|Cortisol / Corticosteroids- by drdoc on-line|
Free cortisol diffuses into individual cells
where specific receptor proteins are found in the cytoplasm of corticosteroid-responsive
Corticosteroids inhibit pro-inflammatory cytokine production, including that of interleukin-1 (IL-1), IL-2, the IL-2 receptor, interferon-a (IFN-a) , tumor necrosis factor (TNF) , and perhaps, various colony stimulating factors (CSFs) such as IL-3 . In addition, corticosteroids even in very low concentrations inhibit the synthesis of a variety of pro-inflammatory enzymes, including the macrophage products collagenase, elastase and plasminogen activator .
Lymphocyte proliferation in vitro, and delayed type hypersensitivity in vitro, are inhibited by corticosteroids
Large intravenous (i.v.) doses of corticosteroids given to normal human volunteers increase the numbers of circulating Neutrophils but decrease peripheral lymphocytes, eosinophils, and monocytes . Neutrophilia, for results from a combination of increased release of immature cells from the bone marrow, an increase in circulating half-life, reduced neutrophil egress from blood, and reduced vascular margination of cells.
Prednisolone is rapidly absorbed from the gastrointestinal tract and is reversibly bound to plasma proteins. Prednisolone is rapidly metabolized in the liver, conjugated and excreted in the urine. It disappears from the blood within 1.53 hours, having a half-life of about 1 hour. However, its action at the tissue level lasts considerably longer. Corticosteroids are perhaps the only drugs which reliably, effectively and rapidly suppress synovitis in rheumatoid arthritis (RA). This effect was demonstrated long before their mechanism of action was investigated and cannot be fully explained by the factors described above.
In a recent review of the main clinical trials of corticosteroids in RA it was concluded that in both short and long-term studies corticosteroids are effective anti-inflammatory agents, significantly better than placebo in the relief of pain and stiffness, and superior to nonsteroidal anti-inflammatory drugs (NSAIDs). However, benefits are not sustained unless increasingly high doses are employed, so that side effects and adrenal suppression preclude their long-term use in RA except in specific circumstances. Several studies appear to suggest that corticosteroids may possess disease-modifying properties. In a follow-up study of the original patient cohort of the early UK studies, the evidence suggested that over the first 4 years of treatment corticosteroids inhibited the development of erosions. There are also studies which support the contention that corticosteroids may be useful in improving or maintaining function.
There is no doubt that low doses of corticosteroids in dosages up to 10mg/day are effective anti-inflammatory agents. It is not clear, however, whether they do possess disease-modifying activity . Moreover, the use of oral low-dose corticosteroids as supplementary anti-inflammatory agents may be advocated because their side-effects profile is more acceptable than those of other immunosuppressive agents.
From drdoc - Edited with help from SYSTEMIC CORTICOSTEROIDS IN RHEUMATOLOGY John R Kirwan Rheumatology by Klippel and Dieppe 8.11
Low dose and trim thereafter when the second
line agents start kicking in.
My technique is different for different individuals. I don't believe that one should lower the dose in an uncompromising regimented fashion in the rheumatic diseases. Each person and their disease is different...
I avoid getting into the situation of mega-doses
for my patients unless they have systemic organ disease involvement i.e. cardiac/pulmonary/vasculitis etc...
Once I am reducing down from 10mg,
by 2.5 mg at a time - but slowly..
This may mean 1-3 months or more between reductions
if so required.
Once I am at 2.5mg.. I start to go..
If at any stage the patient flares ---I go back to the previous level and retry from that level in a structured but individualized manner
The important thing is to ensure that whilst this is all happening, the disease itself is being controlled using DMARDS at a deeper level.
These should generally be avoided if possible as there is a danger of withdrawal causing a flare of pustular psoriasis. However - I have found intra-articular steroids and soft tissue injections to be safe and effective.
in Systemic disease
A second method includes "pulse" therapy - where a dose of methyl Prednisolone is given - at a dose of 250 mg - 1 gram in a saline infusion over 30-60 minutes. The frequency of these pulses depends on the disease entity i.e. diagnosis and the severity of disease. A common method is to pulse daily for three days, and then possibly to use oral steroids. Alternatively, periodic pulse therapy can be given - and trials of monthly to three monthly pulses have been used for example in the nephritis of systemic lupus erythematosus.
Back to drugs
Back to drdoc on-line homepage
Back to arthritis index page
Go to top of page
Dr David Gotlieb