8. NSAIDs Flashcards
Name the prostanoids
Prostaglandins
Prostacyclin
Thromboxane
What are the homeostatic functions of COX-1?
GI protection (acid and mucus)
Platelet aggregation
Vascular resistance
What are the homeostatic functions of COX-2?
Renal homeostasis
Tissue repair and healing
Reproduction (uterine contractions)
Inhibition of platelet aggregation
What are the pathological functions of COX-1?
Chronic inflammation
Chronic pain
Raised BP
What are the pathological functions of COX-2?
Chronic inflammation
Chronic pain
Fever
Blood vessel permeability
What is the common mode of action of NSAIDs?
Inhibition of COX
Decrease prostaglandin, prostacyclin and thromboxane synthesis
Compete with arachnoid acid for hydrophobic site of COX enzymes
How does inhibition of COX cause analgesic effects?
Reduces peripheral pain fibre sensitivity by blocking PGE2
How do NSAIDs reduce inflammation?
Reduce production of prostaglandins released at site of injury
Therefore there is less vasodilation and oedema
How do NSAIDs reduce body temperature?
Inhibition of hypothalamic COX-2 where cytokines induced prostaglandin synthesis is elevated results in a reduction in temperature
What are the GI ADR?
Dyspepsia
Nausea
Peptic ulceration, bleeding and perforation
Exacerbation of IBD
Why are GI symptoms the most common ADR to NSAIDs?
Decrease mucus and bicarbonate secretion, increase acid production
Decrease mucosal blood flow, leads to enhances cytotoxicity and hypoxia
What are the contraindications of NSAIDs?
Elderly Prolonged use Smoking Alcohol History of peptic ulceration H.pylori CKD Heart failure
What are the DDI of NSAIDs?
Aspirin Glucocorticosteroids Anticoagulants ACEi ARBs Diuretics
What are the renal considerations of NSAIDs?
NSAIDs produce reversible decrease in GFR and renal blood flow
Prostaglandins inhibit sodium absorption in CD and NSAIDs inhibit this action therefore there is an increase in NA, H2O and BP
Name 2 selective COX-2 inhibitors
Celecoxib
Etoricoxib
What are the benefits of selective COX-2 inhibitors compared to other NSAIDs?
Fewer GI ADRs
When can selective COX-2 inhibitors be useful?
When monitored in severe osteo and rheumatoid arthritis for longer term treatment
What do all NSAIDs increase the risk of?
MI including in low risk people
What are the indications for NSAIDs?
Inflammatory conditions - joint and soft tissue
Osteoarthritis - not first line
Postoperative pain
Topical use on cornea
Menorrhagia
Low dose aspirin for platelet aggregation inhibition
Opioid sparing when used in combination
