ureteral obstruction can be caused by calculi or retroperitoneal fibrosis. Bladder dysfunction with urinary outflow obstruction can result, particularly in males with prostatic hypertrophy, from anticholinergic drugs including tricyclic antidepressants and disopyramide. Bladder outlet and ureteral obstruction may result from bladder fibrosis following hemorrhagic cystitis with cyclophosphamide or ifosfamide therapy. Concurrent treatment with mesna can prevent cystitis and this complication. 

The immunosuppressive effect of cytotoxic agents, with or without the concurrent use of steroids, can result in serious infections, which are the primary cause of death in patients with minimal-change nephropathy. Other toxicities associated with cyclophosphamide include gonadal fibrosis, which results in sterility, hemorrhagic cystitis, alopecia, and a potential to develop malignancy in those on long-term treatment. Patients on chronic steroid therapy often develop growth retardation, osteoporosis, obesity, and cataracts. ... 

Toxicity Gastrointestinal distress, myelosuppression, and alopecia are expected adverse effects. Hemorrhagic cystitis due to the formation of acrolein may be decreased by vigorous hydration and by use of mercaptoethanesulfonate (mesna). Cyclophosphamide may also cause cardiac dysfunction, pulmonary toxicity, and a syndrome of inappropriate ADH secretion. 

Toxicity Large doses of the drug (usually needed for immunosuppression) cause pancytopenia, gastrointestinal distress, hemorrhagic cystitis, and alopecia. Cyclophosphamide (and other alkylating agents) may cause sterility. 

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