Arachidonic Acid

Question 1

What cleaves arachidonic acid off phospholipids in the membrane?

Answer 1

PLA2

Or PLC with DAG afterwards

Question 2

What are the 4 general things arachidonic acid can be turned into?

Answer 2

1. prostaglandins
2. thromboxanes
3. prostacyclin
4. Leukotrienes

Question 3

What will convert AA into prostaglandings?

Answer 3

cyclooxygenase enzymes

COX1 and COX2

Question 4

What do prostacyclins do in related to MIs?

Answer 4

They prevent MIs by blocking platelet aggregation

but also enhance bleeding, so…keep the balance

Question 5

If prostacyclin decreases MI risk, which AA-derived molecule will increase MI risk?

Answer 5

Thromboxanes - they promote vasoconstruction and clotting

Question 6

What cells make thromboxane?

Answer 6

platelets

Question 7

Which AA-derived molecule is most directly associated with inflammation - fever, pain, redness, swelling?

Answer 7

PGE2

Question 8

Which NSAID irreversibly blocks COX1 and COX2?

Answer 8

Aspirin

Question 9

Which NSAID only blocks COX2 and thus has a reduced risk of causing ulcers?

It’s the only one left on the market…

Answer 9

Celecoxib

(Celebrex)

Question 10

Which NSAID is the typical non-selective COX inhibitor used most often?

Answer 10

Ibuprofen

(Motrin)

Question 11

What is the disacvantage with the COX2 inhibitors?

Answer 11

They suppress prostacyclin synthesis as well, which promotes clotting in the coronary and cerebral circulation

Question 12

What were the two main COX2 inhibitors that were removed from the market?

Answer 12

Rofecoxib (Vioxx)

Valdecoxib (Bextra)

Question 13

Where does Acetaminophen (Tylenol) block COX in the body? What does this mean for its effects?

Answer 13

It only blocks COX in the CNS - NOT in the periphery

This means it’s anti-pyretic and analgesic, but NOT anti-inflammatory

Question 14

Why are only small doses of aspirin required?

Answer 14

It is an irreverislbe inhibitor of COX because platelets don’t have nuclei, so they can’t produce more.

Question 15

True or false: NSAIDs help deal with the symptoms of RA and can sometimes halt the progress fo the disease?

Answer 15

False - cannot half or reverse disease progression

Question 16

How do glucocorticoids act on the arachidonic acid pathway?

Answer 16

They are transcriptional regulators that reduced inflammation in general by reducing the number of lymphocytes, eosinophils, monocytes and basophils

In terms of the AA pathway, they inhibit PLA2, so you don’t get the release of AA from the membrane

Also block release of IL1, IL6, and TNF

Question 17

What blood cell count do glucocorticoids NOT reduce?

Answer 17

they increase the number of PMN leukocytes (Neutrophils)

Question 18

What are 4 examples of corticosteroids?

Answer 18

Dexamethasone (Decadron)

Hydrocortisone

Methylprednisolone (Medrol)

Prednisone (deltasone)

Question 19

What limits steroid use?

Answer 19

Toxicity….

osteoporosis

immune suppression

peptic ulcers (bc they block AA release)

myopathy

cataracts

fluid accumulation

hyperglycemia

Question 20

Will steroids stop RA progression?

Answer 20

No

Question 21

Which will block both prostaglandins and leukotriene symthesis: NSAIDS or steroids?

Answer 21

steroids (block at a step further up than COX)

Question 22

What will fish oil make in the body, and why does it reduce inflammation and MI risk?

Answer 22

It will make thomboxane A3 and Prostaglanding E3

Neither of these are effective

So bleeding tendency is increased, along with a virtual resistance to cardiovascular disease