Drugs to Treat Inflammation Flashcards
What is the mechanism of action of glucocorticosteroids?
inhibit arachidonic acid metabolism and release
What is the mechanism of action of NSAIDs?
inhibit cyclooxygenases
What is the mechanism of action of CysLT1 receptor antagonists?
block LTC4 and LTD4 actions
Where is COX-1 located?
constituitively in most cells - makes prostacyclins
Where is COX-2 located?
inducible in inflammatory cells, fibroblasts, smooth muscle and endothelium - makes prostaglandins
What is the relationship between endogenous canabinoids and inflammation?
endogenous canabinois are anti inflammatory
Why aren’t prostaglandins used very much as a drug?
because they are relatively unstable and are difficult to synthesise
What is epoprostenol and what is it used for?
a PGI2 analogue - used in pulmonary hypertension
What is misoprostol and what is it used for?
a PGE1 analogue - used in abortion
What are the effects of NSAIDs?
anti-inflammatory, analgesic, anti-pyretic, anti-aggregatory
Why is aspirin contra indicated in gout?
because it competes with uric acid for excretion in the kidney
What are the gastrointestinal side effects of NSAIDs and why do they occur?
peptic ulcers - occurs because of the lack of protective effects from PGE2 (increase in mucous secretion, decrease in acid secretion, increase in blood flow and promotion of angiogenesis)
Why do NSAIDs cause increased bleeding time?
because they decrease TXA2 synthesis which impairs platelet aggregation
How do NSAIDs compromise renal blood flow?
because of decreased prostacyclin dilation
How do NSAIDs increase blood pressure?
decreased PGE2 natureisis
What patients are at risk of renal failure when given NSAIDs?
elderly patients with hypovolaemia, underlying renal disease and heart failure
Which patients have a hypersensitivity to NSAIDs?
10% of asthmatics who over produce leukotrienes (for unknown reasons) when COX is inhibited causing bronchoconstriction
Why is aspirin special?
because it binds irreversibly to COX so new enzymes need to be synthesised - this is not possible in platelets but is possible in the endothelium so will result in an altered ratio of PGI2/TXA2 - also because of the synthesis of aspirin triggered lipoxins which are implicated in inflammation resolution
What are the side effects of aspirin which are not side effects of other NSAIDs?
Reye’s syndrome, tinnitis, uric acid retention
What is the mechanism of action of paracetamol?
unclear
What is paracetamol used for?
analgesic, anti pyretic - but not anti inflammatory
What are the different side effects for COX-1 and COX-2 selective NSAIDs?
COX-1 selective have gastrointestinal side effects but COX-2 selective have cardiovascular side effects
What percentage of the genome is affected by glucocorticosteroids?
10-20%
What are the 3 mechanisms of action of glucocorticosteroids?
direct transactivation (stimulates gene expression), direct transrepression (inhibits gene expression) and tethered transpression (as a result of interaction with another protein target)
