Corticosteroid therapy adverse effects

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. A athioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable compHcations, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

Corticosteroids, while effective for rapidly inducing remission, are not effective for maintenance therapy and are associated with significant adverse effects with long-term use. Therefore, systemic or topical corticosteroids should not be used for maintaining remission in patients with IBD. Unfortunately up to 50% of patients treated acutely with corticosteroids become dependent on them to prevent symptoms.2... 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Corticosteroids induce a non-specific immunosuppresion. Owing to their overwhelming incidence of adverse events, many practitioners attempt to use low-dose maintenance therapy or, in some cases, complete steroid withdrawal. Corticosteroids are also effective in reversing acute rejection. 

Evaluate the patient for drug interactions, allergies, and adverse effects with chemotherapy and/or corticosteroid therapy. 

Systemic corticosteroid therapy is not recommended in OA, given the lack of proven benefit and the well-known adverse effects with long-term use. 

Low-dose, long-term corticosteroid therapy may be used to control symptoms in patients with difficult-to-control disease. Prednisone doses below 7.5 mg/day (or equivalent) are well tolerated but are not devoid of the long-term corticosteroid adverse effects. The lowest dose that controls... 

Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy. A systematic review and meta-analysis. Arch Intern Med 1999 159 941-55. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

COX-2 specific inhibition good choice for patients with inflammatory conditions who are at high risk of gastrointestinal adverse effects (e.g., older than 60 years history of peptic ulcer disease prolonged, high-dose NSAID therapy concurrent use of corticosteroids or anticoagulants)... 

Theophylline improves long-term control of asthma when taken as the sole maintenance treatment or when added to inhaled corticosteroids. It is inexpensive, and it can be taken orally. Its use, however, also requires occasional measurement of plasma levels it often causes unpleasant minor side effects (especially insomnia) and accidental or intentional overdose can result in severe toxicity or death. For oral therapy with the prompt-release formulation, the typical dose is 3-4 mg/kg of theophylline every 6 hours. Changes in dosage result in a new steady-state concentration of theophylline in 1-2 days, so the dosage may be increased at intervals of 2-3 days until therapeutic plasma concentrations are achieved (10-20 mg/L) or until adverse effects develop. 

Clinical studies of corticosteroids consistently show them to be effective in improving all indices of asthma control—severity of symptoms, tests of airway caliber and bronchial reactivity, frequency of exacerbations, and quality of life. Because of severe adverse effects when given chronically, oral and parenteral corticosteroids are reserved for patients who require urgent treatment, ie, those who have not improved adequately with bronchodilators or who experience worsening symptoms despite maintenance therapy. Regular or "controller" therapy is maintained with aerosol corticosteroids. 

Aerosol treatment is the most effective way to avoid the systemic adverse effects of corticosteroid therapy. The introduction of corticosteroids such as beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone... 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Serious adverse events occur in up to 6% of patients with anti-TNF therapy. The most important adverse effect of these drugs is infection due to suppression of the ThI inflammatory response. This may lead to serious infections such as bacterial sepsis, tuberculosis, invasive fungal organisms, reactivation of hepatitis B, listeriosis, and other opportunistic infections. Reactivation of latent tuberculosis, with dissemination, has occurred. Before administering anti-TNF therapy, all patients must undergo purified protein derivative (PPD) testing prophylactic therapy for tuberculosis is warranted for patients with positive test results. More common but usually less serious infections include upper respiratory infections (sinusitis, bronchitis, and pneumonia) and cellulitis. The risk of serious infections is increased markedly in patients taking concomitant corticosteroids. 

Fears that heavy use of E-agonist inhalers could actually increase morbidity and mortality have not been borne out by careful epidemiologic investigations. Heavy use most often indicates that the patient should be receiving more effective prophylactic therapy with corticosteroids. In general, 62-adrenoceptor agonists are safe and effective bronchodilators when given in doses that avoid systemic adverse effects. 

The treatment of adverse effects of corticosteroids includes symptomatic management and dose tapering on slow withdrawal of drug. Sudden withdrawal of corticosteroids may cause adrenocortical insufficiency and may lead to death. Gradual withdrawal of corticosteroids is advisable, and supplementary corticosteroid therapy should be provided for the patient with a history of corticosteroid withdrawal. 

The common side effects of long-term corticosteroid therapy are summarized in Figure 27.13. [Note Increased appetite is not necessarily an adverse effect, since it is one of the reasons for the use of prednisone in cancer chemotherapy.] The classic Cushing-like syndrome—redistribution of body fat, puffy face, increased body hair growth, acne, insomnia and increased appetite—are observed when excess corticosteroids are present. Increased frequency of... 

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