Flashcards in NSAIDs Deck (33)
What 3 sx do NSAIDs treat?
Fever, pain, inflammation
Explain ASA's mech of action.
How do other NSAIDs act?
- Covalently attaches an acetyl group to the active site of COX enzymes, irreversibly inhibiting COX-1.
- Also acetylates COX-2, but the active site of COX-2 is larger/more flexible, so arachidonic acid can access active site
Other than Aspirin, all other NSAIDs competitively inhibit COX enzyme activity blocking access of arachidonic acid to the active site.
What is the pattern of expression for COX-1 vs. COX-2?
- COX-1: Constitutively expressed (housekeeping)
- COX-2: inducible isoform
In what cell types is COX-2 induced?
In what tissue types is it constitutive expressed?
- Induced in macrophages, fibroblasts, synoviocytes
- Constitutive in kidney, brain, and endothelium
What is the affect of ASA on platelets? (name the molecule it acts on)
What is the appropriate dose (relative)?
- Anti-thrombotic (blocks pro-thrombotic thromboxane A2 AKA TXA2)
- Low dose
Is prostatcyclin pro- or anti-thrombotic?
Why doesn't ASA affect it?
- COX-1 is resynthesized in the endothelium, so low-dose aspirin does not effectively inhibit the production of anti-thrombotic prostacyclins
(prostatcyclin = PGI2)
Which NSAID has a rapid onset of action, and is ideal for fever and acute pain?
Which NSAID has a rapid onset of action, a long serum half-life 14hrs, twice daily dosing?
Which NSAID has a long serum half life- 50-60 hrs; once daily dosing?
Which NSAID is a potent anti-inflammatory, > toxicity; used to close patent ductus arteriosus?
Which NSAID is relatively selective for COX-2 and is associated with increased risk of MI/stroke?
Which NSAID is mainly used as IV analgesic as a replacement for opioid analgesics?
What are the 2 primary adverse affects of tNSAIDs?
Affects of GI/stomach, as well as kidneys
The stomach and GI disturbances caused by Aspirin and traditional NSAIDs are due to the inhibition of ________ , which is responsible for the production of PGs that act to prevent damage to gastric and intestinal epithelial cells caused by gastric acid and digestive enzymes.
COX-2 inhibitors are no more efficacious than other NSAIDs, but might be preferable in patients with
a prior history of ____________.
NSAID contraindications include: (5)
(include +3 that are specific contraindications for ASA)
GI ulcers, bleeding disorders, renal disorders (elderly), pregnant, increased risk for CV dz
ASA: previous hypersensitivity to ASA, children w/febrile viral infections (can induce Reyes syndrome). ASA: gout (inhibits uric acid secretions at low doses)
Does acetaminophen inhibit COX-1 or COX-2 in periphery? CNS?
- Neither in periphery
- COX-2 in CNS
*Which of the following effects does acetaminophen have?
YES: a) Anti-pyrretic + d) Analgesia
NO: b) Anti-inflammatory + c) Anti-platelet
Would hemophiliacs need to avoid tNSAIDs and celecoxib?
Yes - tNSAIDs
No - CBX (anti-platelet COX-1 spared)
Acetaminophen OD results in the build up of the toxic metabolite ____________, which depletes hepatic ___________.
- NAPQI (N-acetyl benzoquinoneimine)
___________ is used as an antidote to acetaminophen OD because it replenishes endogenous glutathione levels.
Name 3 drugs that interact w/all NSAIDs to decrease renal clearance and cause toxicity from that drug.
Lithium, methotrexate, aminoglycosides
Why don't you want to combine low dose ASA w/NSAIDs (except CBX)?
NSAIDs antagonize the beneficial effects of low-dose ASA.
Combining NSAIDs w/ ______________ (like ______) increase the risk of bleeding.
Oral anti-coagulants (like warfarin)
Combining NSAIDs w/ ______________ (like ______) can counteract the anti-hypertensive effects of the drug.
Anti-hypertensives (ACE inhibitors, beta blockers)
What is the problem w/combining oral hypoglycemics (e.g. sulfanylureas) w/ASA?
Potentiate hypoglycemic effects of sulfonylureas.
What is the problem w/diuretic agents (e.g. furosemide) w/NSAIDs?
NSAIDs promote Na+ and H2O retention.
Which drugs should not be combined w/ASA, and which shouldn't be combined w/any NSAID or NSAIDs except CBX?
ASA: Oral hypoglycemics (sulfonylureas)
NSAIDs: Oral anti-coagulants (e.g. warfarin), anti-hypertensives (ACE inhibitors/beta-blockers), Li, methotrexate, aminoglycosides (e.g. gentamicin), diuretic agents (e.g. furosemide).
NSAIDs except CBX: *low-dose ASA
*Which of the following can a pt w/Reyes syndrome safely use? (which is preferable?)
All except ASA (acetaminophen preferable)
Regarding thromboxane A2 and PGI2, why does CBX increase CVD risk compared to low dose ASA?
Low dose ASA inhibits pro-thrombotic TXA2 while sparing anti-thrombotic PGI2. (=
CBX inhibits anti-thrombotic PGI2 while sparing pro-thrombotic TXA2. )=
What is acetaminophen metabolized into?
What does this do besides working w/the drug to inhibit CNS COX-2?
- Also stimulates cannabinoid receptors
What drug would be indicates for pts with a fever but also CVD?