Fitzy: Osteoarthritis and Joint Inflammation Pharmacology Flashcards
What analgesics are used for osteoarthritis?
- acetaminophen (non narcotic)
- Tamadol and codeine are narcotics
What anti inflammatory agents are used for osteoarthritis?
- NSADs
- gastric anti-secretory agent
- triamcinolone (corticosteroid
in the first step in pain relief in osteoarthritis, what do we use?
- acetaminophen
- … WITHOUT inflammation
is acetaminophen an anti inflammatory agent?
NO!
-it’s an analgesic and anti pyretic agent, but not an anti inlammatory agent
fun fact, what was the important thing about acetylsalicylic acid (aspirin)?
- it has irreversible inhibition of COX
- acetylates it
what actually is acetaminophen?
-acetyl-p-aminophenol
complications and risks from acetaminophen overdose?
-serious, potentially lethal liver toxicity
how will a person with liver toxicity present?
- ER
- emesis, jaundice, and altered mental status
What does acetaminophen get converted to that hurts us?
- NAPQI by CYP450, then that gets a glutathione group added onto it
- depletes glutathione content
- once we run out of GSH, then we can’t detoxify NAPQI and it reacts irreversibly with cell proteins
- Catastrophic cell damage
- CYP 450 does this
What histologic finding do we find from NAPQI toxicity?
- centrolobular necrosis
- the central part is where there is a lot of CYP 450… makes senseWhat i
what is the antidote for acetaminophen overdose?
- N-Acetylcysteine.. NAC
- it replenishes the GSH pool
- it also reacts directly with NAPQI to deactivate it… spares proteins and salvages cells
if acetaminophen doesn’t work for osteoarthritis, what do we go to next?
-NSAIDs!
What was the bolded drug on the NSAID list that is the only US NSAID in injectable formulation?
-Ketorolac
What should make us wear of treating this with an NSAId?
- GI risk
- CV risk
- Htn, atherosclerosis, smoking
- Hypersensitivity
How many NSAIDs should be used at once?
-one and only one
What is the exception to the one at a time rule?
- use of cardioprotective dose of aspirin with other NSAIDs
- Caution: low dose aspirin may increase the risk of upper GI bleeding in patients taking NSAIDs…. antithrombotic effects
If someone is having adverse effects to an NSAID, what do we switch on them?
-the CLASS of NSAIDs that they are taking
Is celecoxib safer for the GI tract?
- yes!
- remember they are only annoying for the renal arteries because they selectively inhibit COX2
What are potential complications attributed to Coxibs?
- Cardiovascular safety
- they spare COX1 so the platelets can still make TxA2
- endothelium can make PGI2… and that was on the other end of the hemostasis scale from TxA2..
- if we inhibit COX-2, TxA2»> PGI2
- even so, Celecoxib is the safest thing on the market
If the symptoms persist, worsen, and NSAIDs fail, what do we do?
- Intra-articular anti-inflammatory steroids
- Triamcinolone acetonide
- Triamcinolone hexonide
- limited systemic exposure; fewer side effects compared to systemic corticosteroids
What is the difference betwee NSAIDs and Triamcinolone?
- NSAIDs will inhibit COX-2 directly
- Triamcinolone will repress the OCS2 mRNA protein induction.. less COX2, less PGs formed… it just goes a step further back
What were the narcotic analgesics again?
- Tramadol
- Codeine
- use alone or combined with a cetaminophen and it’s only short term
What kind of receptor do the narcotics bind?
- Mu receptors
- they are Mu receptor agonists
- Morhpine, Codeine, Tramadol
What are the side effects of narcotics?
- increase smooth muscle tonen and inhibit the coordinated peristalsis required for propulsion, which contributes to nausea and vomiting as well as constipation
- constipation can be an intolerable side effect in some patients who need to take opioid (tramadol or codeine taken chronically)
Tramadol, what is it?
- Moderate Mu agonist
- N-desmethyl is the active metabolite
- analgesia-moderate pain
- inhibits catecholamine reuptake
What patients do we have to be cautious with when using tramadol?
-patients on tricyclic, or SRI anti-depressants
What nasty side effect is associated with Tramadol?
-seizures
