56: NSAIDs and Treatment of Gout

Question 1

4 classic inflammatory symptoms

Answer 1

redness/rubor
swelling/tumor
heat/calor
pain/dolor

Question 2

molecular inflamamtory mediators

Answer 2

bradykinin
substance 
histamine
5HT
arachidonic acid metabolites: prostaglandin, thromboxanes, prostacyclin
cytokine TNF-a

Question 3

functional characteristics of NSAIDs

Answer 3

analgesia
antipyretic
anti-inflammatory
target prostaglandin production

therefore… acetaminophen is not and NSAID because it is not anti-inflammatory

Question 4

convert arachindonic acid to prostaglandins

Answer 4

COX

Question 5

consituitve, protective COX

v.

inducible, inflammatory COX

Answer 5

COX-1

COX-2

Question 6

what can be used for antipyretic in children and viral diseases?

Answer 6

acetaminophen

aspirin and other PG synthesis inhibitors NOT recommended; can be used in adults

Question 7

MOA aspirin

Answer 7

irreversible COX inhibitor and therefore inhibitor of PG synthesis

significant portion hydrolyzed to salicylic acid (reversible COX inhibitor)

travels bound to plasma prtns

Question 8

low dose v. high dose aspirin

Answer 8

low dose: analgesic antipyretic

high dose: antiinflammatory

Question 9

how does aspirin produce an anti-pyretic effect?

Answer 9

blocks production of PG in CNS to reset temperature control at hypothalamus, facilitating heat dissipation by vasodilatation

Question 10

ASA ______- bleeding time

Answer 10

prolooongs

anti-thrombotic and anti-coagulant effects

Question 11

phophylactic uses of ASA

Answer 11

inhibit platelet hyperaggregaion

protective against CAD, MI, DVT post op

Question 12

adverse effects ASA

Answer 12

• GI tract upset due to COX1 inhibition **
• GI irritation due to inhibition of cytoprotective PG (PGE2 and PGI2 decrease acid secretion)
• platelet inhibition –> prolonged bleeding time
• hepatic and renal toxicity
• hypersensitivity (pruritus)
• tinnitus
• reye’s syndrome (encephalopathy)

Question 13

what kinds of hepatic and renal toxicity may occur with ASA?

Answer 13

aymptomatic hepatitis

decreased kidney function with chronic use

• decreased renal blood flow
• sodium retention/edema

Question 14

NSAID for gout and ankylosing sponylitis

Answer 14

indomethacin

Question 15

have analgesic, antipyretic, and anti-inflammatory effects but with less GI adverse effects

Answer 15

COX2 inhibitors

no impact on platelet aggregation (COX1) - incidence of thrombotic events associated with COX2 inhibitors

Question 16

celecoxib is FDA approved for ..

Answer 16

RA and osteoarthritis

black box warning- cardiovascular

Question 17

actions of acetaminophen

Answer 17

pain reliever and fever reducer (analgesic and anti-pyretic only) not anti-inflammatory

Question 18

acetaminophen might react with

Answer 18

ethanol, isoniazid etc

because metabolized by cP450

Question 19

therapeutic dose of acetaminophen

Answer 19

15mg tid

narrow therpeutic index, 150 - liver necrosis, 350 - liver failure

Question 20

how is capsaicin used to treat RA, osteoarthritis, and neuralgia?

Answer 20

topically

binds and activates vanilloid receptor –> release substance P
prolonged activation of these neurons depletes and prevent re-accumulation of substance P

Question 21

limitations for each NSAID

Answer 21

ketorlac- GI and renal adverse effects limit use
Indomethacin and tolmetin - greatest toxicity
Salicylate, ASA and ibuprofen - least toxic
Diclofenac and sulindac - increased liver function abnormalities
celecoxib - safest for pts with high risk GI, more risk CV toxicity and $

Question 22

metabolic disease characterize dby recurrent episodes of acute arthritis due to deposits of monosodium urate (uric acid crystals) in joints and cartilage

Answer 22

gou

usually associated with hyperuriciemia

Question 23

first line treatment gout

Answer 23

NSAIDs - indomethacin

can use other NSAID (not asa), corticosteroids or intra-articular steroid injection as well

Question 24

how does colchicine treat gout?

Answer 24

reduces pain and inflammation without altering metabolism or excretion of uric acid
(inhibits leukocyte migration and phagocytosis)

adverse effect = diarrhea

Question 25

xanthine oxidase inhibitors

Answer 25

allopurinol
febuxostat

reduce production of UA

Question 26

uricosuric drugs

Answer 26

probenecid
sulfinpyrazone

increase renal excretion of UA