Flashcards in NSAIDs - Fitz Deck (27)
Drug classes (w/ members) that target COX (7 total drugs)
For what injury type?
- Salicylates (Aspirin, Diflunisal)
- NSAIDs (Ibuprofen, Naproxen, Indomethacin, Diclofenac, Ketorolac)
- Coxibs (Celecoxib)
Name the PG associated w/...
- Renal artery
- Blood vessels
Uterus = PGF2a, PGE2 (contract)
Stomach = PGE2 (protection)
Renal aa = PGE2 (patency)
Vessels = PGI2 (dilation)
Platelets = TxA2 (aggregate)
CNS = PGE2 (fever)
PNS = PGE2 (pain sensitization)
Salicylate - side effect
4 similarities btwn COX-1 and COX-2
- Same substrate (AA)
- Same product (PGH2)
- Anti-inflammation effect
- Renal artery constriction effect
Ibuprofen vs. Naproxen
Ibuprofen = 2 hr half life
Naproxen = 14 hr half life
Indications for NSAIDs
- Gout FLARE
- Ankylosing spondylitis
Side effects of NSAIDs
GI ulcer (no PGE2)
Bleeding (no TxA2)
Peripheral edema, increased BP (renal artery constriction)
***People to be careful about when prescribing an NSAID
- HF or risk factors for HF
- Obesity, high LDL, etc.
- Renal disease
- BP medication
- Those at risk of infection (will blunt the fever response)
Contraindications for NSAIDs
- GI inflammation (gastritis, colitis, pancreatitis, hepatitis)
Celecoxib - MoA
COX-2 selective inhibitor
Celecoxib - benefit
Gastric-sparing (no ulcers)
Drugs that are more COX-1 selective (from most to least) (5)
Drug that acts on COX-1 and COX-2 equally
Drugs that are more COX-2 selective (2)
***Which drug is the only NSAID available for parenteral administration?
Where is it on the COX1/COX2 scale?
1000x COX-1 specific (most of all of them)
**Which side effect is shared by traditional NSAIDs and Celecoxib?
Peripheral edema, HTN (Renal artery constriction)
Patient has sulfa allergy. Which NSAID is contraindicated?
Celecoxib (sulfa drug) - SJS/TEN
What is high dose of Aspirin?
Pro-drug of Salicylate (converted in the liver)
***Side effects of Salicylate (or Aspirin) - COX independent (4)
**Acid-Base disturbance (respiratory alkalosis --> metabolic acidosis)
*Reye's syndrome (when treating viral infection)
Effect/Side effect of Aspirin at...
- 80-160 mg
- 325 mg - 1 g
- 1-6 g
- 6-20 g
- > 20 g
- Analgesic, ant-pyretic, anti-inflammatory
- **Acid-base issue
- **Shock, coma
Describe COX-independent side effects of Salicylate
Uncouples OxPhos, respiratory centers see low ATP, get hyperventilation, respiratory alkalosis causes bicarb wasting, accumulate acids b/c no ATP, get metabolic acidosis
Children w/ fever (viral illnesses, etc)...treatment?
Prevent risk of Reye's syndrome
******What is low-dose Aspirin used for? Why/how?
Anti-thrombotic (heart dz)
ASA (before conversion to salicylate) is an IRREVERSIBLE inhibitor of COX. Aspirin sits in portal vein (prior to liver) and acts on all the platelets, causing COX inhibition. Platelets have no nucleus, so they cannot make more COX. Hence they are permanently inactive
How long does it take to get full anti-thrombotic effect of low-dose aspirin?
How long will clotting ability return to normal after stopping low-dose aspirin?
When is Aspirin given as an anti-thrombotic agent? Why then?
After an MI (improves survival)
Before = GI bleeding, etc.
Why were the stronger Coxibs taken off of the market?
COX-2 can sometimes have a protective/beneficial effect in inflammation by making PGI2/prostacyclin (ex. atherosclerosis). Inhibiting COX-2 only allows COX-1 to dominate, leading to higher risk for CV disease (thrombosis).