Non-Steroidal Anti-Inflammatory Drugs Flashcards
What are the three main properties of NSAIDs?
Anti-pyretic, anti-inflammatroy, analgesic
What are prostanoids?
Lipid mediators derived from arachidinoc acid. Mainly prostaglandins i2, E2, D2 and F2A, and thrmboxane. Their synthesis is inhibited by NSAIDs.
What do the coxib family selectively inhibit and give an example
COX2 , celecoxib.
Describe the recpetors of PGE2
There are 4. EP1 and EP3 cause increased intracelular calcium and EP3,2 and 4 cause increased cAMP.
Name5 unwanted effects of PGE2.
Increased pain perception, thermoregulationby hypothalamic effects (fever), acute inflammatory responses, tumoruigenesis, inhibition of apoptosis.
Which receptors and enzyme are involved with a low pain threshold?
EP1 (Ca) and EP4 (cAMP) as well as possibly endocannioboids. COX2 (known becauase COX2 inhibitors reduce duration of pain)
Give an example of PGE2 in acute inflammation.
EP3 receptors on mast cells cause histamine release after PGE2 stimulation form keratinocytes.
Give 4 desirable effects of PGE2.
Gastroprotection, bronchodilation, vasoregulation and renal salt and water homeostasis.
How does PGE2 give gastroprotection?
COX1 mediated, via EP1 and EP3 (so Ca). Increases mucus and bicabonate sceretuon and downregulates HCl secretion.
Desrcibe how PGE2 mediates renal function
It regulates salt and water hoemstais- COX1 mediates the loop of Henle and COX2 mediates the collecting duct. Through vasoregulation, they also affect renal blood flow- blocking PGE2 production can constrcution of the afferent areriole and hence a reduced EGFR.
Give 2 theories why NSAIDs can make people asthmatic
1) Blcoking COX enzymes favours production of leukotreines which are bronchoconstrictors. 2) PGE2 ha s a proetctive function in itelf.
When compared to COX1 inhibitors, why are COX2 inhibtiros good and bad?
Good because they confer more gastroprotection and pain reduction than COX1 inhibitors. Bad becuase stronger assocaition with CVD disease.
How might blocking COX2 cause CVD? (5)
Decreased PGE2 means 1) dysregulation of renal salt and water and 2) decreased protection to cardiac mycoytes against oxidate onjury. Decreased PGI2 means 3) less NO and more platelet activation, 4) also decreased cardiac myocyte protection and 5) decreased RBF and GFR.
How can you limit GI side effects with COX1 inhibitors?
Topical application, treat H pylori, adminsiter with a PPI, reduce risk fators like steroid use and alchohol consumptio.
Why do we give low dose aspirin?
Becuase it irreversibly binds COX1. TXA2 is madejust by COX1 in the platelets so we won’t to knock this out, But COX1 with COX2 makes prostacyclin in the endothelial cells - low dose allow endothelial resyntehsis of COX2 which reduces platelet aggrgation.
