NSAIDS

Question 1

Element of some NSAIDs such as ibuprofen and flurbiprofen in binding to the active site

Answer 1

ketone group or carboxylic acid ..maybe

Question 2

NSAIDS to known

Answer 2

Ibuprofen 
Flurbiprofen 
Ketoprofen
Indomethacin
Diclofenac
Celecoxib
Piroxicam

Question 3

Precursor of other NSAIDs

Answer 3

Aspirin

Question 4

Explain a little about NSAIDs

Answer 4

Injury leads to the activation of phospholipase which actually tackled the phospholipids in the cell membrane. In the cell membrane, there is arachidonic acid which is an omega 6 derivative and is the precursor of a lot of proinflammatory molecules. There are a lot of enzymes that use arachidonic acid as a substrate and produce lots of proinflammatory molecules.

There are two enzymes that process arachidonic acid
1. Lipooxygenase and 2. Cycloxygenase

When arachidonic acid is being processed by cyclooxyrgenase, it produces lots of proinflammatory molecules such as prostaglandins, thromboxane and prostacycline. Prostaglandins have proinflammatory effects, so if production is stopped then inflammation is decreased. The NSAIDs block cyclooxyrgenase which transforms arachidonic acid into proinflammatory molecules.

Question 5

3 isoenzymes of COX

Answer 5

COX-1 expressed in periphery and almost all tissues (stomach mucous lining) Increases secretion of gastric mucus and increases the secretion of bicarbonate in the stomach.

COX-2 (tissues )

COX-3 mostly expressed in the brain.

Prostaglandins can also increase uterine contractions.

Question 6

NSAIDS work by

Answer 6

inhibiting COX which transforms arachidonic acid into all these things, mostly prostaglandins. Some prostaglandins are involved in housekeeping functions so inhibiting these can also have adverse effects.

Question 7

Ways to to solve the problems with over inhibiting prostaglandins?

Answer 7

1. Give NSAID with “good prostaglandins”

2. COX-2 inhibitory

Question 8

The problem with a COX-2 inhibitor such as Celecoxib

Answer 8

effects the synthesis of prostacyclines (blood clotting0 and patients started to have heart attacks.

Question 9

Blocking COX involved in blocking thromboxane which

Answer 9

prevents blood clotting.

Question 10

Arachidonic acid can also be attacked by

Answer 10

Lipooxygenase which transforms arachidonic acid into Leukotrenes which are proinflammatory molecules that effect mostly upper respiratory tract and cause bronchoconstriction, so blocking Leukotrene synthesis is used in the treatment of Asthma.

Question 11

Side effect of NSAIDs in children (specially aspirin)

Answer 11

could induce asthma. Because it is blocking COX results in arachidonic acid being tackled by a lot of lipoxygenase which produces a lot of leukotrienes which cause bronchoconstriction “aspirin induced asthma”

Question 12

Why is aspirin dangerous

Answer 12

bonds covalently to active sites . must be replaced by synthesis of new enzymes ,, all other NSAIDs bind reversibly.

Question 13

Fate of arachdodonic acid

Answer 13

can be hit by COX (think prostaglandins) or can be hit by Lipooxygenase (think Leukotrienes)

Question 14

Enzymes that tackle Arachidonic acid

Answer 14

COX

Lipooxygenase

Question 15

Enzymes effected by NSAIDs

Answer 15

COX blocking

also over abundance of Leukotrienes due to high AA Processing by lipooxygenase

Question 16

Why can aspirin lead to asthma

Answer 16

blocks COX so AA process by lipoxygenase which leads to lots of leukotrienes that cause bronchoconstriction.

Question 17

Disease modifying anti rheumatic drugs (DMAD)

Answer 17

Cyclosporine
Methotrexate
Azathioprine

these target certain cells of the immune system

Also there is Biologic disease modifying anti rheumatic drugs :monoclonal antibodies

Question 18

DMADS have

Answer 18

increased side effects with chronic use

not the first drug of choice

takes up to 6 months to notice effects

May actually reverse the process and improve joints whereas NSAIDs do not reverse the process.

Question 19

Acetaminophen

Answer 19

does not inhibit COX-1 or COX-2 , it does interact with COX-3, this is why it can bring temperature down.

It produces a toxin metabolite which gets conjugated with glutathione and the problem is that with huge doses is can lead to hepatotoxicity. At risk is large use os EtOH and Hep C

Question 20

In Tylenol overdose give a molecule that does the job of glutathione which is

Answer 20

N-acetylcystein

Question 21

Tramadol mechanism

Answer 21

complex - may interact with opioid receptors and sertonergic receptors it is often times used in combination with NSAID’s to tackle inflammation and to help with pain.

Question 22

Gout is when the

Answer 22

uric acid crystals get engulfed by macrophages and cause severe pain. Injury can precipitate a gout attack.

Question 23

Treatment for acute gout attack

Answer 23

pain killer and anti-inflammatory

Question 24

chronic gout treatment

Answer 24

Allupurinol

Question 25

Allupurinol is an inhibitor of

Answer 25

Xanthine oxidase

Question 26

If uric acid is inhibited then concentration of hypoxanthine and xanthine will increase, but they are

Answer 26

water soluble

Question 27

Mechanism od Allopurinol

Answer 27

Xanthine oxidase “suicidal inhibitor” Allupurinol is not the inhibitor itself, but after conversion to Alloxanthine it actually inhibits the enzyme , so it inhibits the enzyme involved in its own metabolism.

Question 28

Colchicine

Answer 28

prevents migration of immune cells into joints which decrease inflammation. In smaller doses, it can treat chronic disease, but it does not have an analgesic effect.