NSAIDs Pathway

Question 1

When injury occurs, what is the pathway that is activated?

Answer 1

Phospholipase A2

Question 2

Activation of phospholipase A2 catalyzes hydrolysis of…

Answer 2

Arachidonic acid from phospholipids in the cell membrane

Question 3

What do NSAIDs do to this pathway?

Answer 3

Inhibit cyclooxygenase enzymes

Question 4

NSAIDs
- inhibit cyclooxygenase

Answer 4

Inhibits prostaglandins (PGs) synthesis with both beneficial and unwanted effects

Question 5

Cyclooxygenase enzyme

Answer 5

Converts Arachidonic acid to prostaglandins (PGs) and thromboxane A2

Question 6

Prostacyclin (PGI)

Answer 6

Released from vascular endothelial cells to prevent platelet aggregation

Question 7

Thromboxane A2

Answer 7

Stimulates platelet aggregation when blood vessels are injured

Question 8

Other PGs

Answer 8

PGE1
PGE2
PGE2a

Question 9

Other PGs are involved in

Answer 9

Pain
Inflammation
Fever
GI cytoprotection
Vasodilation
Maintain renal blood flow

Question 10

NSAIDs inhibit cyclooxygenase (COX) pathway
- increasing what?

Answer 10

Lipoxygenase pathway

Question 11

NSAIDs inhibit cyclooyxgenase
- increasing lipoxygenase pathway

Answer 11

Those with respiratory disease become more susceptible to bronchospasm

Question 12

5-lipoxygenase enzyme

Answer 12

Converts arachidonic acid to leukotrienes

Question 13

Leukotrienes

Answer 13

Mediate allergy-induced bronchoconstriction

Question 14

Where are leukotrienes produced?

Answer 14

Mainly in inflammatory cells (mast cells, basophils, eosinophils, macrophages and polmorphonuclear leukocytes)

Question 15

What blocks 5-lipoxygenase

Answer 15

Zileuton- anti-asthmatic agen

Question 16

What blocks leukotriene receptors

Answer 16

Montelukast (singulair) and zafirlukast
- controlling the symptoms of asthma and bronchoconstriction

Question 17

COX-1

Answer 17

Expressed in the stomach to produce PGs

Question 18

COX-1
- PGs produce?

Answer 18

Cyotprotectin in the GI tract by inhibiting gastric acid secretions
Increasing bicarbonate release
Promoting mucus secretion

Question 19

NSAIDs inhibit what?

Answer 19

Both COX-1 and COX-2 enzymes

Question 20

Non-selective NSAIDs
- inhibitation of COX-1

Answer 20

GI side effects
bleeding
Gastric ulcers

Question 21

COX-2 inhibitors

Answer 21

Spare COX-1 induced synthesis of PGs, preserving the integrity of the lining of the GI tract

Question 22

MOA of NSAIDs

Answer 22

Blockade of prostaglandin synthesis via inhibition of the enzyme cyclooygenase (COX)

Question 23

Nonselective COX-1 and COX-2 inhibitors

Answer 23

Acetylsalicyclic acid (asprin)
Ibuprofen
Naproxen

Question 24

NSAIDs properties

Answer 24

Antipyretic
Analgesic
Anti-inflammatory

Question 25

Aspirin (acetylsalicylic acid)

Answer 25

Covalently binds and irreversibly inhibits COX-1 and COX-2 enzymes of the platelets (prevents platelet aggregation)

Question 26

Single dose of aspirin will..

Answer 26

Inhibit platelet COX for 8-11 days (life of the platelet)

Question 27

Adverse effects and contraindications of Aspirin

Answer 27

High doses cause salicylism (tinnitus, vertigo, hearing loss) Contraindicated in children and teenagers with chickenpox and influenza

Question 28

Adverse effects and contraindications - Chickenpox and influenza

Answer 28

Tied to Reye's disease, which is a potentially fatal disease accompanied by liver damage and encephalopathy

Question 29

When should patients stop taking aspirin?

Answer 29

One week prior to surgery or dental procedures d/t tendency of aspirin increasing clotting time and cause excessive bleeding

Question 30

When taking Aspirin what do you avoid?

Answer 30

Taking it during pregnancy and breast-feeding

Question 31

Non-selective COX inhibitors

Answer 31

Ibuprofen (Motrin-OTC, Advil-OTC) Naproxen (aleve-OTC, Naprosyn)- longer half-life Ketorolac

Question 32

Ketorolac

Answer 32

Moderate to severe pain and limited to 5 day treatment Increased incidence of peptic ulcers

Question 33

Ketorolac - Do not use with who?

Answer 33

Patients with renal impariement

Question 34

Celecoxib (celebrex)

Answer 34

Less GI bleeding/irritation

Question 35

Celecoxib - Contraindications

Answer 35

Patients allergic to sulfonamides Avoid in patients with Renal, CV, and cerebrovascular disease (increased risk of heart attack and stroke)

Question 36

Celecoxib inhibits

Answer 36

CYP2D6 resulting in severe drug interactions

Question 37

Acetaminophen MOA

Answer 37

Unclear

Question 38

Acetaminophen effects

Answer 38

Analgesic and antipyretic

Question 39

Acetaminophen is a weak

Answer 39

COX-1 and COX-2 inhibitor in peripheral tissues

Question 40

Not an NSAIDs

Answer 40

Acetaminophen bc it lacks anti-inflammatory or anti-platelet effects

Question 41

Clinical uses of acetaminophen

Answer 41

Mild to moderate pain (HA, myalgia, postpartum pain)

Question 42

Acetaminophen is preferred for what?

Answer 42

During pregnancy and breastfeeding

Question 43

Where is acetaminophen metabolized

Answer 43

Liver

Question 44

What is generated?

Answer 44

minor toxic metabolite that is conjugated to glutathione in the liver and excreted in the kidney

Question 45

Acetaminophen - Overdose or standard dose patients with liver impairment

Answer 45

Toxic metabolite accumulates and induces liver damage Hepatic renal tubular necrosis may occur

Question 46

How to treat overdose of acetaminophen

Answer 46

Use n-acetylcysteine within 8 hours of overdose bc it binds to the toxic metabolite and counteracts acetaminophen toxicity

Question 47

Acetaminophen

Answer 47

Tylenol