Anti-inflammatories Flashcards
how do glucocorticoids work
these are lipid soluble steroid compunds so they bind to an intracellular receptor which then acts as a transcription factor upregulating desired genes
how do the anti-inflammatory effects of glucocorticoids work
they bind to the receptor which upregulates the transcription of anti-inflammatory enzymes like Lipocortin-1.
lipocortin-1 upregulates interleukin receptor antagonists and down regulates pro-inflammatory cytokines and enzymes like COX and phospholipase
what are some of the cellular effects elicited by corticosteroids
decrease cytokine release by eosinophils and T cells decreases mast cell numbers. reduces endothelial membrane leak, decreases goblet cell mucus secretion,
what are the pertinent effects of corticosteroids in asthma
reduces recruitment/ number of macrophages and inhibit their function, also decreases histamine release from the mast cells and eosinophils - reducing vascular permeability
but do not have effect on bronchodilation
what are some adverse effects of corticosteroids
increase protein catabolism and decrease anabolism. cause redistribution of fats, decrease glucose uptake and utilisation in skeletal muscle
can lead to osteoporosis as vitamin D mediated Ca2+ absorption is inhibited also suppress osteoblast function
can suppress the HPA axis resulting in a lack of endogenous steroid production
can cause immune suppression
how do we get around the adverse effects of corticosteroids when treating asthma
we give it via an inhaled route
PKs of inhaled glucocorticoids
fluticasone is inhaled allows treatment at 1/100th of an oral dose, reducing risk of systemic effects. metabolised by CYP enzymes
what are side effects of inhaled corticosteroids specifically
oropharyngeal candidiasis due to local immune suppression of the mouth
dysphonia - a hoarse throat due to laryngeal deposition of drug particles
how do we reduce ADR of inhaled corticosteroids
rinse the mouth after, gargle antifungal mouth wash. use a spacer to reduce the amount of large droplets that deposit in the mouth
whats the black box warning of inhaled corticosteroids
when switching someone from oral glucocorticoid use to inhaled we have to remember that it takes months for the HPA axis to recover so patient may have some adrenal insufficiency.
so patient may have some immunosuppression or may not cope with stress, so give oral glucocorticoids on a per needed basis.
why do we like the fact that glucocorticoids suppress COX, but also increase lipocortin-1 which inhibits phospholipase as well. and they down regulate phospholipase itself
phospholipase makes membrane phospholipids into arachidonic acid. this AA is then used as a precursor by COX to make prostaglandins which increase vascular permeability and constrict the bronchi
Lipooxygenases can also take AAs and turn them into the leukotriennes. these increase chemotaxis of cells but also increase vascular permeability.
so depressing all of this reduces the inflammatory response of asthma.
