NSAID & Non-Opioid Analgesics

Question 1

What is the cause of chronic inflammation?

Answer 1

WBC infiltration of the tissue in response to acute inflammation.

Question 2

What inflammatory mediators, released by WBCs, are involved in a chronic inflammatory response?

Answer 2

Interleukins
GM-CSF
TNF
Interferons
PDGF

Question 3

What is the most important autocoid involved in acute inflammation?

Answer 3

Prostaglandin

Question 4

What is the main pathway target when using NSAIDs?
What is the secondary pathway?

Answer 4

COX pathway
LOX pathway

Question 5

Differentiate COX-1 & COX-2.

Answer 5

COX1 - Constitutive “always on”
COX2 - Stimulus dependent, inflammatory response.

Question 6

How does COX inhibition lead to gastric irritation?

Answer 6

COX1 inhibition = less constitutive PG synthesis = less gastric mucus production.

Question 7

What portion of the aspirin molecule binds to COX-1?
Where does it bind to?
Is this reversible?

Answer 7

Acetyl group
Serine group of COX1 molecule
The binding is irreversible.

Question 8

metabolism of aspirin?

Answer 8

Very metabolized
- Phase I by CYP450s
- Phase II by UGTs

Question 9

How do NSAIDs treat headaches?

Answer 9

Decrease sensitivity of brain vessels to bradykinin & histamine = CNS vasoconstriction.

Question 10

Which NSAID irreversibly blocks COX-1, thus preventing platelet aggregation?
How long will this platelet inhibition last?

Answer 10

Aspirin
8-10 days (the lifespan of the platelet)

Question 11

Which NSAID is COX-1 selective?
Which NSAID is COX-2 selective?

Answer 11

Aspirin
Celecoxib

Question 12

Which NSAIDs block COX-1 & COX-2 with equal efficacy?

Answer 12

Ibuprofen
Toradol
Meclofenamate

Question 13

Which NSAIDs are both COX & LOX inhibitors?

Answer 13

Indomethacin
Diclofenac

Question 14

What are the three areas of toxicity/irritation seen with NSAID use?

Answer 14

Gastric irritation (variable)
Nephrotoxicity
Hepatotoxicity

Question 15

How was aspirin extracted prior to modern medicine?

Answer 15

Willow Bark extraction

Question 16

How does aspirin treat fevers?

Answer 16

Direct peripheral vasodilation

Question 17

What is the primary use of aspirin?

Answer 17

Clot prevention (81-325mg day)

Question 18

What cancer has aspirin recently been show to decrease incidence of?

Answer 18

Colon cancer

Question 19

What is the primary adverse effect of aspirin?
Why does this occur?

Answer 19

GI upset
Weak acid so it upsets stomach, & inhibition of PG mucus production.

Question 20

What is the benefit of enteric coated aspirin?
How would this affect PG inhibition?

Answer 20

Skips weak acid effects upsetting stomach.
PG still inhibited.

Question 21

What can occur with chronic use of COX-2 selective agents?

Answer 21

Thrombosis from ↑ PLT aggregation

Question 22

How can prostaglandin inhibition affect pregnancy (specifically labor) ?

Answer 22

PG’s needed for labor (NSAIDs bad for pregnancy)

Question 23

Why is aspirin not given to children (especially after a viral illness)?

Answer 23

Reye Syndrome (hepatic injury & encephalopathy)

Question 24

What things are given for aspirin toxicity?

Answer 24

Activated Charcoal
Bicarb & IV fluids
Dialysis

Question 25

What symptom are hallmarks of moderate salicylate poisoning?

Answer 25

Tinnitus & fever

Question 26

What are the uses of Celecoxib? What allergy would preclude the use of celecoxib? How expensive is celecoxib?

Answer 26

Rheumatoid/Osteo arthritis & ulcer reduction Sulfonamide allergy Very expensive

Question 27

Adverse cardiovascular events are related to all NSAIDs except ________.

Answer 27

aspirin

Question 28

What black box warning exists for celecoxib?

Answer 28

Cardiovascular events due to PGI₂ inhibition (PGI₂ decreases plt aggregation)

Question 29

What drug can be given with Diclofenac to decrease its adverse GI effect profile? Why is this?

Answer 29

Misoprostol (Cytotec) Misoprostol is a synthetic PG

Question 30

What rare adverse effects can occur from chronic, high doses of ibuprofen?

Answer 30

Agranulocytosis Aplastic Anemia

Question 31

What are Indomethacin’s uses?

Answer 31

Patent Ductus Arteriosus (PDA) Rheumatism Gout

Question 32

What might indomethacin inhibit in addition to COX? What would be the result of this?

Answer 32

Phospholipase A & C ↓ WBC

Question 33

What is PDA (Patent Ductus Arteriosus)? What drug could be used for his prior to surgery? Why?

Answer 33

Shunt between Aorta & pulmonary veins in fetu. Indomethacin PG keep the shunt open; PG inhibition should close it.

Question 34

What NSAID is a potent pain reliever used in a lot of sports medicine programs? Can this NSAID help lower opioid usage?

Answer 34

Toradol (Ketorolac) Yes, 25-50% reduction in opioid usage.

Question 35

What is Acetaminophen’s mechanism of action? Does acetaminophen have antiinflammatory properties?

Answer 35

COX-2 inhibition (primarily CNS) pain signaling. No anti-inflammatory effects.

Question 36

Fatal doses of acetaminophen are associated with failure of what organs?

Answer 36

Liver (hepatotoxicity) Kidney (acute renal tubular necrosis)

Question 37

What is the primary path of metabolism of acetaminophen? How is it metabolized with higher doses?

Answer 37

Phase II primarily Switches to Phase I with higher doses.

Question 38

When would the selection of COX-2 selective drug make the most sense?

Answer 38

When the patient is at high risk for GI bleeds.

Question 39

What is the primary short-term use of glucocorticoid?

Answer 39

Suppression of Inflammation

Question 40

What are the adverse effects of chronic glucocorticoid usage?

Answer 40

Immunosuppression DM, obesity, muscle wasting Depression HTN

Question 41

What is the general mechanism of action of glucocorticoids in regards to blocking the immune response?

Answer 41

Inhibition of immune response by blocking transcription/translation.

Question 42

Glucocorticoids upregulate Annexin-1; what does Annexin-1 do?

Answer 42

Phospholipase A2 suppression (↓ AA) ↓ WBCs

Question 43

What three molecules increase due to translation when glucocorticoids are administered?

Answer 43

Annexin-1 Secretory Leukoprotease Inhibitors IL-10 (immunosuppressant)

Question 44

What inflammatory cytokine is inhibited by glucocorticoids?

Answer 44

NFkappaB

Question 45

What two primary indications for glucocorticoids were discussed in lecture?

Answer 45

Inflammation suppression Fetal Lung Maturation (↑ surfactant production)

Question 46

What are immune complexes? What disease do these occur in? Explain the sequence for immune complex formation. Where do these immune complexes end up at?

Answer 46

Chains of antibodies strung together Rheumatoid Arthritis. Rheumatoid antibodies are created & bind to “good” antibodies creating immune complexes. Joints (WBCs follow)

Question 47

What lab tests measure Rheumatoid Arthritis?

Answer 47

Sed rate C-Reactive Protein Rheumatoid Factor (measures immune complexes)

Question 48

Non-biologic DMARDs (disease-modifying anti-rheumatic drugs) are useful for what? Name the three mentioned in lecture.

Answer 48

Immunosuppression (non-specific) 1. Methotrexate (anticancer, ↓ dose for RA) 2. Cyclophosphamide 3. Cyclosporine

Question 49

Biologic DMARDs (disease-modifying anti-rheumatic drugs) are different from non-biologics how?

Answer 49

Very specific (block specific things in inflammation response)

Question 50

meloxicam target and adverse?

Answer 50

COX 2 selective inhibitor and less effective than celebrex

Question 51

Rituximab

Answer 51

DMARDs (disease modifying anti-rheumatic drugs) biologic DMARDs that depletes B-lymphocytes

Question 52

Biologic DMARDs

Answer 52

Abatacept (orencia) - blocks t-cell activation rituximab (ritixan) - depletes b-lymphocytes adalimumab (humira) - anti-TNF-alpha