Corticosteroids toxicity

An issue for inhaled corticosteroid treatment is patient compliance. Analysis of prescription renewals shows that corticosteroids are taken regularly by a minority of patients. This may be a function of a general "steroid phobia" fostered by emphasis in the lay press over the hazards of long-term oral corticosteroid therapy and by ignorance over the difference between corticosteroids and anabolic steroids, taken to enhance muscle strength by now-infamous athletes. This fear of corticosteroid toxicity makes it hard to persuade patients whose symptoms have improved after starting the treatment that they should continue it for protection against attacks. 

CORTICOSTEROIDS PROTEASE INHIBITORS-RITONAVIR t plasma levels of betamethasone, dexamethasone, hydrocortisone, prednisolone and both inhaled and intranasal budesonide and fluticasone with ritonavir (with or without lopinavir) Inhibition of CYP3A4-mediated metabolism Monitor closely for signs of corticosteroid toxicity and immunosupression, and i dose as necessaiy. Consider using inhaled bedometasone... 

Corticosteroids (cortisone) Possible increased corticosteroid toxicity Clinical significance not established... 

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

A similar classification scheme is used to gauge the severity of active CD.2 Patients with mild to moderate CD are typically ambulatory and have no evidence of dehydration, systemic toxicity, loss of body weight, or abdominal tenderness, mass, or obstruction. Moderate to severe disease is considered in patients who fail to respond to treatment for mild to moderate disease, or those with fever, weight loss, abdominal pain or tenderness, vomiting, intestinal obstruction, or significant anemia. Severe to fulminant CD is classified as the presence of persistent symptoms or evidence of systemic toxicity despite outpatient corticosteroid treatment, or presence of cachexia, rebound tenderness, intestinal obstruction, or abscess. 

Hydroxyurea is an older agent still used occasionally today for patients with psoriasis however, there have been recent precautions about its use in the elderly and cutaneous vasculitic toxicities in patients with myeloproliferative disorders.29 Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.29 Oral corticosteroids are reserved for severe or life-threatening conditions such as severe psoriatic arthritis or exfoliative psoriasis prolonged oral steroid use should be avoided.10... 

Factors that can predispose patients to developing metabolic bone disease include deficiencies of phosphorus, calcium, and vitamin D vitamin D and/or aluminum toxicity amino acids and hypertonic dextrose infusions chronic metabolic acidosis corticosteroid therapy and lack of mobility.35,39 Calcium deficiency (due to decreased intake or increased urinary excretion) is one of the major causes of metabolic bone disease in patients receiving PN. Provide adequate calcium and phosphate with PN to improve bone mineralization and help to prevent metabolic bone disease. Administration of amino acids and chronic metabolic acidosis also appear to play an important role. Provide adequate amounts of acetate in PN admixtures to maintain acid-base balance. 

Systemic toxicity of inhaled corticosteroids is minimal with low to moderate inhaled doses, but the risk of systemic effects increases with high doses. Local adverse effects include dose-dependent oropharyngeal candidiasis and dys-phonia, which can be reduced by the use of a spacer device. The ability of spacer devices to enhance lung delivery is inconsistent and should not be relied on. 

Systemic corticosteroids (Table 80-4) are indicated in all patients with acute severe asthma not responding completely to initial inhaled /J2-agonist administration (every 20 minutes for three to four doses). Prednisone, 1 to 2 mg/kg/day (up to 40 to 60 mg/day), is administered orally in two divided doses for 3 to 10 days. Because short-term (1 to 2 weeks), high-dose systemic steroids do not produce serious toxicities, the ideal method is to use a short burst and then maintain the patient on appropriate long-term control therapy with inhaled corticosteroids. 

In patients who require chronic systemic corticosteroids for asthma control, the lowest possible dose should be used. Toxicities may be decreased by alternate-day therapy or high-dose inhaled corticosteroids. 

The clinical benefits of systemic corticosteroid therapy in the chronic management of COPD are often not evident, and there is a high risk of toxicity. Consequently, chronic, systemic corticosteroids should be avoided if possible. 

Several types of immunosuppression have also been tried. Azathioprine alone was found to have no effect on PBC [82], but additional benificial effects were found in combination with ursodeoxychohc add and corticosteroids [78]. Cyclosporin showed some success, espe-dally in corticosteroid-resistant autoimmune hepatitis [83], but its use is generally considerably hmited by severe side-effects. Corticosteroids were effective in the management of several types of autoimmune chronic active hepatitis [84,85] and in the management of acute al-cohohc hepatitis [86]. Their use, however, has to be brief hi order to minimize side-effects. In the treatment of PBC, corticosteroids alone were found to be toxic and had only limited efficacy [77]. 

VIII.b.1.3. Extensive disease. Rectal therapies are insufficient, and patients should receive, if outpatients, oral corticosteroids, and if in-patients oral or parenteral corticosteroids with full supportive treatment including parenteral fluids and blood transfusion. The need for intensive in-patient treatment is indicated by the presence of severe diarrhoea, anaemia, fever and tachycardia with radiographic evidence of colonic mucosal oedema on plain X-ray, or of toxic megacolon. 

C. The likelihood of gastric ulceration and GI bleeding is increased by heavy alcohol use, poor health, advanced age, long-term NS AID use, and use of drugs such as corticosteroids and anticoagulants. Ibuprofen is not converted to a cardiotoxic metabolite. Dermal toxicities, such as epidermal necrolysis, are rare complications of ibuprofen therapy, but necrotizing fasciitis is not one of them. Confusion and ataxia are not side effects associated with ibuprofen, nor is eosinophilia. 

Systemic toxicity from topical corticosteroids can occur, particularly from the more potent agents. Cushing s syndrome, although rare, has been reported. 

---