NSAIDs Flashcards
Inflammation
Active response of tissues to injury (beneficial or harmful)
Processes involved in inflammation
Immune responses, coagulation cascade, regeneration and repair
4 changes involved in inflammation
Vasodilation, edema, WBCs enter tissue, pain
Fibrosis
Scarring as a result of chronic inflammation
Inciting causes of inflammation
Infection, trauma, necrosis, immune-mediated disease
Beneficial outcomes of inflammation
Eliminates agent, repairs + regenerates
Harmful outcomes of inflammation
Loss of function, systemic effects, scar formation
Synthesis of inflammatory mediators
Some synthesized in advance (histamine), some synthesized at the site (prostaglandins)
Redundancy of inflammatory mediators
Many trigger the same response
Major classes of pro-inflammatory mediators
Eicosanoids (prostaglandins, thromboxane, prostacyclin), leukotrienes
Non-pharmacological treatments of inflammation
Rest, heat/cold, weight reduction, surgery
Pharmacological treatments of inflammation
NSAIDs, glucocorticoids
Oldest NSAID
Aspirin
Mechanism of aspirin
Inhibits prostaglandin synthesis
Main benefits of NSAIDs
Anti-inflammatory, antipyretic, analgesic
Normal physiological roles of prostaglandins
Synthesized from arachidonic acid by COX enzymes
COX1
Housekeeping enzyme at lowlevels in all tissues; produces thromboxane, other prostaglandins, prostacyclins
COX2
Normally present at very low levels in most tissues, very important for homeostasis in some tissues
TXA2
Thromboxane, important for platelet aggregation
PGD2, PGE2
Prostaglandins synthesized by both cox enzymes; maintain blood flow and are involved in gastric mucosa protection
PGI2
Prostacyclin; inhibit platelet aggregation, vasodilate, and protect gastric mucosa
Prostaglandin roles during inflammation
COX2 is upregulated locally, causing the 5 main symptoms of inflammation
NSAIDs mechanism
Inhibit usually both COX1 and COX2
Major benefit of NSAIDs
Reduces blood flow to the site of injury
Adverse effects of NSAIDs
Inhibit normal protective effects of gastric mucosa (ulcers and bleeding), increased bleeding tendencies, renal medullary hypoxia and papillary necrosis
Pk of NSAIDs
Weak acids, bound to protein, hepatic metabolism, variable elimination
Adverse effects of NSAIDs
GI ulceration, increased bleeding, inhibition of uterine motility, decreased renal perfusion, renal necrosis in dehydrated patients
Contraindications of NSAIDs
Gi ulcers, renal disease, hepatic disorder. Hypoproteinemia, dehydration, cardiac disease, hypersensitivity, concurrent use
Clinical uses of NSAIDs
Relief of musculoskeletal and inflammatory pain
Mechanism of aspirin
Inhibits COX1 irreversibly, causing prolonged effects
Effective uses for aspirin
Musculoskeletal and cutaneous pain, not visceral
Adverse effects of aspirin
Bleeding, dose-dependent gastric ulceration, renal damage
Contraindications for aspirin
Bleeding disorders, prone to gi ulcers
Ibuprofen mechanism
Inhibits COX1 and COX2
Effective uses for ibuprofen
Arthritis and musculoskeletal pain
Adverse effects of ibuprofen
Gastric ulceration, myocardial infarction risk
Celoxicib mechanism
Selective for COX2
Effective uses of celecoxib
Osteoarthritis (not analgesia)
Benefits of celecoxib
Less likely to cause GI ulceration and bleeding
Adverse effects of celecoxib
Reduced renal function, increased risk of stroke and MI, concern with chronic use
How coxibs increase risk of stroke and MI
They only inhibit COX2, producing less PGI2 which prevents platelet aggregation, but doesn’t inhibit COX1 so thromboxane is not inhibit el
Acetaminophen
Inhibits central PG synthesis in the CNS, so it is only an antipyretic and analgesic
