NSAIDS Flashcards
What are the main actions of NSAIDs and what is their basic primary function
Actions - Anti-inflammatory, analgesia and anti-pyretic. Their primary function - inhibition of prostaglandin synthesis by inhibition of cyclo-oxygenase enzyme
What are the two main mechanisms on inhibition of COX
1) an irreversible, time-dependant inhibition.
2) A rapid, reversible competative inhibition of the enzyme
What type of mechanism does aspirin work through and explain in more detail.
Aspirin works via mechanism one (irreversible, time dependant inhibition), It acetylates the binding site where arachadonic acid binds so it can no longer bind
What type of mechanism does ibuprofen work and explain in more detail
Via mechanism two (rapid, reversible competitive inhibition). It reversibly binds to the enzyme and competes with arachidonic acid for the binding site.
What are prostiglandins made from?
Arachidonic acid via the enzyme cyclo-oxygenase. Different enzymes produce different types of COX
What are the two main cyclo-oxygenase enzymes and their features
COX-1 (constitutive and important in the maintenance of GI tract integrity). And COX-2 (expressed when required, involved in inflammatory response and implicated in cancer development)
Describe the role of prostaglandins in inflammation
Inflammation always accompanied by release of prostaglandins, they can cause vasodilation and resultant oedema but have a lesser effect on cellular accumulation or migration.
What is the role of NSAIDs with inflammation
They only effect aspects of inflammation where prostaglandins play big role. So can reduce local signs and symptoms (redness, swelling, heat and pain)
Describe the role of prostaglandins with fevers and how NSAIDs affect this
Fever occurs when hypothalamic set point is raised, bacterial endotoxins cause release of factors from macrophages. Interleukin 1 causes generation of prostaglandins in hypothalamus. Prostaglandins increase set point. NSAIDs prevent formation of prostaglandins so reduce temp.
Describe the role of prostaglandins in pain and the effects of NSAIDs.
Inflamed regions painful due to histamine and bradykinin. Prostaglandins sensitise nociceptive nerves to these compounds. NSAIDs prevent production of prostaglandins so prevent sensitisation to pain-producing compounds (at local level, not in CNS).
describe some of the features of aspirin
Pro-drug (acetylsalicylic acid), metabolised to active compound (salicylic acid) by plasma and tissue esterases. Salicylates found in plasma within 30mins, peak plasma conc in 1-2hrs.
What are some of the unwanted side effects of salicylates?
Stomach (bleeding and ulcers), Systemic (Tinnitus, dizzy, impaired hearing, nausea, vomiting hypersensitivity), Metabolic (acid/base balance affected), Haemostasis (blood coagulation), CNS effects (stimulation, coma and respiratory depression) and renal (insufficiency in susceptible patients).
Name an example of an propionic acid and fenamates.
Propionic acid - ibuprofen and naproxed (well absorbed, not pro drugs, last for 4-6hrs). Fenamates - mefenamic aicd
What are some of the side effects of acetaminophen
Fewer side effects than NSAIDs. However major issue is hepatotoxicity as it usually is inactivated by glucuronate or sulphate conjugation but when these are saturated, toxic metabolites form, can result in hepatic necrosis
Name and describe selective COX-2 inhibitors
Coxibs, eg, celecoxib. Used for both arthritis when traditional NSAIDs produce too severe GI side effects. CV risk needs to be assessed.
