NSAIDS and Related Drugs I

Question 1

All NSAIDS inhibit________that converts _____ to _____.

Answer 1

cyclo-oxygenase enzymes (COXs)

that convert arachidonic acid (AA) into prostaglandins (PGs)

Question 2

Prostaglandins mediate 3 main effects in the body?

Answer 2

inflammation, fever, and pain

Question 3

Most cells synthesize arachidonic acid (AA) and COX converts to PG. The notable exception are what cells involved in coagulation?

Answer 3

Platelets

Question 4

NSAIDS go by another name?

Answer 4

non-opioid analgesics

Question 5

anti-inflammatory STEROIDS act on _______ to inhibit the production of_______ and ______.

Answer 5

NUCLEAR TRANSCRIPTION FACOTRS to inhibit the production of PHOSPHOLIPASE A2 (prevents AA converstion) and COX.

Question 6

Glucocorticoids inhibits all metabolites of ______ and also decrease inflammation by what other effect?

Answer 6

AA (arachidonic acid)…….immune system suppression

Question 7

Side effects (4) of opioids that NSAIDS do not share

Answer 7

sedation, respiratory depression, tolerance, dependence

Question 8

COX enzymes convert AA to _______ and _______, the two precursors of all other of all other ________ and ________.

Answer 8

PG-G2 and PG-H2, the two precursors of all other PG’s and THROMBOXANES (TX).

Question 9

What is the rate limiting step in PG synthesis?

Answer 9

COX activity

Question 10

Most NSAIDs (aspirin, ibuprofen, naproxen) inhibit both \_\_\_\_\_\_\_, and \_\_\_\_\_\_\_\_, usually
with stronger inhibition of \_\_\_\_\_\_\_\_.

Answer 10

COX-1 and COX-2 with stronger inhibition of COX-1

Question 11

Pain can be treated by inhibiting:

Answer 11

COX-1 and COX-2

Question 12

Fever can be treated by inhibiting:

Answer 12

COX-1

Question 13

Inflammation can be treated by inhibiting

Answer 13

COX-2

Question 14

Which NSAID is more selective for COX-2

Answer 14

Celecoxib

Question 15

Which NSAID is 10x more selective for COX-1

Answer 15

Aspirin

Question 16

COX enzymes are also known as

Answer 16

PG-H synthases (PGHS’s)

Question 17

PGHS-1 converts AA to PG in platelets. This decreases/increases aggregation?

Answer 17

increases. Aspiring inhibits COX-1.

Question 18

Name two events leading to inducible cyclo-oxygenase conversion of AA to PG:

Answer 18

inflammation and tissue damage (wounds).

Question 19

Fever is modulated by which enzyme?

Answer 19

COX-1

Question 20

Which NSAIDS reduce clotting?

Answer 20

Just one: Aspirin

Question 21

ASA is cleaved into which two molecules

Answer 21

acetyl and salicylate

Question 22

Which ASA derivative is mostly responsible for the anti-inflammatory and analgesic effects?

Answer 22

Salicylate….the molecule shared with all the other salicylate NSAIDS

Question 23

COX can be inhibited by both the acetyl and salicylate groups of ASA. T/F

Answer 23

true

Question 24

What major difference distinguishes aspirin from all other NSAIDS?

Answer 24

It’s acetyl group which irreversibly binds to COX.

Question 25

Where do 80-90% of the first tab of aspirin derivatives bind?

Answer 25

albumin

Question 26

Name significant aspirin drug interactions

Answer 26

displaces warfarin, methotrexate, sulfonamides, others…

Question 27

Which cells in the body are thought to bind 99% of the acetyl group of ASA

Answer 27

vascular endothelial cells and platelets

Question 28

Which part of ASA is toxic

Answer 28

salicylates

Question 29

Explain first order metabolism of salicylates. Dose? Where does it occur? What are the products?

Answer 29

2-3 tabs/4 hours (2-10mg%). Liver. Saturable. -Glycine salts and Glucuronide salts

Question 30

Explain zero order metabolism of salicylates. When? Where? Dose? Products?

Answer 30

When first order metabolism becomes saturated at 4-5 tabs/4-6 hrs. Kidney. Excreted free salicylates.