Many autoimmune diseases such as the ones you learned in AP 1 (Multiple sclerosi

Question

Many autoimmune diseases such as the ones you learned in AP 1 (Multiple sclerosis, rheumatoid arthritis) and the current ones in Study Guide Endo 4 (Hashimoto Thyroiditis and Graves Disease) involve treatments with large doses of corticosteroids such as cortisone.

1. Why is cortisone treatment and related drugs desirable for such diseases?

2. Usully treatments involve injections of large doses but done via the intramuscular route or IM ( i.e. vastus lateralis) as opposed to the intravenous route or IV. Explain why IM may be better than IV injections.

Trying to figure this one out, any help would be awesome. Thanks

Explanation / Answer

1)

Corticosteroids can be used to induce a remission or reduce the morbidity in autoimmune diseases. All corticosteroid drugs are chemical modifications of natural glucocorticosteroids. They only differ from cortisone and hydrocortisone by the addition of a double bond in the 1,2 position . To become active, prednisone must be converted to prednisolone by changing the 11-keto group to 11-hydroxyl. The glucocorticoid activity of prednisone and prednisolone is 3-4 fold greater than hydrocortisone . The addition of a 6a-methyl group to prednisolone creates methylprednisolone, which has 5-6 times the activity of hydrocortisone.

Corticosteroids induce a transient lymphocytopenia by altering lymphocyte recirculation. They also induce lymphocyte death. The most important immunosuppressive effect of corticosteroids is on T cell activation, by inhibition of cytokine and effect or molecule production. In this action, they are similar to cyclosporin, although the intracellular pathways by which the two classes of drug achieve this effect are quite separate.

In diseases like rheumatoid arthritis, the aim should be to use the minimum dose required to gain symptomatic relief. A typical starting dose is 5-7.5 mg/day of prednis(ol)one or up to 20 mg to gain initial control of symptoms. Corticosteroids are also used for intra-articular injections of painful joints. In diseases which respond to corticosteroids , oral therapy, usually beginning with 1-2 mg/kg prednis(ol)one, is started with a plan to taper over time to a maintenance dose or to cease the therapy. Clear therapeutic goals can be set such as reduction in proteinuria, reduction in weakness and muscle enzymes, improved blood counts or lung function studies.

2)

Dosage and route of administration depend on the disorder being treated. Parenteral administration of high doses may be warranted in emergencies, such as septic shock and severe acute asthma. Intravenous ("pulse") bolus doses of 1 to 2 g of methylprednisolone have been used to treat transplant rejection and some autoimmune diseases such as severe lupus nephritis and crescentic glomerulonephritis. Another possible mechanism is a direct effect upon cell membranes. In extremely high doses, glucocorticoids dissolve in cell membranes, thereby altering their physicochemical properties and the activities of membrane-associated proteins.

Injected glucocorticoids vary considerably in the rate of their absorption. Hydrocortisone salts are absorbed from an intramuscular injection site within minutes, and less soluble esters are absorbed within one hour. Cortisone acetate is more slowly absorbed, and triamcinolone salts and esters are absorbed even more slowly. Absorption from intraarticular sites can be highly variable. As an example, a single large intrabursal injection of dexamethasone can cause persistent Cushing's syndrome. All topical and inhaled glucocorticoids are absorbed to some extent and, therefore, have the potential for causing hypothalamic-pituitary-adrenal axis suppression and Cushing's syndrome

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