NSAIDs & Immunosuppressants

Question 1

NSAIDs have eicosanoid-depressing action. what are eicosanoids?

Answer 1

PGs and interleukins

Question 2

what catalyzes the formation of PGs and thromboxane from arachidonic acid?

Answer 2

COX enzymes

Question 3

MOA of NSAIDs?

Answer 3

non-selective inhibitors of COX-1 and COX-2 enzymes

Question 4

all NSAIDs, except _____ irreversibly inhibit COX-1 and COX-2 by acetylation of the enzymatic active site

Answer 4

aspirin

Question 5

what is leukotrienes usually accompanied by?

Answer 5

release of histamine

Question 6

housekeeping enzyme that is found in the stomach

Answer 6

COX-1

Question 7

what hormone is a major product of COX-1? what does it do?

Answer 7

thromboxane
platelet aggregation

Question 8

why is aspirin effective at reducing cardiac events?

Answer 8

because it inhibits platelet COX-1

Question 9

enzyme that induces the inflammatory response

Answer 9

COX-2

Question 10

where does COX-2 work? (3)

Answer 10

kidney
lungs
inflammatory cells

Question 11

what 2 drug types inhibit COX-2 gene expression?

Answer 11

NSAIDs
glucocorticoids

Question 12

why can the use of NSAIDs not eliminate leukotriene synthesis?

Answer 12

NSAIDs do not inhibit lipoxygenases

Question 13

what is required for NSAIDs to be an antiinflammatory?

Answer 13

large doses 600-800mg

Question 14

how does pyresis occur?

Answer 14

pyrogens stimulate interleukin-1 release = stimulates PG in hypothalamus = increases thermo set point

Question 15

what is the DOC for pyresis? what should be avoided when taking it?

Answer 15

acetaminophen

avoid ethanol

Question 16

how does pain occur?

Answer 16

PGs sensitize pain fibers to stimuli

Question 17

what makes acetaminophen different?

Answer 17

only works in the CNS

Question 18

what NSAID is used to inhibit premature labor?

Answer 18

indomethacin

Question 19

what kind of inflammation can NSAIDs work well for? (3)

Answer 19

osteoarthritis
RA
ankylosing spondylitis

Question 20

how is aspirin converted to salicylate?

Answer 20

by first pass hepatic metabolism

Question 21

what does it mean when large doses of aspirin exhibit non-linear kinetics?

Answer 21

it has an increased half life

Question 22

what is a sign that aspirin dose is too high?

Answer 22

tinnitus

Question 23

what NSAID can interfere with the antiplatelet effect of aspirin by preventing acetylation of acetylsalicylic acid?

Answer 23

ibuprofen

Question 24

what kind of NSAIDs have little effect on platelets, thus little risk of bleeding?

Answer 24

nonacetylated salicylates

Question 25

what's important about nonsalicylate NSAIDs?

Answer 25

less GI toxicity

Question 26

what are the 4 nonsalicylate NSAIDs?

Answer 26

diclofenac etodolac ibuprofen indomethacin

Question 27

which 2 nonsalicylate NSAID are relatively COX-2 selective?

Answer 27

diclofenac etodolac

Question 28

which 2 nonsalicylate NSAIDs have some inhibitory action against lipoxygenase? (decrease leukotriene)

Answer 28

diclofenac indomethacin

Question 29

ADR of diclofenac?

Answer 29

increased risk of MI

Question 30

ADR of indomethacin? (2)

Answer 30

CNS (esp in elderly) increased risk of GI ulcers

Question 31

which nonsalicylate NSAID is only used for acute moderately severe pain?

Answer 31

indomethacin

Question 32

-coxib

Answer 32

COX-2 inhibitors

Question 33

what is the half life of celecoxib?

Answer 33

10 hours

Question 34

what is celecoxib used for? (3)

Answer 34

arthritis dysmenorrhea post-surgical pain

Question 35

ADR of celecoxib? (2)

Answer 35

increased risk of MI increased risk of stroke

Question 36

why do NSAIDs have a small Vd?

Answer 36

highly bound to plasma albumin

Question 37

how are NSAIDs mostly excreted?

Answer 37

kidneys

Question 38

what are 3 ADR specific for aspirin/salicylates? what causes them?

Answer 38

hypersensitivity - rhino conjunctivitis angioedema urticaria increased leukotriene synthesis

Question 39

a patient presents with rhino conjunctivitis, angioedema, and urticaria after taking aspirin/salicylate. about when did the patient take it?

Answer 39

within the last 3 hours

Question 40

why do NSAIDs cause increased BP?

Answer 40

allow full vasoconstriction caused by NE

Question 41

how do NSAIDs cause salt/water retention? what can it lead to? (3)

Answer 41

decrease renal blood flow and GFR hyperkalemia interstitial nephritis reversible acute kidney failure

Question 42

the nephrotoxicity of celecoxib is = to _____ NSAIDs

Answer 42

non-selective

Question 43

how do NSAIDs cause GI ulceration and bleeding?

Answer 43

inhibit PG who are produced by the stomach to maintain the mucosal integrity

Question 44

what can be given to geriatric patients with prior history of NSAID-induced GI ulceration?

Answer 44

misoprostol

Question 45

stable analogue of PGE1 used to treat gastric erosions and ulcerations caused by NSAIDs

Answer 45

misoprostol

Question 46

what 2 products can be used together to prevent NSAID-induce GI ulcers but can predispose patients to C. diff?

Answer 46

NSAID + H2 receptor antagonist (famotidine) OR NSAID + proton pump inhibitor (omeprazole)

Question 47

what do many physicians Rx to treat arthritis in elderly patients?

Answer 47

NSAID + PPI (omeprazole)

Question 48

what CNS reactions can NSAIDs cause?

Answer 48

headache rebound headache dizziness

Question 49

why are NSAIDs CI in pregnancy?

Answer 49

can cause fatal pulmonary hypertension in fetus

Question 50

what is safe to use in pregnancy to treat pain?

Answer 50

acetaminophen

Question 51

ADR of acetaminophen?

Answer 51

hepatotoxicity

Question 52

when does toxicity from acetaminophen occur?

Answer 52

when glutathione is depleted *(glutathione pushes the toxic metabolite out of the system)*

Question 53

what is the treatment for acetaminophen overdose?

Answer 53

gastric lavage + IV N-acetylcysteine

Question 54

how does ethanol increase the risk of acetaminophen hepatic toxicity?

Answer 54

ethanol increases CYP450

Question 55

class of drugs that increase gene expression of lipocortin which inhibits phospholipase A2 and inhibits inflammation

Answer 55

corticosteroids prednisone prednisolone

Question 56

drug class that suppresses interleukin-2 production in T lymphocytes

Answer 56

calcineurin inhibitors

Question 57

what are the 2 calcineurin inhibitors?

Answer 57

cyclosporine tacrolimus

Question 58

which calcineurin inhibitor is used to prevent graft-vs-host disease?

Answer 58

cyclosporine

Question 59

which calcineurin inhibitor is used to reduce risk of organ rejection?

Answer 59

tacrolimus

Question 60

ADR of cyclosporine?

Answer 60

swelling gums

Question 61

how are corticosteroids metabolized?

Answer 61

liver

Question 62

suppress intracellular signaling pathway important for cell growth and proliferation of T lymphocytes

Answer 62

mTOR inhibitors

Question 63

what are the 2 mTOR inhibitors?

Answer 63

Sirolimus Everolimus

Question 64

what is sirolimus used for?

Answer 64

reduce risk of organ rejection by coating coronary stents

Question 65

what is everolimus used for? (2)

Answer 65

reduce risk of organ rejection HER-2 negative breast cancer

Question 66

blocks DNA synthesis and expansion of lymphocyte populations

Answer 66

IMDH inhibitors

Question 67

what are the 3 IMDH inhibitors?

Answer 67

azathioprine mycophenolate leflunomide

Question 68

what are the 3 uses for azathioprine and mycophenolate?

Answer 68

RA Crohn's disease transplants

Question 69

what are the 2 uses for leflunomide?

Answer 69

RA HER-2 negative breast cancer

Question 70

which 2 immunosuppressants can be used for HER-2 negative breast cancer?

Answer 70

everolimus leflunomide