Inflammation

Question 1

What was the origin of aspirin? What is its effect?

Answer 1

Willow bark isolate; COX1/2 non-selective inhibitor

Question 2

What is the target of NSAIDs?

Answer 2

COX 1 and COX 2

Question 3

How many classes of NSAID are we looking at (there are more)?

Answer 3

Seven

Question 4

What is the mechanism of aspirin’s action on COX?

Answer 4

Irreversible inhibtion via acetylation

Question 5

What is the effect of acetylsalicylate’s byproduct following COX inhibition?

Answer 5

The remaining salicylate has a 30 minute half life as a competitive inhibitor

Question 6

What are the therapeutic effects of acetylsalicylic acid?

Answer 6

Anti-inflammatory, analgesic, antipyretic, and anti-clotting (TxA2 inhibition in platelet aggregation)

Question 7

What are the adverse effects of aspirin (and most NSAIDs)?

Answer 7

GI irritiation (PGE2 and PGI2 inhibition), Nephrotoxicity (too much use, or older patients), Bleeding/anemia (overuse with systemic or GI bleeding), Hypersensitivity reaction (0.2%), Salicylate toxicity (overdose, repiratory alkylosis, metabolic acidosis, coma, and death)

Question 8

What is the MOA of diflunisal?

Answer 8

Competitive inhibition of COX1 and COX2

Question 9

How do tolerability and half life of difluisal and aspirin compare?

Answer 9

Diflunisal is better at both; 3x potency in muscle

Question 10

What is the MOA of acetaminophen on COX?

Answer 10

Competitive inhibition of COX1 and COX2 EXCEPT in presence of peroxides or within the CNS

Question 11

How is acetominophen metabolized?

Answer 11

Phase 1 to excrete through the kidney; hepatotoxic by Phase 2 reaction in overdose that depletes glutathione

Question 12

What is the antiinflammatory action of acetominophen? Why?

Answer 12

None - not yet known

Question 13

When is acetominophen specifically used?

Answer 13

When a patient is intolerant to aspirin

Question 14

What are the indole compounds? What class are they in?

Answer 14

Sulindac and Indomethacin; NSAIDs

Question 15

What was the first use of indomethacin?

Answer 15

Gout

Question 16

How do indole compounds compare to aspirin in potency and side effects?

Answer 16

10x the potency, but more and more serious side effects in chronic use

Question 17

What is the most common NSAID?

Answer 17

Ibuprofen

Question 18

What are the propionic acid derivatives? What class of drug are they in?

Answer 18

Ibuprofen, naproxen, fenoprofen, ketoprofen, oxaprozin, and flurbiprofen; NSAIDs

Question 19

How do effectiveness and tolerability of Propionic acid derivatives compare to aspirin?

Answer 19

Both are better

Question 20

What is the general 1/2 life of propionic acid derivatives? What two differ?

Answer 20

Generally 1-2 hours, Naproxen=13hrs and Oxiprozin=50hrs

Question 21

What is the major enolic acid compound? What makes it good for MSK disorders?

Answer 21

Piroxicam for RA or OA or other inflammatory disorders; long (45hr) half life

Question 22

What is the use of ketorolac? What class is it in?

Answer 22

IM injection in post-op or topical for the eye; NSAID Heteroaryl Acetic Acid

Question 23

What are the coxibs?

Answer 23

COX2 inhibitors: Celecoxib and Etoricoxib

Question 24

How do the coxibs compare to general COX1/2 inhibitors in terms of efficacy and safety?

Answer 24

The lack of COX1 activity means no cardioprotective effects; some have high risk of MI and stroke and have been withdrawn; fewer GI side effects; Effecacy for anti-inflammatory, antipyretic and analgesic properties are similar to other NSAIDs

Question 25

What is the structural difference between coxibs and other NSAIDs?

Answer 25

Coxibs are larger to sterically hinder them from acting on the smaller COX1 active site

Question 26

What pathways (broader than COX1vsCOX2) are affected bt NSAIDs?

Answer 26

Prostaglandin, prostacyclin, and thromboxane synthesis; not leukotriene synthesis

Question 27

What is the only irrevesible NSAID?

Answer 27

Aspirin

Question 28

What are the three phases of inflammation?

Answer 28

Acute transient (local vasodilation/permeability), delayed subacute (infiltration by leukocytes), and chronic proliferative (tissue degeneration and necrosis)

Question 29

What is the effect of histamine?

Answer 29

local capillary dilation, edema due to permeability, and itching due to primary sensory neuron sensitization

Question 30

What are the effects of kinins?

Answer 30

pain from acute primary sensory neuron excitation and chronic arachidonic acid relase with pcv dilation

Question 31

When are COX1 and COX2 induced/active?

Answer 31

COX1 is constitutive in gastric/platelet/renal blood flow/parturition initiation and COX2 is inflammatory

Question 32

Match the prostaglandin/thromboxane with the cell source and major action: PGE2

Answer 32

Macrophages; protection of gastric mucosa, vasodilation, hyperalgesia

Question 33

What are eicosanoids?

Answer 33

arachidonic acid metabolites

Question 34

What is the source of arachidonic acid in inflammation? How is this relevant to injury response?

Answer 34

Arachidonic acid is derived from cell membrane phospholipids either during the injury (chemical/physical) process or within the kinin-mediated extracellular milieu

Question 35

What is the product of lipoxygenase metabolism of arachidonic acid?

Answer 35

leukotrienes

Question 36

What are the products of cyclooxygenase metabolism of arachidonic acid?

Answer 36

prostaglandins, prostacyclins, and thromboxanes

Question 37

Match the prostaglandin/thromboxane with the cell source and major action: PGD2

Answer 37

Mast cells; vasodilation and inhibition of platelet activation

Question 38

Match the prostaglandin/thromboxane with the cell source and major action: PGF2a

Answer 38

Mast cells; bronchoconstriction

Question 39

Match the prostaglandin/thromboxane with the cell source and major action: PGI2 (prostacyclin)

Answer 39

Endothelial cells; vasodilation and inhibition of platelet activation

Question 40

Match the prostaglandin/thromboxane with the cell source and major action: TxA2 (thromboxane)

Answer 40

Platelets; vasoconstriction, bronchoconstriction, and platelet aggregation