Corticosteroids

In Osteoarthritis:

• Systemic corticosteroid therapy is not recommended in OA, given the lack of proven benefit and the well-known adverse effects with long-term use.
• Intraarticular corticosteroid injections can provide relief, particularly when a joint effusion is present. Average doses for injection of large joints in adults are methylprednisolone acetate 20 to 40 mg or triamcinolone hexacetonide 10 to 20 mg. After aseptic aspiration of the effusion and corticosteroid injection, initial pain relief may occur within 24 to 72 hours, with peak relief occurring in about 1 week and lasting for 4 to 8 weeks. The patient should minimize joint activity and stress on the joint for several days after the injection. Therapy is generally limited to three or four injections per year because of the potential systemic effects of the drugs and because the need for more frequent injections indicates poor response to therapy.

Corticosteroids, synthetic steroid drugs made from the natural hormone hydrocortisone, and particularly prednisone, are frequently used for combination therapy for treating severe and chronic lymphocyte leukemia, Hodgkin’s and non-Hodgkin’s lymphomas, multiple myeloma, and breast cancer. Corticosteroids exhibit an antitumor effect by binding with corticosteroid receptors that exist in many cancerous lymphoma cells, which leads to inhibition of both glucose transport and phosphorylation, which reduces the amount of energy necessary for mitosis and protein synthesis, which, accordingly, leads to cell lysis.

Serious adverse effects are produced by long-term, high-dose exposure to the corticosteroids; therefore, these drugs are not agents of choice for the treatment of rheumatic disease. In general, the use of low-dose corticosteroids avoids significant side effects (e.g. fluid retention, osteoporosis, GI bleeding, immunosuppression) but does not completely control the disease. However, for patients whose disease is refractory to other agents or who cannot tolerate the side effects of other DMARDs, a corticosteroid such as prednisone may be used to control symptoms. Low-dose corticosteroids may also be used as an alternative to more toxic DMARDs in pregnant, elderly, or debilitated individuals. Intraarticular injection of corticosteroids can control acute inflammation of a specific joint without causing systemic side effects. High-dose steroids can control severe systemic manifestations of autoimmune disease, such as iritis, pericarditis, nephritis, or vasculitis. Following discontinuation of corticosteroid treatment, rebound joint deterioration is common.

A major breakthrough in asthma therapy was the introduction in the 1970s of aerosol corticosteroids. These agents maintain much of the impressive therapeutic efficacy of parenteral and oral corticosteroids, but by virtue of their local administration and markedly reduced systemic absorption, they are associated with a greatly reduced incidence and severity of side effects. The success of inhaled steroids has led to a substantial reduction in the use of systemic corticosteroids. Inhaled corticosteroids, along with β2-adrenoceptor agonists, are front-line therapy of chronic asthma.

All corticosteroids have the same general mechanism of action; they traverse cell membranes and bind to a specific cytoplasmic receptor. The steroid-receptor complex translocates to the cell nucleus, where it attaches to nuclear binding sites and initiates synthesis of messenger ribonucleic acid (mRNA). The novel proteins that are formed may exert a variety of effects on cellular functions. The precise mechanisms whereby the corticosteroids exert their therapeutic benefit in asthma remain unclear, although the benefit is likely to be due to several actions rather than one specific action and is related to their ability to inhibit inflammatory processes.At the molecular level, corticosteroids regulate the transcription of a number of genes, including those for several cytokines.
The corticosteroids have an array of actions in several systems that may be relevant to their effectiveness in asthma. These include inhibition of cytokine and mediator release, attenuation of mucus secretion, upregulation of β-adrenoceptor numbers, inhibition of IgE synthesis, attenuation of eicosanoid generation, decreased microvascular permeability, and suppression of inflammatory cell influx and inflammatory processes. The effects of the steroids take several hours to days to develop, so they cannot be used for quick relief of acute episodes of bronchospasm.

The use of corticosteroids is often suggested for elderly patients with chronic tophaceous gout, since gout in the older individual often displays symptoms similar to those of rheumatoid arthritis. Patients can be given short-term administration of corticosteroids, especially for acute flare-ups.The concomitant use of alcohol, nonsteroidal antiinflammatory drugs, and most diuretics should be avoided.

The corticosteroids are effective in most children and adults with asthma. They are beneficial for the treatment of both acute and chronic aspects of the disease. Inhaled corticosteroids, including triamcinolone acetonide (Azmacort), beclomethasone dipropionate (Beclovent, Vanceril), flunisolide (AeroBid), and fluticasone (Flovent), are indicated for maintenance treatment of asthma as prophylactic therapy. Inhaled corticosteroids are not effective for relief of acute episodes of severe bronchospasm. Systemic corticosteroids, including prednisone and prednisolone, are used for the short-term treatment of asthma exacerbations that do not respond to β2-adrenoceptor agonists and aerosol corticosteroids. Systemic corticosteroids, along with other treatments, are also used to control status asthmaticus. Because of the side effects produced by systemically administered corticosteroids, they should not be used for maintenance therapy unless all other treatment options have been exhausted.
A fixed combination of inhaled fluticasone and salmeterol (Advair) is available for maintenance antiinflammatory and bronchodilator treatment of asthma.

The side effects of corticosteroids range from minor to severe and life threatening. The nature and severity of side effects depend on the route, dose, and frequency of administration, as well as the specific agent used. Side effects are much more prevalent with systemic administration than with inhalant administration.The potential consequences of systemic administration of the corticosteroids include adrenal suppression, cushingoid changes, growth retardation, cataracts, osteoporosis, CNS effects and behavioral disturbances, and increased susceptibility to infection. The severity of all of these side effects can be reduced markedly by alternate-day therapy.
Inhaled corticosteroids are generally well tolerated. In contrast to systemically administered corticosteroids, inhaled agents are either poorly absorbed or rapidly metabolized and inactivated and thus have greatly diminished systemic effects relative to oral agents. The most frequent side effects are local; they include oral candidiasis, dysphonia, sore throat and throat irritation, and coughing. Special delivery systems (e.g., devices with spacers) can minimize these side effects. Some studies have associated slowing of growth in children with the use of high-dose inhaled corticosteroids, although the results are controversial. Regardless, the purported effect is small and is likely outweighed by the benefit of control of the symptoms of asthma.