PHARM - Anti-Inflammatory Drugs II: The Arachidonic Acid Pathway and NSAIDS - Week 6

Question 1

Name 5 things that inflammation can occur in response to.

Answer 1

Infection
Trauma
Chemicals
Heat
'Danger'

Question 2

What three protective mechanisms does inflammation convey?

Answer 2

Prevents infection
Clears damaged cells/debris
Facilitates healing

Question 3

List the two main anti-inflammatory actions of NSAIDs.

Answer 3

Inhibition of vascular dilation

Inhibits synergism with other mediators that enhance leakiness

Question 4

What three conditions can NSAIDs be used as an analgaesic?

Answer 4

Headache
Menstrual pain
Musculoskeletal pain

Question 5

What is often the preferred NSAID for use as an anti-pyretic agent?

Answer 5

Paracetamol

Question 6

List the three major chemical classes of NSAIDs.

Answer 6

Salicylates
Propionic acids
Acetic acids

Question 7

What chemical class of NSAIDs does aspirin fall under?

Answer 7

Salicylates

Question 8

What chemical class of NSAIDs does ibuprofen fall under?

Answer 8

Propionic acids

Question 9

What is the mechanism of action of salicylates?

Answer 9

Irreversibly acetylates COX

Question 10

What are the three main/common uses for aspirin?

Answer 10

Analgaesic
Antipyretic
Anti-thrombotic

Question 11

Name three possible side effects of aspirin.

Answer 11

Reyes syndrome
Tinnitus
Uric acid retention

Question 12

What is the mechanism of action of acetic acids?

Answer 12

Potent inhibitors of COX

Question 13

Which chemical class of NSAIDs is used largely for long-term treatment of inflammatory conditions (like rheumatoid arthritis)?

Answer 13

Acetic acids

Question 14

What is the major adverse effect of NSAIDs and when is it most common?

Answer 14

Inhibiting the normal regulatory role of prostanoids, most common when taken at high doses for long periods.

Question 15

List three adverse effects of inhibiting prostanoids.

Answer 15

Increased chance of GI ulceration/bleeding
Increased bleeding time
Renal impairment

Question 16

Is it more ideal to inhibit COX1 or COX2? Explain why.

Answer 16

COX2 because it results in decreased inflammation, while inhibition of COX1 can result in GI disturbances.

Question 17

Define coxibs, what they inhibit, and what symptom it is less likely to induce.

Answer 17

Inhibits both COX1 and COX2, but inhibits COX2 far more.

It results in less gastrointestinal adverse effects.

Question 18

Explain why some coxibs increase the risk of cardiovascular deaths and in which patient population COX2 inhibitors should be avoided.

Answer 18

COX2 is present in endothelial cells and not platelets, shifting hemostatic balance to pro-coagulation. Platelets have COX1 btw.
COX2 inhibitors should be avoided when patients have, or are at risk of having, cardiovascular disease.

Question 19

Is paracetamol an NSAID?

Answer 19

It is a poor inhibitor of COx and is not anti-inflammatory, and is generally not considered to be an NSAID

Question 20

What occurs with a paracetamol overdose?

Answer 20

Liver toxicity

Question 21

What are the two major effects of glucocorticoids?

Answer 21

Anti-inflammatory

Immunosuppressant

Question 22

What is the mechanism of action for glucocorticoids?

Answer 22

Binds to receptors inside the cell to modify gene transcription.

Question 23

Do glucocorticoids affect upregulation or downregulation of genes?

Answer 23

Both

Question 24

Name three kinds of anti-rheumatoid drugs.

Answer 24

NSAIDs
Glucocorticoids
Disease modifying anti-rheumatic drugs (DMARDs)

Question 25

What class of anti-rheumatoid drug does methotrexate fall under and what is its mechanism of action?

Answer 25

Is a non-biological DMARD

Acts as a folate antagonist, inhibiting DNA synthesis

Question 26

How can biological DMARDs be made?

Answer 26

Monoclonal antibodies

Question 27

Briefly describe in 3 steps the process of making monoclonal antibodies.

Answer 27

An antigen with multiple is introduced to an immune system (ie mouse) and allowed to form B-cells capable of producing antibodies against it.
This B-cell is merged with an immortal myeloma, forming a hybridoma. It is capable of indefinitely providing monoclonal antibodies.

Question 28

Consider monoclonal antibodies taken developed from a non-human line. Describe briefly in 2 steps how it can be humanised.

Answer 28

The DNA encoding the V-regions of the antibody can be isolated and cloned.
They are then spliced into human antibody cDNA, and expressed in a new cell line.

Question 29

How do janus ( ͡° ͜ʖ ͡°) kinase inhibitors work (mechanism of action). What are drugs of this class referred to as?

Answer 29

Targets multiple cytokines at the cell signalling level. They are called jakinibs.

Question 30

How do NSAIDs act as analgaesics?

Answer 30

They target synergistic prostaglandins like PGE2, minimising their hyperalgaesic effect.