0630 - NSAIDs Flashcards
What is arachidonic acid?
How does it relate to inflammation?
Product broken down membrane phospholipids due to phospholipase in the presence of ischaemia. Produces COX-1 (constitutive) and COX-2 (inducible and constitutive), which make prostaglandins. These then are acted on by cell-specific isomerases to create prostanoids (eicosanoids) with different effects. So better to hit higher up the chain.
Arachidonic acid can also be broken down by lipoxygenase to produce leukotrienes.
What is the difference between COX-1 and COX 2?
COX-1 Constitutive, involved in many bodily functions
COX-2 Promotes inflammation, produced constitutively and inducible.
How can anti-inflammatory drugs act?
Decrease production of inflammatory compounds
Decrease response to pro-inflammatory products.
How are NSAIDs classified?
Based on selectivity for COX - selective for their receptor (but in reality never specific for it), or non-selective.
What are some nonselective NSAIDS?
Hit COX1 and 2
Aspirin, diclofenac, ibuprofen, indomethacin, ketorolac, naproxen.
What is one selective NSAID?
Selective for COX2
Celecoxib.
What are the three key attributes of NSAIDS?
Analgesic - peripheral nerve sensation mediated by PGE2.
Antipyretic - inhibit PGE2 from resetting hypothalamus
Anti-inflammatory - inhibit PG’s (which are vasodilatory and chemoattractant)
What are the most common side effects of NSAIDS?
Worse in COX-1 than COX-2 selective
GIT - gastritis and ulceration (reduce HCO3- secretion, mucous, and increase acid secretion)
Kidney - Renal dysfunction - Salt and water retention (exacerbate CCF); cause acute kidney injury
Respiratory - bronchospasm in aspirin-sensitive asthma.
COX-2 - Increased risk of cardiovascular events.
What are the key attributes, and MoA of paracetamol? What happens in OD?
Analgesic
Antipyretic
MoA - Cerebral COX-2 or COX-3 inhibition? - central acting
OD - Hepatotoxicity and death. (NAPQI/Glutathione)
