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
What are the monitoring requirements for patients on NSAIDs?
LFTs, Creatinine/BUN, Stool Guaiac, CBC (CBC for possible blood dyscrasia)
What are the BEERs criteria?
Criteria to avoid use of NSAID in geriatric medicine, especially Indomethacin
Compare and contrast Aspirin and Acetaminophen. (MOA and ADEs)
1) Aspirin inhibits peripheral COX - Acetaminophen works on CNS COX
2) Aspirin has GI, Hepatic, and Renal Tox along with acid/base imbalance, and uricemia so monitor LFT, Cr/BUN, Guaiac, and Serum Salicyate - Acetaminophen pretty much only has liver failure from buildup of toxic metabolite
What does COX1 inhibition lead to?
Inhibition of platelets, increased bleed time, increased GI tox
What does COX2 inhibition lead to?
Anti-inflammation, pyretic, analgesic, increased BP, decreased urinary PGI2/TCA2 metabolites (Sometimes increased GI tox)
What is the MOA of aspirin?
Cox 1, Enteric coating available
What is a special ADE of aspirin?
Reyes syndrome (aspirin + varicella)
What additional monitoring must you do for aspirin?
Serum salicylate
What is the MOA of indomethacin?
Cox 1, Oral/Rectal
What is the MOA of Ketorolac?
Cox 1, Oral/Rectal
What is special about the elimination of Ketorolac?
It is mostly unchanged in urine
What ADE is most likely in Ketolorac?
It has the highest GI risk
What is the MOA of acetaminophen?
Nonspecific Cox 1 and 2 inhibitor in the CNS; it is NOT an antiinflammatory, Oral/IV
What is the MOA of Ibuprofen?
Nonspecific Cox 1 and 2
What is the ADE if ibuprofen?
It actually has the lowest GI risk of NS NSAIDs and safest for hepatotoxicity
What is the MOA of Ketoprofen?
Nonspecific
What is the MOA of Naproxen and what is the half life?
NS and Long
What is the MOA of Piroxicam and what is the half life?
NS and 60 hrs
What is the ADE with piroxicam?
Increased HTN w/ ACEi/ARB treatment
What is the MOA of Sulindac?
NS
What is the ADE of Sulindac?
5-10x risk of Hepatotoxicity (especially monitor LFT)
What is the MOA of Diclofenac and what is the half life?
Cox2/NS and 1 hr
What is given with Diclofenac to limit gastric ulcers?
Misoprostol
What is the ADE of Diclofenac?
Increased HTC w/ ACEi/ARB treatment
What is the MOA of Celecoxib?
it is THE COX2 inhibitor
What is the ADE of Celecoxib?
It has the lowest GI tox risk
