NSAIDs & DMARDs

Question 1

NSAIDs act through _

Answer 1

inhibition of prostoglandins

Question 2

cyclo-oxygenases (COX1/COX2)

Answer 2

synthesize prostoglandins and thromboxanes

Question 3

prostoglandin effects

Answer 3

pain by lowering threshold of pain receptors, fever, inflammation

Question 4

glucorticoids

Answer 4

induce lipocortin that inhibits PLA2 for broad anti-inflammatory response

Question 5

COX1

Answer 5

constitutive activation; production of platelet clotting factors, parturition, stomach mucosa, ion excretion

Question 6

COX2

Answer 6

activated by inflammatory stimulus and mostly transcribed in macrophages; causes inflammation, swelling, pain, redness

Question 7

COX1 for _

Answer 7

prevention of cardiovascular events

Question 8

COX2 for _

Answer 8

anti-inflammatory/analgesic reasons

Question 9

NSAIDs three therapeutic actions

Answer 9

fever, pain, inflammation

Question 10

acetaminophen lacks _

Answer 10

anti-inflammatory effects

Question 11

analgesic action of NSAIDs

Answer 11

PGE2 sensitizes nerve endings to action of bradykinin, histamine, and other chemical mediators released by inflammatory process –> by decreasing PGE2, pain is decreased

Question 12

ketorolac

Answer 12

can be used in severe pain for short duration

Question 13

dose-dependent effects of salicylates

Answer 13

lower dose has an analgesic effect while higher dose has an anti-inflammatory effect

Question 14

antipyretic (fever) action of NSAIDs

Answer 14

cytokines (mainly IL-1) stimulate hypothalamus to release PGE2 which leads to an increase in body temp –> decreasing PGE2 will inhibit this

Question 15

low dose aspirin

Answer 15

selectively inhibits COX1 which reduces the production of TXA2 to prevent vasoconstriction and platelet aggregation

Question 16

salicylic acid

Answer 16

topically to treat acne, corns, calluses, warts

Question 17

methyl salicylate

Answer 17

used externally as a cutaneous counterirritant

Question 18

diclofenac

Answer 18

topical treatment of osteoarthritis

Question 19

side effects associated with COX1 inhibition

Answer 19

peptic ulcers and GI bleeding

Question 20

side effects associated with COX inhibition

Answer 20

water retention, hypertension, kidney injury

Question 21

side effects associated with COX2 inhibition

Answer 21

stroke and myocardial infection

Question 22

gastrointestinal adverse effects

Answer 22

PGI2 inhibits gastric acid secretion and PGE2/PGF2 promote mucus synthesis so inhibition will cause bleeding and ulceration

Question 23

renal adverse effects

Answer 23

PGE2/PGI2 are responsible for maintaining renal blood flow so inhibition will cause retention of sodium and water

Question 24

cardiac adverse effects

Answer 24

agents with higher COX-2 selectivity can increase risk for platelet aggregation and vasoconstriction by inhibiting PGI2/TXA2

Question 25

naproxen

Answer 25

least harmful NSAIDs for patients with CV contraindications

Question 26

NSAIDs and asthma

Answer 26

inhibition of prostoglandin synthesis will shift the precursors to make leukotrienes which causes asthma, anaphylaxis, and smooth muscle contraction

Question 27

celecoxib

Answer 27

selective COX-2 inhibitor for the treatment of RA, osteoarthritis, and acute pain

Question 28

celecoxib metabolism

Answer 28

metabolized by CYP2C9

Question 29

fluconazole

Answer 29

inhibits CYP2CP, causing increased celecoxib levels

Question 30

N-acetylcysteine

Answer 30

antidote for acetaminophen OD

Question 31

DMARDs

Answer 31

disease modifying antirheumatic drugs; can suppress rheumatoid process and bring about a remission but do not have nonspecific anti-inflammatory or analgesic action

Question 32

traditional DMARDs

Answer 32

non-biologic; typical one is methotrexate

Question 33

biologic DMARDs

Answer 33

non-TNF inhibitors; monoclonal Abs; used when inadequate response with traditional DMARDs

Question 34

methotrexate

Answer 34

folic acid antagonist that inhibits cytokine production and purine NT synthesis leading to immunosuppressive and anti-inflammatory effects; for RA

Question 35

hydroxychloroquine

Answer 35

used for early, mild RA and can be combined with methotrexate

Question 36

hydroxychloroquine side effects

Answer 36

ocular toxicity

Question 37

methotrexate side effects

Answer 37

hepatic and GI; contraindicated in pregnancy

Question 38

DMARDs begin to show a response within _

Answer 38

weeks to months

Question 39

leflunomide

Answer 39

inhibits DHODH to cause cell arrest of autoimmune lymphocytes; used in patients with CI for methotrexate

Question 40

leflunomide side effects

Answer 40

flu-like symptoms, alopecia, rash; contraindicated in pregnancy

Question 41

sulfasalazine

Answer 41

similar to leflunomide

Question 42

TNF-alpha inhibitors

Answer 42

biologic DMARDs; response within 2 weeks but only used after inadequate response to traditional DMARDs

Question 43

TNF-alpha inhibitor effects

Answer 43

heart failure, increased risk of cancer

Question 44

non-TNF biologics

Answer 44

also used after inadequate response but CAN NOT be used with TNF-alpha inhibitors

Question 45

tofacitinib

Answer 45

inhibitor of janus kinase and can be used for RA if no response to methotrexate