Glucocorticoids toxicity risk

A possible risk of glucocorticoid treatment of ulcerative colitis is the development of toxic megacolon or colonic... 

A possible risk of glucocorticoid treatment of ulcerative colitis is the development of toxic megacolon or colonic perforation. A change from ulcerative colitis to Crohn s disease may have been induced by prolonged treatment with glucocorticoids (SEDA-19, 376) (130). This case provides further evidence for the view that ulcerative colitis and Crohn s disease may represent a continuous spectrum of inflammatory bowel disease and raises the possibility that reduced polymorphonuclear leukocyte function caused by glucocorticoids may have provoked the development of granulomata. 

Although there is no direct evidence of potentiation of hematological toxicity, the concomitant use of drugs that are known to carry a risk of blood dyscrasias is unwise. Simultaneous use of glucocorticoids in small doses is not thought to detract from the beneficial effects of gold and can delay the onset of adverse reactions (39)... 

In a retrospective review of 70 patients with hepatitis C enrolled in four clinical trials, there were four cases of significant pulmonary toxicity (two of bronchiolitis obliterans and two of interstitial pneumonitis) (45). Three recovered completely, but one still required glucocorticoids for exertional dyspnea that persisted 17 months after interferon alfa withdrawal. The authors suggested that there was an increased risk with high-dose interferon, because three of these patients received high doses (5 MU/day) or pegylated interferon alfa. In contrast, they were unaware of any significant pulmonary... 

In an attempt to reduce the toxicity of AG, some workers [102, 103] have used low doses without corticosteroid replacement. Results have been contradictory one group [102] has found that suppression of oestrogen is dose-dependent, while others [103] have found that a dose of 250 mg/day of AG alone was as effective as the standard dose of 1,000 mg plus 40 mg of hydrocortisone. Low-dose regimens have been reported to produce response rates similar to the conventional regimen [103], but other investigators [104] have concluded that the two regimens are not equally effective, and, moreover, that failure to replace glucocorticoid may present the risk of adrenal insufficiency. 

Nephrotoxicity is the principal dose-limiting side effect of intravenous cidofovir. Proximal tubular dysfunction includes proteinuria, azotemia, glycosuria, and metabolic acidosis. Concomitant oral probenecid and saline prehydration reduce the risk of renal toxicity. On maintenance doses of 5 mg/kg every 2 weeks, up to 5Wo of patients develop proteinuria, 10-15% show an elevated serum creatinine, and 15-20% develop neutropenia. Anterior uveitis that is responsive to topical glucocorticoids and cycloplegia occur commonly and ocular hypotony occurs infrequently with intravenous cidofovir. Administration with food and pretreatment with antiemetics, antihistamines, and/or acetaminophen may improve tolerance. 

Toxicity The principal adverse reactions to cyclosporine therapy are renal dysfunction, tremor, hirsutism, hypertension, hyperhpidemia, and gum hyperplasia. Hyperuricemia may lead to worsening of gout, increased P-glycoprotein activity, and hypercholesterolemia. Nephrotoxicity occurs in the majority of patients treated and is the major indication for cessation or modification of therapy. Hypertension occurs in -50% of renal transplant and almost all cardiac transplant patients. Combined use of calcineurin inhibitors and glucocorticoids is particularly diabetogenic, although this apparently is more problematic in patients treated with tacrohmus see below). Especially at risk are obese patients, African American or Hispanic recipients, or those with family history of type 2 diabetes or obesity. Cyclosporine, as opposed to tacrolimus, is more hkely to produce elevations in low-density lipoprotein (LDL) cholesterol. 

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