NSAIDs Flashcards
What three things do NSAIDs treat?
Inflammation
Pain
Fever
Three types of NSAIDs
Aspirin/salicylates
Traditional NSAIDs
COX-2 specific inhibitors
Mechanism of action for NSAIDs
Inhibition of COX activity by preventing the production of prostaglandins
Are traditional NSAIDs selective?
No. They will bind both COX-1 and COX-2
How do NSAIDs inhibit COX enzymes?
Preventing the binding of the arachidonic acid substrate
Describe aspirin’s mechanism of action.
It covalently attaches an acetyl group to the active site of COX enzymes, irreversibly inhibiting COX-1 activity.
What is the difference between COX-1 and COX-2 inactivation with aspirin?
The active site of COX-2 is larger and more flexible, so arachidonic acid can still gain access to the active site. Less potent inhibitor of COX-2 than COX-1.
COX-1 is expressed how, and involved in what?
Constitutively expressed; involved in housekeeping functions
COX-2 is expressed where, and involved in what?
Mostly in macrophages, synoviocytes, and fibroblasts - is involved in the pro-inflammatory response.
Where is COX-2 constitutively expressed?
Kidney, brain, and endothelium.
Describe the effects of low-dose aspirin.
Effective anti-thrombotic agent because it pretty much exclusively effects the platelets since they cannot resynthesize their COX-1, but it is easily resynthesized elsewhere.
Key features of ibuprofen
Rapid onset, ideal for fever and acute pain
Key features of naproxen
Rapid onset of action, only twice daily dosing
Key features of oxaproxin
Long serum half-life, only once daily dosing
Key features of indomethacin
Potent anti-inflammatory, greater toxicity; used to close patent ductus arteriosus
Key features of diclofenac
Relatively selective for COX-2; associated with increased risk of MI/stroke
Key features of ketorolac
Mainly used as IV/IM analgesic as a replacement for opioids
Ten most affected organs
- GI/stomach
- Renal
- Cardiovascular
- Anti-platelet effects/increased bleeding
- Hypersensitivity
- CNS
- Skin
- Liver
- Photosensitivity
- Ductus arteriosus closure in pregnancy
Why do GI issues occur in NSAIDs?
Inhibition of COX-1, which inhibits prostaglandin formation responsible for preventing damage to gastric/intestinal epithelial cells
When are COX-2 inhibitors indicated?
Patients with a prior history of GI bleeds and/or ulcers
NSAIDs are contraindicated in what 8 cases?
- Patients with a GI ulcers
- Patients with bleeding disorders
- Patients with renal disorders (elderly)
- Patients with previous hypersensitivity
- Pregnant women
- Patients with increased risk of CVD
- Children with febrile viral infections
- Aspirin contraindicated in gout
Interaction between low-dose aspirin and NSAIDs
Antagonizes beneficial effects of low-dose aspirin by preventing binding of aspirin
Interaction between oral anti-coagulants and all NSAIDs
Increased risk of bleeding from platelet COX-1 inhibition
Interaction between anti-hypertensives and NSAIDs
Decreased ant-hypertensive effect; NSAIDs promote renal vasoconstriction
Interactions between diuretic agents and NSAIDs
Increased risk of high blood pressure between NSAID renal vasoconstriction and diuretic water/sodium retention
Interaction between diuretic agents and oral hypoglycemics
Potentiates hypoglycemic effect through protein binding competition
Why is it important not to use aspirin in viral illness in children?
Reye’s syndrome: fatal liver degenerative disease associated with encephalitis
How does acetaminophen work?
Metabolized selectively in the brain that inhibits COX-2 in the CNS, as well as act on the endogenous cannabinoid system in the pain and thermoregulatory centers of the CNS
What effects does acetaminophen NOT have?
Anti-inflammatory and anti-platelet activity (no peripheral activity)
Acetaminophen is the preferred analgesic in which patients?
- Have allergies to aspirin/salicylates
- Children with viral infections
- Patients with hemophilia/bleeding disorders
- Patients with prior history of gastric/peptic ulceres
Describe acetaminophen overdose.
Toxic build-up of metabolite N-acetylbenzoquinoneimine in the liver
What is used as an antidote for acetaminophen poisoning?
N-acetylcysteine; replenishes endogenous glutathione levels
