Inflammation

Question 1

Which class do acetlysalicylic acid and Diflunisal belong to?

Answer 1

salicylates

Question 2

What is the mechanism of action of Diflunisal?

Answer 2

reversibly inhibits COX1 and 2

longer half life than aspirin, less GI side effects, less Platelet effects.

Has Analgesic effects and wheal antipyretic activity.

Question 3

COX 1 vs COX 2

Answer 3

Cox 1 : Constitutively produced
Gastric protection, platelet aggregation, renal blood flow autoreg, initiation of parturition (PGF2)

Cox 2 : Induced during Inflammation –> produces prostaglandins at the site of inflammation/ tissue injury

Both are inhibited by NSAIDS

Question 4

What is the mechanism of action of acetylsalicylic acid and its metabolite salicylic acid?

Answer 4

Irreversibly acetylates COX-1 and -2;

metabolite, salicylic acid reversibly inhibits COX-1 and -2

Question 5

What is acetylsalicylic acid used to treat?

Answer 5

Antiplatelet, analgesic and antipyretic, and anti-inflammatory (in ascending order of amount taken)

Question 6

What is Diflunisal used to treat?

Answer 6

Osteoarthritis, cancer pain from Bone mets, musculoskeletal strains/sprains, pain after dental extraction, and postepisiotomy pain

Question 7

What is acetaminophen used to treat?

Answer 7

analgesic and antipyretic (minimal anti-inflammatory b/c of its poor ability to inhibit COX in the presence of a high conc. of peroxides, which are usually found at the site of inflammation. Also, COX inhibition may be disproportionately pronounced in the brain –> hence the antipyretic efficacy)
usually used in patient intolerant to aspirin

Question 8

What can happen when acetaminophen is chronically abused or overdosed?

Answer 8

@ an ordinary dose: virtually no side effects

chronic abuse- renal tubular necrosis
overdose-hepatic necrosis from depletion of glutathione

Question 9

Which has more GI side effects; acetlysalicylic acid or Diflunisal?

Answer 9

acetylsalicylic acid

Question 10

Name the 2 Indoles that reversibly inhibit COX1 and 2 (with a preference for COX1)

Answer 10

Indomethacin and Sulindac (half as potent as indomethacin)

Question 11

Name the para-amino phenol that reversibly inhibits COX1 and 2.

Answer 11

Acetaminophen

Question 12

Name the 4 proprionic acid drugs that reversibly inhibit COX 1 and 2 (with a preference for COX1).

Answer 12

Ibuprofen,
Naproxen (Aleve: 13 hr half life),
Flurbiprofen (obtains high synovial conc, available for topical opthalmic formulation)
Oxaprozin (Daypro: 50 hr half life)

Question 13

What medication can be used to treat acetaminophen overdose?

Answer 13

acetylcysteine (MUCOMYST) to protect the liver

Question 14

What are the indoles Indomethacin and Sulindac used to treat and what are their side effects?

Answer 14

Rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout
side effects- thrombocytopenia, aplastic anemia, and severe frontal headaches and nephrotoxicity in elderly/hypovolemic

Question 15

What are the proprionic acid drugs used to treat? (Ibuprofen, Naproxen Flurbiprofen, and Oxaprozin)

Answer 15

Rheumatic disorders, osteoarthritis, ankylosing spondylitis, postpartum pain, dysmenorrheal pain, and many types of surgeries

Question 16

What are the side effects of the proprionic acid drugs?

Ibuprofen, Naproxen Flurbiprofen, and Oxaprozin

Answer 16

GI irritation and hepatotoxicity (less frequent than aspirin)

Question 17

List the proprionic acid derivatives in order of increasing half life length.

Answer 17

Ibuprofen and Flubiprofen, Naproxen and Oxaprozin

Question 18

What class of drugs is Ketorolac from and what is its mechanism of action?

Good alternative to opiods: 4-6 hr half life

Answer 18

heteroaryl acetic acids; reversibly inhibits COX 1 and 2 (with a preference for COX1)

Question 19

What class of drugs is Piroxicam from and what is its mechanism of action?

Answer 19

Enolic acid; reversibly inhibits COX1 and 2. favors COX 1

Question 20

Name the 2 selective COX2 inhibitors.
“COXIBS”
Larger molecules than NSAIDS and fit the larger hydrophobic channel of COX2 better.

Answer 20

Celecoxib (x10-20 more COX2 selective) and etoricoxib (x100 more selective for COX2)

Have no effects on platelets therefore aren’t cardio protective like the traditional NSAIDS.

Question 21

What is piroxicam used to treat and how often is it taken?

Answer 21

Long-term treatment of rheumatoid arthritis or osteoarthritis, also ankylosing spondylitis, acute musculoskeletal disorders, acute gout; taken once per day because long half life (45hrs)

Question 22

What is ketorolac used to treat and how is it administered?

Answer 22

Post-operative pain; IM injection
inflammatory eye conditions; topically

Fairly, nonirritating to tissues

Question 23

What are the selective COX2 inhibitors used to treat?

Answer 23

Same anti-inflammatory, antipyretic, and analgesic effects as NSAIDs with less GI toxicity

Question 24

What limits the use of Indomethacin?

SHLDNT BE GIVEN TO KIDS!! EXCEPT- FOR CLOSURE OF THE DUCTUS ARTERIOSUS FOR WHICH IT IS FDA APPROVED!!

Answer 24

TOXICITY! Nephrotoxicity in the elderly and the hypovolemic

Otherwise, it is 10x more potent than aspirin

Question 25

In which patients are COX2 inhibitors contraindicated?

Answer 25

patients with heart problems/pregnancy

Question 26

What are some of the side effects of the salicylates?

Answer 26

GI Irritation, nephrotoxicity (more so in elderly or hypovolemic), bleeding and anemia, hepatotoxicity, hypersensitivity reaction and toxicity