Corticosteroids anti-inflammatory effects

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

Metabolites (Activity) beclomethasone 17-mono-propionate (active), free beclome-thasone (very weak anti-inflammatory effects) 16 -hydroxy-prednisolone and 6 -hydroxy-budesonide (< 1 % of parent) 67-OH (low corticosteroid potency) ... 

Echinacea (Echinacea purpurea) Uses immune system stimulant prevention/Rx of colds, flu as supportive th apy for colds chronic infxns of the resp tract lower urinary tract Action Stimulates phagocytosis cytokine production T resp cellular activity topically exerts anesthetic, antimicrobial, anti-inflammatory effects Efficacy Not established may X severity duration of URI Available forms Caps w/ powdered herb equivalent to 300-500 mg, PO, tid pressed juice 6-9 mL, PO, once/d tine 2-4 mL, PO, tid (1 5 dilution) tea 2 tsp (4 g) of powdered herb in 1 cup of boiling water Noles/SE Fever, taste p -version, urticaria, angioedema Contra w/ autoimmune Dz, collagen Dz, progressive systemic Dz (TB, MS, collagen-vascular disorders), HIV, leukemia, may interfere w/ immunosuppressive therapy Interactions t Risk of disulfiram-like reaction W/ disulfiram, metronidazole T risk of exacerbation of HIV or AIDS W/ chinacea amprenavir, other protease inhibitors X effects OF azathioprine, basiliximab, corticosteroids, cyclosporine, daclizumab, econazole vag cream, muromonab-CD3, mycophenolate, prednisone, tacrolimus EMS Possible immunosuppression... 

Mechanism of Action Clioquinol is a broad-spectrum antibacterial agent but the mechanism of action is unknown. Hydrocortisone is a corticosteroid that diffuses across cell membranes, forms complexes with specific receptors and further binds to DNA and stimulates transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the anti-inflammatory effects of corticosteroids applied topically to the skin Therapeutic Effect Alters membrane function and produces antibacterial activity Pharmacokinetics Clioquinol may be absorbed through the skin in sufficient amounts. 

The glucocorticoids also have powerful anti-inflammatory effects and when first introduced were considered to be the ultimate answer to the treatment of inflammatory arthritis. Although there are increasing data that low-dose corticosteroids have disease-modifying properties,... 

Other rheumatic diseases in which the corticosteroids potent anti-inflammatory effects may be useful include vasculitis, systemic lupus erythematosus, Wegener s granulomatosis, psoriatic arthritis, giant cell arteritis, sarcoidosis, and gout. 

Corticosteroids Generalized anti-inflammatory effect see Chapter 39 ... 

Melgert et al. studied the delivery of the corticosteroid dexamethasone to fibrotic livers [240], Dexamethasone has more potent and broader anti-inflammatory effects compared with naproxen. It inhibits the release of inflammatory mediators like TNF-a, IFN-y, and IL-6 and acts as an NFkB inhibitor [241, 242], Dexamethasone coupled to albumin (Dexa-HSA) was specifically taken up by sinusoidal cells in fibrotic rat livers, whereas dexamethasone itself was mainly taken up by hepatocytes. In vivo, Dexa-HSA promoted survival in endotoxin-induced liver inflammation in rats [240], In vitro, anti-inflammatory effects of the conjugate were measured in endotoxin-challenged liver slices. Dexa-HSA inhibited the release of nitric oxide and TNF-a in a dose-dependent manner (Melgert et al. unpublished data). To further enhance the delivery to KC at present dexamethasone is coupled to manHSA, and this conjugate is studied with respect to the pharmacokinetic profile and pharmacotherapeutic effects in fibrotic rats. 

The anti-inflammatory effects of corticosteroids reduce CME, vitreous inflammation, and retinal vasculitis. Use of corticosteroids is especially important if the macular area is threatened. Because they are immunosuppressive, they should never be used without concurrent antimicrobial agents. Oral prednisone 40 to 60 mg is given daily for 2 to 6 weeks depending on clinical response. Topical corticosteroids are used for the secondary anterior chamber reaction but have no impact on retinal inflammation, and periocular injections should be used cautiously, if at all, because of their intense anti-inflammatory activity. 

Immunosuppressive drugs can be divided into five basic categories. Corticosteroids such as methylprednisolone and prednisone are a part of virtually all immunosuppressive drug regimens. Corticosteroids block the production of IL-1 and have potent anti-inflammatory effects. Calcineurin inhibitors such as cyclosporine and tacrolimus are also used in a majority of immunosuppressive drug regimens. Calcineurin inhibitors inhibit the production and secretion of IL-2. IL-2 is involved with T-lymphocyte activation and proliferation. Antiproliferative agents such as azathioprine, mycophenolate mofetil, and sirolimus block T-lymphocyte... 

Unlike rheumatoid arthritis, there is no systemic disease associated with osteoarthritis. Treatment of osteoarthritis is with NSAIDs for their analgesic and anti-inflammatory effects. Corticosteroids are not recommended and disease-modifying drugs are not effective in osteoarthritis. 

In connection with the work on the relationship between chemical structure and anti-inflammatory activity, the effect of ursolic acid, betulin, betulinic acid and erythrodiol on a system of chronic dermal edema and cellular proliferation caused by repeated administration of TPA has recently been examined [89], This experimental model of chronic inflammation has considerable selectivity for corticosteroids and leukotriene synthesis inhibitors. Erythrodiol and ursolic acid were significantly effective and also reduced the neutrophil infiltration detected by MPO activity. The lupane derivatives, betulin and betulinic acid, despite their possible steroid-like mechanism of action [47], were not effective in the chronic model. This result could mean that a six-member E ring of the pentacyclic structure is necessary for the activity against a multiple dose of TPA. The data confirm that a hydroxyl group at the C-28 position is important for the activity, as is also true in the case of erythrodiol, and it may explain the anti-inflammatory effect of this compound in each of the methods. 

The most important anti-inflammatory drugs in the treatment of asthma are the corticosteroids and dmgs such as cromolyn and nedocromil that inhibit release of mediators from mast cells and other inflammatory cells. The lipoxygenase inhibitor zileuton probably also exerts an anti-inflammatory effect in asthma. 

The vasoconstrictive property of corticoids may contribute to their anti-inflammatory effects. The mechanisms by which topical corticoids cause vasoconstriction remains unclear but is thought to be related to their inhibition of natural vasodilators, histamine, bradykinins, and prostaglandins [2, 46]. Some have suggested that corticosteroids potentiate norepinephrine [34], while others suggest that corticoids cause the release of norepinephrine [81]. Corticoids are thought to also have a direct effect on vascular endothelial cells. 

Enhancement of the anti-inflammatory effect of cortlcolds by estrogens was reported.Addition of estrogens produced a 3-20 fold reduction of the previously established requirement of corticosteroids for the successful control of skin diseases in women. 

Cronstein B, Kimmel 8, Lenin R, Martiniuk F, Weissmann G. A mechanism for the anti-inflammatory effects of corticosteroids the glucocorticoid receptor regulates leucocyte adhesion to endothelial cells and expression of endothelial-leucocyte adhesion molecule-1 and intercellular adhesion molecule-1. Proc Natl Acad Sci U8A 1992 89 9991-9995. 

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