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11 Cards in this Set
- Front
- Back
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Explain the Mechanism of Action of NSAIDS
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block cyclooxygenase
AA--(COX)-->PG Functions of PGs: 1. support renal function 2. support platelet function 3. protect gastric mucosa 4. inflammation and pain!! PGs also increase peripheral and central excitability Result: hyperalgesia and allodynia |
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Efficacy of NSAIDs
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all have similar efficacy
-anti-inflammatory -analgesic -anti-pyretic some are more/less potent, but at max dose - efficacy nearly the same |
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Adverse Effects
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1. Upper GI
- dose dependent toxicity - intolerability, dyspepsia, GI bleeding, ulcers 2. Renal - may cause renal failure (acute/chronic), fluid retention may cause heart failure (oedema, hypertension) 3. Anti-platelet -contribute to blood loss 4. Hypersensitivity - angioedema, bronchospasm |
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NSAID mortality
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Heaps of people use it
Heaps of people go to hospital for it Heaps of people die from it Usually GI bleeding |
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Coxibs
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Selective COX-2 inhibitors
COX-2 has bulky side pocket to fit drugs (Celecoxib) -Less GI bleeding -No platelet side effects (less blood loss) -Better for bone fractures -No bronchospasm in NSAID sensitive asthma |
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Types of NSAIDs
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Non-selective
1. Salicylates - aspirin 2. Arylpropionic acids - ibuprofen, naproxen 3. Penylacetic acids - diclofenac 4. "Oxicam's" (most harmful) - piroxicam COX-2 Selective - Celecoxib - Parecoxib |
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Gastroprotective strategies with NSAIDS
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NSAIDS + PPI = good
Celecoxib = better Celecoxib + PPI = best |
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COX-1 and COX-2 in the Kidney
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The kidney expresses both COX-1 and COX-2 constituitively
"If you withdraw NSAIDs due to renal toxicity, you shouldn't give COX-2 inhibitors either, as we assume they're the same renally" |
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COX-2 inhibitors and the CVS evidence
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"Fitzgerald Hypothesis"
aspirin - acts on thromboxane - lowers CV events coxib - acts on prostacyclin - increases CV events BUT... jumbled data Unclear whether COX-2 inhibitors have greater CVS risk (But Rofecoxib was and hence, removed) |
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COX-1 and COX-2 selectivity vs. CVS and GIT side effects
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NSAIDS - both increased risk with increased dose
Coxibs - both increased risk with increased dose BUT slope of CVS risk much higher than GI slope In Aus - our Coxibs (Celecoxib and Parecoxib) are better than NSAIDs for both CVS and GIT effects |
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Aspirin
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Unique activity on COX in platelets
- irreversible blockade Unique toxicity - Reye's syndrome: fluminant hepatic failure & death in kids who took the aspirin for fever in acute viral illness - Particular risk of bronchospasm Aspirin OD - Acidosis -> respiratory depression - fever - renal failure - high mortality |
