NSAIDS

Question 1

COX2 role:

Answer 1

Its production is increased when you are injured (involved in pathology of pain and anti-inflammation.)

Question 2

COX1 role:

Answer 2

regular housekeeping function (ex. protecting the gastric mucosa from HCL, platelet aggregation in blood clotting)

Question 3

Cyclooxygenase is:

Answer 3

an enzyme, dimer with 2 active sites.

Question 4

When Arachnoid Acid reaches the active site of Cyclooxygenase:

Answer 4

AA is transformed into a prostaglandin.

Question 5

NSAIDs drugs role:

Answer 5

Blocking the cyclooxygenase (COX) enzyme (so block the formation of prostaglandins)

Question 6

Injured cells release mediators:

Answer 6

Bradykinin (stimulator of pain)
Prostaglandins (PGE2 mostly)
Histamine
5HT

Question 7

How do we raise the set point or our internal thermostat and therefore, increasing body temperature leading to Fever?

Answer 7

PGE2 is produce in the hypothalamus and synthesize in the brain, which involves COX-2.

Question 8

How is the chronic use of NSAIDS can attack the epithelial cells lining the stomach and cause ulcer/gastritis?

Answer 8

Prostaglandins stimulate the production of the mucosal lining in the stomach (the mucus layer protects the gastric lining). NSAIDS use decreases the prostaglandins –> decrease mucus layer.

Question 9

Aspirin role:

Answer 9

Preventing the AA from being converted to PGH2 within the COX enzyme. Act on both COX1 and COX2

Question 10

Aspirin difference from others NSAIDS:

Answer 10

ASPIRIN bing IRREVERSIBLY and permanently inactivating/inhibiting COX, not the others NSAIDs.

Question 11

Prostaglandins (PGH2), the parent prostaglandins, can be transformed into:

Answer 11

TxA2 (Thromboxane A2): Platelets aggregation

PGE2: Inflammation, pain and gastro-protection

Question 12

Why is the Aspirin is the only NSAIDs working as anticoagulant?

Answer 12

Bc Platelet do not have nuclei, so when Aspirin bind irreversibly and permanently inactivate COX, it block for the life of the platelet (1 week)

Question 13

Salicylic acid is a (weak acid or base)?

Answer 13

Weak acid ( unionized form –> lipid-soluble) so when there is OD, we need to give Bicarbonate to change the PH environment of the urine into Basic environment to increase ionized form –> water-soluble!

Question 14

Aspirin toxicity is referred to:

Answer 14

Saicylism

Question 15

Aspirine in children can cause:

Answer 15

Reye syndrome (occur only with infection by certain virus)

Question 16

Traditional NSAIDs example:

Answer 16

Ibuprofen, naproxen..

Question 17

Traditional NSAIDs role:

Answer 17

Preventing the AA from being converted to PGH2 within the COX enzyme. Block REVERSIBLY both COX1 and COX2.

Question 18

COX2 Inhibitors example:

Answer 18

Celecoxib

Question 19

COX2 inhibitors role:

Answer 19

Act just on COX2 as the channel through which the drug enters to get into the enzyme is wider(bigger) than for COX1

Question 20

Acetaminophen act on:

Answer 20

COX3 and COX 4 (give relief of pain and fever but NOT peripheral relieve inflammation)

Question 21

N-acetylbenzoquinoamine is

Answer 21

Toxic compound a metabolite of Acetaminophen metabolized by P450 by transferase

Question 22

N-acetylbenzoquinoamine become inactivated by:

Answer 22

Glutathione

Question 23

Alcohol and Acetaminophen interaction cause:

Answer 23

More risk to OD bc of the toxic metabolites. Alcohol synthesize greater amounts of the toxic P450 metabolite and deplete the store of glutathione (not enough to inactivated all the N-acetylbenzoquinoamine)

Question 24

N acetylcysteine is:

Answer 24

a glutathione precursor (antidote of acetaminophen OD)