COX inhibits

Question 1

What enzymes to prostaglandins activate

Answer 1

COX-1

COX-2

Question 2

What drugs counteract activity of COX-1 and 2

Answer 2

Aspiring
Ibuprofen
Celebrex
Acetaminophen

Question 3

COX -1 effects on the body
(3)

Answer 3

Always active - housekeeping chores

• Gastric protection (mucus production)
• Promoting Platelet aggregation
• Maintain Renal Vasodilation

Question 4

COX-2 effects on the body
(4)

Answer 4

Activated by tissue damage

• vasodilation
• inflammation/ pain
• fever
• colorectal cancer promotion

Question 5

COX-1 inhibition drugs
Beneficial and Adverse

Answer 5

Beneficial Effect:

• decrease platelet aggregation
• protects against MI and stroke

Adverse:

• bleeding
• gastric ulceration

Question 6

COX 2 inhibition drugs
Beneficial and Adverse effects

Answer 6

Beneficial:

• decreases inflammation, pain, fever
• protection against collateral cancer

Adverse:

• renal impairment
• vasoconstriction

Question 7

COX inhibitors: 2 groups

Answer 7

1) Anti-inflammatory properties
- NSAIDs (aspirin, ibuprofen, celecoxib)

2) Acetaminophen
- reduce pain and fever
- CANT SUPPRESS INFLAMMATION

Question 8

NSAIDs 2 groups

Answer 8

1) first generation

• inhibit both COX 1 and COX2
• suppress pain and inflammation but SERIOUS SIDE EFFECTS

2) second generation

• inhibit only COX 2
• in theory can suppress pain and inflammation
  -FEWER adverse effects than first

Question 9

Chemistry of Aspirin

Answer 9

belongs to chemical family of salicylic acids

produced by substituting an acetyl group into salicylic acid
–> acetylsalicylic acid (ASA)

Question 10

Mechanism of aspririn

Answer 10

inhibits COX-1 and COX-2

Question 11

aspirin inhibition of COX-1
Positive and negative

Answer 11

Positive: protection against MI and stroke

Negative: gastric ulceration, bleeding and renal impairment

Question 12

Inhibition of COX-2

Answer 12

Positive:
- decrease inflammation, pain, and fever
- vasoconstriction
- protection against colorectal cancer

Question 13

Is aspirin a reversible or irreversible inhibitor of COX

Answer 13

irreversible inhibitor

Question 14

Aspririn Pharmacokinetics

Answer 14

A: PO

D: ++ bound to albumin/ 20% delivered to body tissues and CNS

M: ASA reduced to salicylic acid in liver

E: salicylic acid excreted by the kidney

Question 15

Plasma therapeutic and toxicity levels

Answer 15

low- 100 mcg/ml
therapeutic- 150-300 mcg/ml
severe toxicity- 400 mcg/ml

Question 16

therapeutic uses aspirin (4)

Answer 16

1) mild moderate analgesia

2) fever reducer

3) rheumatoid arthritis and Osteoarthritis ** drug of choice

4) Suppression of platelet aggregation

• aspirin binds to cox 1 = suppresses platelt aggregation
• irreversible effect requires 8 days for platelets to reach normal levels
• daily aspirin recommended for ischemic stroke, acute MI, chronic angina

Question 17

aspirin adverse effects

Short term
Long term
Salicylism
Pregnancy

Answer 17

short term- low AE

long-term high doses- toxicity

Salicylism- tinnitus, sweating, dizziness
- symptoms stop once aspirin stopped

pregnancy
- anemia from GI blood loss
- postpartum hemorrhage

Question 18

acute poisoning of aspirin

Answer 18

respiratory depression

adults lethal dose: 20-25 gm

children 4 gm

Question 19

dose/ administration of aspirin

Answer 19

always PO
- dose with food/water

Question 20

Non-aspirin first-generation NSAIDS

Answer 20

ibuprofen *prototype

Question 21

Non-aspirin First generation NSAIDS mechanism
Reversible?

Answer 21

inhibit COX 1 and COX 2
BUT REVERSIBLE INHIBITION

Question 22

Non-aspirin First generation NSAIDS therapeutic uses

Answer 22

similar to aspirin
- decreased inflammation, pain, fever

Question 23

Ibuprofen compared to Aspirin

Answer 23

• less gastric bleeding
• less inhibition of platelet aggregation = greater risk MI and stroke

Question 24

Non-aspirin First generation NSAIDS drug interaction

Answer 24

similar to aspirin

Question 25

Reye Syndrome

Answer 25

rare, serious, swelling of liver and brain -affects children after viral infection - aspirin puts children at risk of these

Question 26

Second-Generation NSAIDs

Answer 26

COX-2 inhibitors - aka COXIBS

Question 27

why were COX 2 inhibitors developed

Answer 27

hypothesis that - selective inhibition of COX-2 should be able to suppress pain/inflammation but no risk gastric ulcertaion

Question 28

Selective COX-2 Inhibitors drug

Answer 28

Celecoxib

Question 29

Selective COX-2 Inhibitors mech

Answer 29

selective inhibition of COX-2 - primarily reduces painand inflammation

Question 30

Selective COX-2 Inhibitors pharmacokinetics A, D, Half life

Answer 30

PO- peaks in 3hours Extensive (97%) binding to plasma proteins Half-life 11 hours

Question 31

Selective COX-2 Inhibitors Adverse effects

Answer 31

well tolerated dyspepsia (upset stomach) and stomach pain pregnancy: don't use third trimester Cardiovasuvlar events

Question 32

how does celecoxib have increased risk MI and stroke?

Answer 32

1) does not inhibit COX-1 = does not inhibit platelet aggregation 2) does inhibit COX02 in blood vessels - increased risk of vasoconstriction Together = risk of vessel blockage, development of thrombis

Question 33

Second-Generation NSAIDs therapeutic uses

Answer 33

first selective COX-2 inhibitor to market reduce pain and inflammation indicated for RA, OA, juvenile idiopathic arthritis, pain and dysmenorrhea doesn't decrease aggregation = does not promote bleeding

Question 34

Acetaminophen

Answer 34

- similar to aspirin - aceta has analgesic, antipyretic like aspirin --> doesnt have anti-inflammatory

Question 35

Mechanism of Action acetaminophen

Answer 35

- limited to prostaglandin CNS inhibition of COX-1 and 2 --> can reduce fever and pain but not inflammation

Question 36

acetaminophen pharmacokinetics A,D, half life

Answer 36

PO/ peak in 3 hours extensive plasma binding Half-life 11 hours

Question 37

Drug interaction acetaminophen

Answer 37

Alcohol: regular alcohol consumption combined = greater risk liver damage Warfarin: increased bleeding Vaccines: blunt immune response to childhood vaccines

Question 38

Acture Toxicity: Liver Damage with acetaminophen

Answer 38

overdose is leading cause of acute liver failure low risk in normal therapeutic doses - except for ppl who drink alcohol or have liver disease

Question 39

therapeutic uses acetaminophen

Answer 39

relief of pain and fever Preferred to NSAIDs for children who have chickenpox or influenzas