NSAIDs - Fitz

Question 1

Drug classes (w/ members) that target COX (7 total drugs)

For what injury type?

Answer 1

• Salicylates (Aspirin, Diflunisal)
• NSAIDs (Ibuprofen, Naproxen, Indomethacin, Diclofenac, Ketorolac)
• Coxibs (Celecoxib)

Tissue injury

Question 2

Name the PG associated w/…

• Uterus
• Stomach
• Renal artery
• Blood vessels
• Platelets
• CNS
• PNS

Answer 2

Uterus = PGF2a, PGE2 (contract)
Stomach = PGE2 (protection)
Renal aa = PGE2 (patency)
Vessels = PGI2 (dilation)
Platelets = TxA2 (aggregate)
CNS = PGE2 (fever)
PNS = PGE2 (pain sensitization)

Question 3

Salicylate - side effect

Answer 3

GI ulcers

Question 4

4 similarities btwn COX-1 and COX-2

Answer 4

• Same substrate (AA)
• Same product (PGH2)
• Anti-inflammation effect
• Renal artery constriction effect

Question 5

Ibuprofen vs. Naproxen

Answer 5

Ibuprofen = 2 hr half life
Naproxen = 14 hr half life

Question 6

Indications for NSAIDs

Answer 6

• Osteoarthritis
• Arthritides
• Bursitis
• Gout FLARE
• Ankylosing spondylitis
• Dysmenorrhea
• Headaches/Migraine

Question 7

Side effects of NSAIDs

Answer 7

GI ulcer (no PGE2)
Bleeding (no TxA2)
Peripheral edema, increased BP (renal artery constriction)

Question 8

***People to be careful about when prescribing an NSAID

Answer 8

• HF or risk factors for HF
  
  • Obesity, high LDL, etc.
• Renal disease
• BP medication
• Those at risk of infection (will blunt the fever response)

Question 9

Contraindications for NSAIDs

Answer 9

• Asthma

- GI inflammation (gastritis, colitis, pancreatitis, hepatitis)

Question 10

Celecoxib - MoA

Answer 10

COX-2 selective inhibitor

Question 11

Celecoxib - benefit

Answer 11

Gastric-sparing (no ulcers)

Question 12

Drugs that are more COX-1 selective (from most to least) (5)

Answer 12

Ketorolac
Indomethacin
Aspirin
Naproxen
Ibuprofen

Question 13

Drug that acts on COX-1 and COX-2 equally

Answer 13

Salicylate

Question 14

Drugs that are more COX-2 selective (2)

Answer 14

Celecoxib

Diclofenac

Question 15

***Which drug is the only NSAID available for parenteral administration?

Where is it on the COX1/COX2 scale?

Answer 15

Ketorolac

1000x COX-1 specific (most of all of them)

Question 16

**Which side effect is shared by traditional NSAIDs and Celecoxib?

Answer 16

Peripheral edema, HTN (Renal artery constriction)

Question 17

Patient has sulfa allergy. Which NSAID is contraindicated?

Answer 17

Celecoxib (sulfa drug) - SJS/TEN

Question 18

What is high dose of Aspirin?

Answer 18

Pro-drug of Salicylate (converted in the liver)

Question 19

***Side effects of Salicylate (or Aspirin) - COX independent (4)

Answer 19

**Acid-Base disturbance (respiratory alkalosis –> metabolic acidosis)
**Tinnitus
Hypersensitivity
*Reye’s syndrome (when treating viral infection)

Question 20

Effect/Side effect of Aspirin at…

• 80-160 mg
• 325 mg - 1 g
• 1-6 g
• 6-20 g
• > 20 g

Answer 20

• Anti-platelet
• Analgesic, ant-pyretic, anti-inflammatory
• **Tinnitus
• **Acid-base issue
• **Shock, coma

Question 21

Describe COX-independent side effects of Salicylate

Answer 21

Uncouples OxPhos, respiratory centers see low ATP, get hyperventilation, respiratory alkalosis causes bicarb wasting, accumulate acids b/c no ATP, get metabolic acidosis

Question 22

Children w/ fever (viral illnesses, etc)…treatment?

Why?

Answer 22

Acetaminophen (Tylenol)

Prevent risk of Reye’s syndrome

Question 23

****What is low-dose Aspirin used for? Why/how?

Answer 23

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

Question 24

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?

Answer 24

3 days

3 days

Question 25

When is Aspirin given as an anti-thrombotic agent? Why then?

Answer 25

After an MI (improves survival)

Before = GI bleeding, etc.

Question 26

Why were the stronger Coxibs taken off of the market?

Answer 26

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).

Question 27

Why was Celecoxib NOT taken off the market?

ALL NSAIDs have what?

Answer 27

Confers same level of CV risk as any NSAID

Black box warning for CV risks