Unit 2. Inflammation

Question 1

Acetylsalicylic acid (ASA)

Answer 1

Class: NSAID, salicylate
MOA: irreversibly acetylates COX1, 2; metabolite (salicylic acid) reversibly inhibits COX1, 2
Uses: antiplatelet, analgesic, antipyretic, anti-inflamm (in order of incr dose); can be taken as baby aspirin for MI, CVA prevention
Tox: GI irritation, bleeding+anemia, hepatotox, salicylate tox (O/D), nephrotox in elderly and hypovolemic
Note: not effective for visceral pain

Question 2

Diflusinal

Answer 2

Class: NSAID, salicylate
MOA: derivative of ASA, reversibly inhibits COX1,2
Uses: OA, MSK strains, sprains, pain after dental extraction, post-episiotomy pain
Tox: fewer GI than ASA, less effects on platelets

Question 3

Acetaminophen

Answer 3

Class: NSAID, para-amino phenol
MOA: revirsibly inhibits COX1, 2 (favors 1)
Uses: analgesic + antipyretic effects similar to ASA, but only weakly anti-inflammatory
Tox: renal tubular necrosis (w chronic abuse), hepatic necrosis w o/d, GI irritation (less than ASA)
Note: poor fxn in presence of peroxides (e.g. at sites of inflam); main metab via conjugation, but minor pathway via p450–> toxic intermediate (N-acetyl-benzoquineimine)–>usually conjugated w glutathione
*treat o/d w acetylcysteine (mucomyst), which replenishes glutathione levels

Question 4

Indomethacin

Answer 4

Class: NSAID, indole
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: RA (10x as potent as ASA), ankyl spond, OA, acute gout, closure of patent DA
Tox: at times–> TCpenia, aplastic anemia, severe frontal headaches; nephrotox in elderly, hypovol; do not give to children (besides for PDA)

Question 5

Sulindac

Answer 5

Class: NSAID, indole
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: RA, ankyl spond, OA, acute gout
Tox: (1/2 as potent as indomethacin, so less tox) at times–> TCpenia, aplastic anemia, severe frontal headaches; nephrotox in elderly, hypovol

Question 6

Ibuprofen

Answer 6

Class: NSAID, proprionic acid derivative
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: rheum disorders, OA, ank spond, postpartum pain, dysmenorrheal pain, many types of surgery
Tox: GI irritation, hepatotox (less freq than ASA); better tolerated than ASA, indoles
Note: half life of 1-2 hrs

Question 7

Flurbiprofen

Answer 7

Class: NSAID, proprionic acid derivative
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: rheum disorders, OA, ank spond, postpartum pain, dysmenorrheal pain, many types of surgery
Tox: GI irritation, hepatotox (less freq than ASA); better tolerated than ASA, indoles
Note: half life of 1-2 hrs; attains high synovial conc, available as topical opthalmic formulation

Question 8

Naproxen

Answer 8

Class: NSAID, proprionic acid derivative
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: rheum disorders, OA, ank spond, postpartum pain, dysmenorrheal pain, many types of surgery
Tox: GI irritation, hepatotox (less freq than ASA); better tolerated than ASA, indoles
Note: longer half life of 13 hrs (BID tx for arthritis)

Question 9

Oxaprozin

Answer 9

Class: NSAID, proprionic acid derivative
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: rheum disorders, OA, ank spond, postpartum pain, dysmenorrheal pain, many types of surgery
Tox: GI irritation, hepatotox (less freq than ASA); better tolerated than ASA, indoles
Note: much longer half life of 50 hrs (QD dosing)

Question 10

Piroxicam

Answer 10

Class: NSAID, Enolic acid
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: long-term Tx of RA or OA; also used in ankyl spond, acute MSK disorders, acute gout
Tox: NSAID typical (GI, nephro, hepato), but less than ASA
Note: very long t1/2 of 45 hrs–> QD dosing

Question 11

Ketoralac

Answer 11

Class: NSAID, Heteroaryle acetic acid
MOA: reversibly inhibits COX1, 2 (favors 1)
Uses: post-op pain (opioid-like analgesic efficacy), inflamm eye conditions
Tox: relatively non-irritating; some NSAID typicals
Note: injectable (IM) t1/2 of 4-6 hrs; topically on eye; one of the few parenteral NSAIDS

Question 12

Celecoxib

Answer 12

Class: Cox-2 inhibitor; “coxibs”
MOA: selectively inhibits COX-2 (too bulky to interact w COX-1 site)
Uses: same anti-inflamm, antipyretic, analgesic effects as NSAIDS (but no impact of platelets, so no cardioprotective effects)
Note: contra-indicated in pts w heart problems and in pregnant women

Question 13

Etoricoxib

Answer 13

Class: Cox-2 inhibitor; “coxibs”
MOA: selectively inhibits COX-2 (too bulky to interact w COX-1 site)
Uses: same anti-inflamm, antipyretic, analgesic effects as NSAIDS (but no impact of platelets, so no cardioprotective effects)
Note: contra-indicated in pts w heart problems and in pregnant women

Question 14

7 classes of NSAIDS

Answer 14

1. Salicylates
2. Para-amino phenols
3. Indoles
4. Propionic acid derivatives
5. Enolic acids
6. Heteroaryl acetic acids
7. COX-2 selective inhibitors (“coxibs”)

Question 15

Name the salicylate NSAIDS

Answer 15

Acetylsalicylic acid (ASA), Diflusinal

Question 16

Name the para-amino phenol NSAID

Answer 16

Acetaminophen

Question 17

Name the indole NSAIDS

Answer 17

Indomethacin, Sulindac

Question 18

Name the propionic acid deriv NSAIDS

Answer 18

Ibuprofen, Flurbiprofen, Naproxen, Oxaprozen

Question 19

Name the enolic acid NSAID

Answer 19

Piroxicam

Question 20

Name the heteroaryl acetic acid NSAID

Answer 20

Ketorolac

Question 21

Name the “coxibs”

Answer 21

Celecoxib , Etoricoxib (COX-2 inhibitors)