Anti-inflammatory drugs

Question 1

Name 2 inflammatory mediators

Answer 1

Prostoglandins and thromboxanes

Question 2

What does NSAID mean?

Answer 2

Non steroidal anti inflammatory drug

Question 3

Whats the chemical name for aspirin?

Answer 3

Acetylsalicylic acid

Question 4

Name three NSAIDs

Answer 4

Aspirin, Paracetamol, Ibuprofen

Question 5

Generally what do NSAIDs do?

Answer 5

Inhibit production of inflammatory mediators
Prostaglandin and thromboxane

Question 6

What is a COX enzyme and why is it important for NSAIDs?

Answer 6

Cyclo- oxygenase
Target of NSAID is COX enzymes to inhibit production of inflammatory mediators

Question 7

What is an important property of prostaglandin and thromboxanes in immune response?

Answer 7

They are chemoattractants for immune cells
When there is inflammation immune cells will rapidly flow to it

Question 8

Which reaction does NSAID stop by inhibiting COX enzymes

Answer 8

Arachidonate -> (cox enxymes) -> Cyclic endoperoxides
Cyclic endoperoxides are converted into prostagladins and thromboxanes

Question 9

What are NSAIDs ineffective against and why?

Answer 9

Ineffective against mediators associated with tissue damage from chronic inflammatory conditions (rheumatoid arthritis)

Question 10

Why can NSAIDs be considered analgesic?

Answer 10

They reduce production of prostaglandins in inflamed tissues
Prostaglandins sensitise nociceptors (pain receptors) to inflam. meds.

Question 11

What is the property of anti-inflammatorys that lowers temperature?

Answer 11

Anti-pyretic
Interleukin-1 induces the expression of Cox2 which stimulates the hypothalamic production of prostaglandin E2 (PGE) which bind to receptors that work to increase temperature

Question 12

How many Cox enzymes are there?

Answer 12

3

Question 13

Which cox enzyme is inducible and how?

Answer 13

Cox 2
Induced by cytokines, growth factors or tumour promoters
Induced when responding to immune compromise

Question 14

Where in the cell are the cox enzymes found and how many subunits do they have?

Answer 14

Embedded in the ER membrane
Two identical subunits with two active sites
Peroxisome site and cox site

Question 15

What is the structural difference between cox 1 and cox 2 and why?

Answer 15

Cox 2 has a smaller channel than cox 1
Cox 2 has an isoleucine residue and cox 1 has a valine
Valine is much smaller than isoleucine therefore cox 1 channel = larger

Question 16

Why is the difference between cox 1 and 2 helpful?

Answer 16

Larger drugs can be used to selectively target cox 1 and not cox 2 due the difference in pore size

Question 17

Why can aspirin disrupt the mucus lining and what does this lead to ?

Answer 17

Prostaglandins secreted by cox 1 are important for maintaining mucus layer in the GI tract
Aspirin will inhibit cox 1 and prostaglandin production will stop
Mucus production will then halt, exposing the epithelial cells lining the tract
May cause ulcers

Question 18

Why can using an NSAID cause increased bleeding?

Answer 18

Cox 1 important for platelet expression
When inhibited less platelets expressed
Increased bleeding - more with GI ulcers

Question 19

How does aspirin work?

Answer 19

Suicide drug
Permenantly covalent bond between aspirin and Ser residue on cox enzyme
Prevents arachidonic acid from reaching the cyclooxygenase site
Prevents conversion to inflammatory mediator

Question 20

Why does it take roughly 4 hours for aspirin to wear off?

Answer 20

Takes 4 hours to make a new enzyme (suicide drug)

Question 21

Pros and cons of using cox 1 selective NSAID

Answer 21

pros - For stroke patients (anti-thrombolic)
Prevents blood clot formation
Cons- For blood thinning disorders can be dangerous
Gastrotoxicity

Question 22

Pros and cons of using cox 2 selective NSAID

Answer 22

Pros- anti inflammatory, analgesia
Cons- Some can increase risk of cardiovascular diseases
increases blood pressure and salt retention -> heart attack