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| which two glucocorticoids bind to the GR receptor with the greast affinity | Budesonide and Fluticasone
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| Binding to the receptor can either result in the | activation or suppression of genes involved in the inflammatory process.(inhibition of transcription of genes coding for cytokines/activate genes that produce anti-inflammatory mediators)
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| anti-inflammatory mediators | lipocortin-1, endonucleases and endopeptidases
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| Lipocortin is a phospholipase A2 inhibitor and is significant in asthma how | This in turn prevents the conversion of membrane phospholipids to arachidonic acid and the synthesis of the leukotrienes LTC4 and LTD4 and LTB4. This in turns makes it a anti inflammatory mediator
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| by preventing the formation of LTC4 and LTD4 what does this do | limits the amount of bronchonstriction that can happen since these cause contrition in asthma
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| LTB4 is a chemotaxin that | recruits inflammatory cells.
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| The outcome of activating lipocortin synthesis, therefore, is to inhibit production of | LTC4 , LTD4 and LTB4, and consequently, bronchospams prevented and recruitment of inflammatory cells, respectively.
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| what is the most effective drug class for the treatment of chronic asthma | glucocorticoids
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| Used long term, corticosteroids reduce | airway responsiveness to several bronchoconstrictor mediators and block both the early and late reactions to allergen
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| Early anti-inflammatory effects of corticosteroids include | Reduce inflammatory cell activation, reduce mucosal edema, decrease local generation of inflammatory prostaglandins and leukotrienes
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| Long-term anti-inflammatory effects of corticosteroids include | t-cell, mast cell, eosinophil reduction
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| glucocorticosteroids eventually reduces the early-phase response to allergens and prevents exercise-induced asthma by which mechanisms | believed to be through the reduction the synthesis of IL-3, the cytokine that regulates mast cell production.
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| Certain corticosteroids - beclomethasone - | have low absorption across mucosal surfaces, but undergoes slow inactivation once it reaches the systemic circulation.
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| Fluticasone is | very poorly absorbed from the gut and maybe preferred if high doses of inhaled drug are needed, or for the treatment of children.
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| Ciclesonide | is a newly approved ICS for asthma (Alvesco).
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| ciclesonide (alvesco) | delivered as a pro-drug, converted in the lung to (desisobutyryl ciclesonide ) by carboxy- and cholinesterases. also remains in the lung for a prolonged peirod of time because the active metabolite is conjugated to lipids forming a “reservoir”
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| side effects of ICS are | dysphonia horseness and oral candidiasis
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| what are some systemic effects of corticoids | osteoporosis and delayed growth the new drug ciclesonide is not shown to cause either of the side effects local or systemic
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| glucocorticoids affects on bone | Increase osteoclast, increase collagenase gene, inhibit osteoblasts, effect collagen synthesis, decrease anabolic IGF-1, increase Ca2+ clearance by kidneys, increase parathyroid hormone, increase bone loss by decrease sex hormones
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| who should we use glucocorticoids with caution in | rhemotoid athristis, cataract risk, those with glucoma or a risk, those with pancretitis,
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| prednisolone is associated with | increased edema
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| more selective to mineralcorticoid can lead to | muscle weakness and muscle wasteing
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