Flashcards in NSAIDs Deck (47):
What are the drug classes for treatment for RA?
Note that both classical and biological DMARDs possess the ability to slow progression of the disease process, an attribute that is not evident with NSAIDs.
Is acetaminophen (tylenol) used for RA?
No, even though it is an NSAID, it provides no anti-inflammatory
action (only relief of pain and fever)
Doesn't change course of disease
What NSAIDs can be used for RA?
-Aspirin (acetyl-salicyclic acid)
-Ibuprofen (Motrin, Advil)
-Naproxen, Ketoprofen, Piroxicam
What is unique about Celecoxib?
Cox-2 specific drug
T or F. NSAID action on COX is reversible
T, except in aspirin
What is different between expression of COX-1 and COX-2?
COX-1 is constitutive and COX-2 is inducible
How are most NSAIDs metabolized?
extensive hepatic metabolism with predominant elimination in the urine and some in feces
What NSAID is noticably metabolized differently?
Ketorolac (58% unchanged in urine) and little in feces
What prostaglandin in particular is involved in activation of inflammatory cells?
What happens following tissue damage?
mast cells and macrophages are activated and some blood-borne immune cells, including neutrophils may be recruited. Various immune mediators, such as TNF-a, IL-1B, IL-6, and others are released which exert their allegoric effects by a ting directly on nociceptors or indirectly through the release of prostanoids
What are the effects of COX-2 inhibition?
-reduced urinary PGI2 metabolites
thus, these effects are seen in ALL NSAIDs
What are the effects of COX-1 inhibition?
-reduce urinary TXA2
-inhibit platelet activity and increase bleeding time
GI toxicity is related to inhibition of which COX enzyme?
What 'traditional' NSAIDs have a propensity for COX-2 over COX-1?
What 'traditional' NSAIDs have a propensity for COX-1 over COX-2?
How does chronic NSAID consumption lead to gastric damage and bleeding?
Not only is there direct chemical irritation of the mucosal tissue but the inhibition of PGE2 interrupts essential cytoprotective mechanisms in the stomach involving mucus secretion, bicarbonate release and the initiation of essential repair processes in underlying tissue.
What are some risk factors for GI bleeding with NSAIDs?
-older age (risk doubles ever decade over 55)
-CV disease, HTN, diabetes, hepatic or renal impairment
Other risk factors for GI bleeding with NSAIDs?
-helicobacter pylori infection
-excessive alcohol use
What concurrent meds can increase risk of GI bleed with NSAIDs?
-venlafaxine or duloxetine
What are some ways to reduce GI bleed risk with NSAIDs?
-enteric coating (doesn't eliminate)
-MAYBE advocate taking NSAIDs on an empty stomach to achieve faster onset of action and avoid 'extra' doses because relief isn't met fast enough by the patient
Other ways to reduce GI bleed risk with NSAIDs?
-co-administer prostaglandin analogue misoprostol, or more usually these days an H2 receptor antagonist or proton pump inhibitor.
What is the benefit of PPIs with NSAIDs?
possesses superior effectiveness due to the more complete suppression of acid
secretion, a mechanism-based issue (just as good as a COX-2)
What should be considered when giving a PPI with an NSAID?
-PPIs can alter the efficacy of concurrent drugs that rely on stomach acidity for absorption
Contraindications of PPIs?
concurrent with cloidogrel
What NSAID will not change the balance between TXA2 and PGI2, and thus lower CV exacerbation risk?
ibuprofen because it doesn't have an increased affinity for COX-1 or COX-2
What is another potential thing to consider with a COX-2 inhibitor?
promotes shift toward TXA2 production from COX-1 and thus a pro-thrombotic state
T or F. High doses of ibuprofen is associated with increased risk of vascular events
T. Even though it is COX neutral.
High dose of what NSAID is not associated with increased CV related (thrombo-forming) risk?
What is the major difference between NSAIDs and aspirin?
aspirin irreversibly inhibits the COX enzyme by acetylating it.
DD interaction of aspirin?
There is a real potential for concurrent administration of NSAIDs to inhibit the ability of low-dose aspirin to reach its binding site in the platelet and to provide irreversible enzyme inhibition in prophylaxis of MI.
Since the traditional NSAID action is reversible, there is a potential for antiplatelet activity to be lost and increased cardiovascular risk to occur.
Which NSAID has the highest risk of hepatotoxicity?
Sulindac (via hypersensitivity mechanism)
What is the role of PGE2 and PGI2 at the kidneys?
Prostaglandin I2 and E2 play an important role in micro-regulation of perfusion in renal tissue, most especially in abnormal “stress” situations where they help to maintain GFR.
**and NSAIDS can block this!!***
What is the effect of chronic NSAID use by blocking PGE2 and PGI2?
reversible renal ischemia, reduced glomerular hydraulic pressure and reduced GFR
NSAIDs decrease the clearance of what drugs?
lithium and methotrexate
T or F. NSAIDs can
antagonize the effects of
Recommended patient monitoring with chronic NSAID use
Why get CBC with chronic NSAID use?
NSAIDs can rarely cause various blood dyscrasia
Chronic aspirin therapy may warrant monitoring of _______
What does overdose of salicylate cause?
capable of passing across the BBB where it stimulates the respiratory centre, resulting in respiratory alkalosis.
The metabolite also disrupts intermediary metabolism contributing to metabolic acidosis.
The picture is thus one of a mixed alkalosis/acidosis phenomenon;
How does salicylate overdose cause metabolic acidosis?
it causes uncoupling of oxidative phosphorylation and interruption of glucose and fatty acid metabolism
Death in salicylate overdose is most commonly due to what?
cerebral and pulmonary edema (via increased capillary permeability) lead to ultimate demise if the patient is not decontaminated.
Which NSAIDs should be avoided in elderly?
-Indomethacin (worst bleed risk)
all others should consider giving a PPI or misoprostol too
T or F. Acetaminophen (tylenol) has no peripheral action
T. Not anti-inflammatory (not an NSAID)
Acetaminophen (Tylenol) is most often associated with what AE?
acute hepatic failure
Why not add a prostaglandin antagonist with chronic NSAID use?
not as effective (short duration of action)- PPIs are irreversible which is why they are so effective
Which NSAID has the lowest CV risk?