Muscle glucocorticoid effects

Glucocorticoids. Figure 2 Cellular effect of glucocorticoids. Glucocorticoids can affect the activation of most resident and infiltrating cells with the airway suppressing either cell number or mediator release or both. In addition, glucocorticoids are able to decrease vascular permeablility (leak) within the airways that causes oedema and increase the expression of (32-receptors in smooth muscle cells. 

There are several underlying mechanisms responsible for posttransplant HTN. Some causes of HTN in transplant recipients may include renal dysfunction, increased sensitivity to endothelin-1 and angiotensin, increased density of glucocorticoid receptors in the vascular smooth muscle, and decreased production of vasodilatory prostaglandins.57 However, one of the most easily recognized causes of posttransplant HTN is the use of corticosteroids and calcineurin inhibitors.58,59 Corticosteroids usually cause sodium and water retention,57 thus increasing blood pressure, whereas calcineurin inhibitors are associated with a number of effects that may result in HTN, including... 

Unlike glucocorticoids, mineralocorticoids have an insignificant effect on carbohydrate volume. They do not exhibit any anti-inflammatory or anti-aUergy properties. They are used for chronic adrenal insufficiency, as well as for raising tonicity and work capacity of muscles. 

Pharmacology These agents are synthetic adrenocortical steroids with basic glucocorticoid actions and effects. Glucocorticoids may decrease number and activity of inflammatory cells, enhance effect of beta-adrenergic drugs on cyclic AMP production, inhibit bronchoconstrictor mechanisms, or produce direct smooth muscle relaxation. Inhaler use provides effective local steroid activity with minimal systemic effect. 

Prompt intensive treatment with corticosteroids may be lifesaving when an excessive inflammatory reaction has resulted in septic shock. A massive infusion of corticosteroids can restore cardiac output and reverse hypotension by sensitizing the response of adrenoceptors in the heart and blood vessels to the stimulating action of catecholamines. This protective role of steroids may be due to a direct effect on vascular smooth muscle. The combination of glucocorticoids and dopamine therapy preserves renal blood flow during shock. 

Anabolic activities of testosterone, such as increases in amino acid incorporation into protein and in RNA polymerase activity, have been demonstrated in skeletal muscle. Apart from the direct anabolic effects in specific tissue, androgens antagonize the protein catabolic action of glucocorticoids. The androgen compounds with the greatest ratio of protein anabolic effects to virilizing effects are the 19-nortestosterone derivatives. Compounds that are used clinically (Table 63.3) include nandrolone phenpropionate (Durabolin), nandrolone decanoate... 

The glucocorticoids have important dose-related effects on carbohydrate, protein, and fat metabolism. The same effects are responsible for some of the serious adverse effects associated with their use in therapeutic doses. Glucocorticoids stimulate and are required for gluconeogenesis and glycogen synthesis in the fasting state. They stimulate phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and glycogen synthase and the release of amino acids in the course of muscle catabolism. 

Glucocorticoids are widely used as drugs to treat arthritis and dermatitis. In pharmacological doses, they are used to suppress various allergic, inflammatory and autoimmune diseases. They are also administered as post-transplant immunosuppressants. Nevertheless, they do not prevent infection and they also inhibit subsequent regenerative processes. Excessive glucocorticoid levels have side effects on many systems, such as the inhibition of bone formation, delayed wound healing, muscle weakness and an increased risk of infection. 

The side effects of glucocorticoids are numerous (see Chapter 29). These drugs exert a general catabolic effect on all types of supportive tissue (i.e., muscle, tendon, bone). Osteoporosis is a particular a problem in the patient with arthritis because many of these... 

The major limitation of the glucocorticoids in any disease is the risk of serious adverse effects. Because of the general catabolic effect of these drugs on supporting tissues, problems with osteoporosis, skin breakdown, and muscle wasting can occur during prolonged... 

To provide optimal immunosuppressant effects, sirolimus is typically combined with glucocorticoids or other immunosuppressants. Sirolimus exerts a number of other beneficial effects, including the ability to inhibit smooth muscle proliferation in blood vessel walls. For this reason, sirolimus is sometimes incorporated into drug-eluting stents that is, a supportive tubular structure (stent) is placed in the lumen of a partially occluded artery, and the drug is released slowly from the stent to help reduce vessel occlusion.64... 

The most significant impact of these drugs on rehabilitation is related to their side effects, especially those of the immunosuppressants. These drugs are typically used in high doses to produce immunosuppressive effects, which are often achieved at the expense of serious and toxic side effects. Many immunosuppressants, especially the glucocorticoids, exert catabolic effects on bone, muscle, and other tissues. Other immunosuppressants, such as cyclosporine and tacrolimus, are neurotoxic and may cause peripheral neuropathies and CNS-related problems in balance and posture. 

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