NSAIDs Flashcards
Give examples of NSAIDs
Ibuprofen
Naproxen
Diclofenac
What are the 3 primary effects of NSAIDs?
Analgesia
Anti-inflam
Antipyretic
What is the role of inflammation?
Protective = reduce risk of further damage by MO
What are autacoids?
Local molecular mediators/signalling agents with a short half life
Induce expression of COX 2
E.g. Bradykinin, histamines, cytokines, leukotrienes
What is the role of cyclo-oxylase (COX) enzymes?
Aid the synthesis of prostaglandins
COX 1/2 produce PGs D, E, F, I
E = most important in mediating inflam response
COX 1 = constitutively expressed (constant) in wide range of tissues
COX 2 = induced by injurious stimuli like inflam mediator bradykinin
What is the main therapeutic effect of NSAIDs?
COX 2 competitive inhibition = prostaglandin synthesis inhibition = inflam inhibition
Most ADRs caused by NSAIDs are due to what?
COX 1 inhibition
How do prostaglandins work?
Bind GPCRs
Binding enhances actin of other autacoids
Outline how prostaglandins are involved in the inflam response
Injury = autocoids and prostanoids released
= induced expression of COX 2
= aid synthesis of prostaglandins
= enhanced action of other autacoids (bradykinin and histamine) and potent vasodilator
How do prostaglandins enhance pain reception ?
Bind/activate GPCRs =
Increased neuronal sensitivity to bradykinin
Inhibition of K+ channels
Increased Na channels sensitivity
ALL = increased C fibre (carry pain impulses) activity
Explain how central nociception is sensitised
PGs active GPCR EP2 receptors =
Removes interneuronal inhibition = greater sensitivity to pain
What are the stages of pain?
1) sensitisation of peripheral pain fibres
2) long term pain then causes increased pain perception
Outline the role of each prostaglandin receptor
EP 1 = sensitising peripheral pain by increasing C fibre activity
EP 2 = increase vasodilation, sensitising central pain by inhib of inhibitory interneurons
EP 3 = increased heat production and decreased heat loss
What are the general therapeutic effects of NSAIDs?
Anti inflam = rheumatoid, osteoarthritis
Analgesics = mild/moderate pain
Antipyretics
What ADRs are associated with NSAIDs
COX 1 inhib = many side effects
Elderly long term use = iatrogenic morbidity/mortality
GI = pain, nausea, heartburn, gastric bleeding, ulceration (offset with PPIs)
Renal = decreased GFR
Vascular = increased risk of bleeding
Hypersensitivity = rashes, bronchial asthma