NSAIDS

Question 1

Aspirin

Answer 1

Aspirin

Salicylate

Question 2

NSAIDs

Answer 2

Ibuprofen
Naproxen
Acetaminophen
Celecoxib

Question 3

GI protective

Answer 3

Misoprostol

Question 4

NSAIDs treat :

Answer 4

SYMPTOMS only

Question 5

NSAIDS block

Answer 5

Cyclooxygenase pathway to make prostaglandins

Question 6

Eicosanoids

Answer 6

*bind to receptors on cell membrane
*From AA (omega6)
Prostaglandins, thromboxanes, leukotrienes
*short half life

Question 7

COX -1

Answer 7

• constitutive expression
• housekeeping
• inhibition - GI side effects

Question 8

COX- 2

Answer 8

• induced
• renal problems w/ inhibition - renal perfusion down
• make prostanoids at inflammation sites (cancer)

Question 9

What can be liberated during stress?

Answer 9

EPA, AA

Question 10

PGE2 does…

Answer 10

• Up body temp
• inflammation
• protective against peptic ulcer
• less platelet function

Question 11

TXA2 does

Answer 11

• UP Platelet agregation from COX -1 (in platelets)

* Vasoconstriction/Bronchoconstriction

Question 12

Arachidonic Acid Pathway

Answer 12

Stimulus –> phospholipase A2 –> Phospholipids –> arachidonic acid –> Eicosanoids

Question 13

Phospholipase A2

Key step in inflammatory pathway

Answer 13

Phospholipase A2 –> hydrolyze fatty acids in cell membrane INNER layer

• Arachidonic Acid (AA)=Omega6
• Eicosapentaeoic Acid (EPA)=Omega3

Question 14

Prostanoids

how synthesized?

Answer 14

From isomerases/transferases

• Platelets = TXA2 (from Cox 1)
• Activated Macrophages = TXA2/PGE2 (from Cox 2)

Question 15

PGI2

Answer 15

• made from vascular epithelium
• LOWER platelet aggregation
• Vasodilation

Question 16

NSAIDs inhibit Cox 1 + 2

Answer 16

Aspirin
Ibuprofen
Naproxen
Piroxicam

Question 17

NSAIDs inhibit COX-2

Answer 17

Celecoxib (CV risk)

*Less GI toxicity

Question 18

NSAID

Excretion?

Answer 18

Renal

Question 19

NSAID

Type of inhibition

Answer 19

*Reversible competitive inhibitor of Cox 1 + 2
(Not like aspirin!-irreversible)
*inhibit prostaglandin synthesis

Question 20

NSAIDs

Tx effects

Answer 20

Low dose -

• Analgesia
• Antipyretic

High dose -

• anti-inflammatory
• close patent ductus arteriosus

Question 21

Anti inflammatory dose

Answer 21

Ibuprofen - 400-800mg 6-8hr

Aspirin - 4-5g per day

Question 22

How possibly can Nsaid protect from cancer?

Answer 22

Cox-2 inhibition, stopping constant inflammation

Question 23

NSAID

S.E.

Answer 23

• GI - aspirin more
• renal - less clearance, proteinuria, analgesic nephropathy (w/ UTIs)
• NO w/ pregnant! (Acetaminophen OK)

Question 24

NSAID drug interactions

Answer 24

• Ibuprofen impairs aspirin’s ability to acetylate COX

* NO w/ ace inhibitor

Question 25

How is aspirin special?

Answer 25

IRREVERSIBLE cox 1 + 2 inhibitor

Question 26

Aspirin Uses

Answer 26

* analgesic * antipyretic * anti-inflammatory (irreversible inhibition of cox 1 + 2) *cardio (low dose = less platelet clumping). (TXA2 inhibited!)

Question 27

Aspirin metabolized in liver to

Answer 27

Salicylate ! (Reversible competitive COX inhibitor) *PCT/glomerular filtration excretion

Question 28

Aspirin S.E.

Answer 28

``` SAME AS all *gi *renal - analgesic neuropathy, less perfusion *less urate excretion - low dose More urate excreation - high doses *hypersensitivity (all NSAIDs) ```

Question 29

Aspirin Toxicity

Answer 29

Tinnitus Respiratory/met acidosis (Alkalosis at normal levels)

Question 30

Ibuprofen Half life

Answer 30

Short 2h, take frequently

Question 31

Ibuprofen w/ aspirin?

Answer 31

Lower cardioprotective effects

Question 32

Naproxen

Answer 32

Half life 14 hrs | *rheumatoid arthritis, etc.

Question 33

Celecoxib

Answer 33

* Only Cox 2 inhibitor * HTN /thrombosis risk- not in HF/CVA patients * sulfa-sensitve

Question 34

Mechanical damage - inflammatory response cascade

Answer 34

PHOSPHOLIPASE A2 - activates to hydrolize fatty acids on INNER LAYER of cell membrane to make AA + EA

Question 34

Prostanoids

Answer 34

Synthesized due to COX 1 + 2 Certain cells have certain Prostanoids

Question 34

EPA + AA metabolized into what ecosanoids?

Answer 34

* EPA - 3 ecosanoids | * AA - 6 ecosanoids (more potent)

Question 34

Eicosanoid functions

Answer 34

* Vasodilation * Bronchoconstriction * PGI2-LESS platelet aggregation * Thomboxane- MORE platelet aggregation

Question 35

w-3 Fatty acids lessen inflammation by

Answer 35

1) less AA to make w-6 2) compete with AA for COX,LipoOX 3) compete with w-6 for receptors

Question 36

NSAIDs inhibit

Answer 36

C

Question 37

PGI2 does...

Answer 37

* from vascular epithelium | * LESS platelet aggregation

Question 38

Aspirin Allergy

Answer 38

* Often w/ nasal polyp people | * Cross with ALL NSAIDs

Question 39

How does Cox 2 inhibitor UP CV risk?

Answer 39

COX-2 inhibit -->up PGI2 --> LESS platelet aggregation. JUST FUCKING REVIEW THIS SLIDE

Question 40

GI protective agent to add to Aspirin/NSAIDS

Answer 40

Misoprostol * PGE1-like - stop acid secretion, stop peptic ulcer * PREGGER! +Mifepristone - terminate early

Question 41

Acetaminophen

Answer 41

Oral, iv NO ANTI-INFLAMMATORY Large dose - liver toxic, glucorination+sulfation saturated, no excretion

Question 42

Acetaminophen toxicity

Answer 42

CYP2E1 induction

Question 43

Acetaminophen OD Tx

Answer 43

Mucomyst | N-acetylcystein