NSAIDs and DMARDs Flashcards
Function of aspirin
Acetylates and IRREVERSIBLY inhibits both Cox-1 and Cox-2, thus stopping arachidonic acid from turning to prostaglandins.
It increases bleeding time, but does not affect PT/PTT
Side effects of Aspirin
- Gastric Ulceration
- Bleeding
- Hyperventilation
- Reye Syndrome
- Tinnitus
Mechanism of NSAIDs
REVERSIBLY inhibit both Cox-s to stop Arachidonic acid from turning into prostaglandins or thromboxanes
Where are Cox-1 and Cox-2 expressed?
Cox-1 is expressed in most tissues, including platelets
Cox-2 is induced in inflammatory cells upon activation
What is the difference between prostaglandins and thromboxanes?
PGs increase uterine tone, but decrease vascular and bronchial tone
Thromboxanes just increase stuff: Platelet aggregation, Vascular tone, bronchial tone
Motrin/Naproxen vs Celecoxib
Motrin and Naproxen are non selective, but Celecoxib is a COX-2 inhibitor
Advantages of Celecoxib
Spares the gastric mucosa from the corrosive effects of COX-1 inhibition.
We use them for chronic conditions of inflammation
Acetaminophen function
REVERSIBLY and WEAKLY inhibits both coxes and is peripherally inactivated with most effects centered in the CNS. It has no effect on inflammation,
Side effects of Acetaminophen
Significant hepatic necrosis can occur with high doses, as hepatic metabolism of acetaminophen depletes glutathione supplies needed for their antioxidant properties.
Liver damage can be prevented if N-acetylcysteine or methionine are given since they regenerate glutathione
Mechanism of glucocorticoids
These guys are effective anti-inflammatories because they go up higher in the chain than even arachidonic acid by hitting phospholipase A2 (lowering AA levels).
Also inhibits NF-kb signaling which is important for Cox-2 signaling
Problem with glucocorticoids
Lots of side effects
- obesity
- Cushings
- diabetes
- osteoporosis
- immune suppression
- anxiety/psychosis
Discuss the metabolism of acetaminophen and why alcohol is a bad thing to take with it
Acetaminophen breaks down into gluconoride and sulfate ester normally, but in the presence of CYP2E1, it can break down to NAPQI, which can either conjugate harmlessly or cause hepatotoxins.
Alcohol stimulates CYP2E1.
What does Prostacyclin do and where does it come from
It, like Thromboxane and prostaglandins, is a downstream target for Cox. When we give motrin we also inhibit this guy, which normally vasodilates to keep vessels open.
Stopping this thing isn’t bad if thromboxane is also being reduced, because you don’t need dilated vessels if platelets aren’t aggregating.
What does low dose aspirin do?
Low dose aspirin hits Cox1 more than Cox2. This causes little platelet aggregation since we are knocking out thromboxane, but allows vasodilation from prostacyclin (Cox2) to remain active.
What is the problem with using our lovely Celecoxib?
As a Cox-2 inhibitor only, it stops vasodilation without stopping platelet aggregation, so we get plaques and occlusions.
That’s why this drug is linked to vascular concerns and heart issues.
