NSAIDs Flashcards
What are the major advantages of NSAIDs?
They are all oral, some extended release, they are used to treat pain from inflammation,a nd they are cheap.
Describe how NSAIDs achieve pain relief.
They reversibly inhibit (except for Aspirin, which irreversibly inhibits) the COX pathway, COX 1 = constitutive, COX 2 = inducible
COX inhibition can lead to what if chronically used?
Adverse side effects; specifically increased risk of CV and GI tox
How are NSAID’s metabolized and eliminated?
They are hepatically metabolized and renally eliminated except for ketorolac, it is mostly unchanged in urine
What are the major GI toxicity risk factors with NSAID’s?
> 55 y/o, male, Hx of GI oroblems, prolonged NSAID use, max dosage, H. pylori infection, alcohol, smoking, use with anticoagulants, corticosteroids, SSRIs and SSNRI’s and chronic disease
What effect does increased half life have on GI toxicity?
Generally the higher the half life = more GI tox due to accumulation
How do you reduce GI tox with NSAIDs?
Take with food (caution not to take more if immediate effect not seen), give with PPI, prostanoid, or H2 receptor antagonist.
If an NSAID is given with a PPI for reduced GI tox, what must the patient be aware of?
PPIs decrease stomach pH and may affect oral drug absorption
What are the most common CV AE’s with NSAIDs? What are they thought to be due to?
MI, CHF, and HTN; May be due to a dysregulation of PGI2/TXA2 and COX selectivity is not the only factor
What is the MOA of aspirin? (in regards to platelets)
It irreversibly acetylates COX1 in platelets leading to inability to make TXA2; new platelets must be synthesized to overcome this
What happens when an NSAID inhibits Aspirins MOA?
It increases the relative CV risk by competitive inhibition of the action of Aspirin, shifting the balance toward a pro-aggregatory condition and adverse CV effects. (i.e. Ibuprofen inhibiting aspirins effect)
What adverse effect is seen with Diclofenac and Piroxicam? How does it occur?
Increased BP w/ ACEi and ARBs in treatment for HTN; occurs through decreased PGI2 production
In what NSAID is hepatotoxicity incidence higher than the rest?
Sulindac; can occur with all especially w/ alcohol use
What role does PG play in renal function when a patient has renal disease, vasoconstrictor therapy, volume depletion, HF, or cirrhosis?
PG maintains GFR and RBF in those disease states
What can NSAIDs do to PG? what does this lead to?
They can limit PGI2 production leading to AKI/ATN can be with initial nephrotic or nephritic syndrome and can occur with ANY NSAID
What happens to clearance of lithium/MTX with NSAIDs?
They are decreased
