Cyclooxygenase Inhibitors

Question 1

4 types of analgesic product

Answer 1

aspirin
ibuprofen
naproxen
acetaminophen

Question 2

COX-1 (good COX) targets

Answer 2

1. Platelets: synthesis of TXA2 which stimulates platelet aggregation
2. Stomach: synthesis of PGE2 and PGI2 which are gastroprotective
3. Kidneys: synthesis of PGE2 and PGI2 which stimulate renal vasodilation and blood flow

Question 3

Effects of COX-2 (bad COX)

Answer 3

• inflammation, pain, fever
• uterus contractions at term
• bronchial smooth muscle relaxation

Question 4

Aspirin is a unique first generation NSAID in that..

Answer 4

COX inhibition is irreversible

Protection against CV events due to COX-1 inhibition

Question 5

Therapeutic Uses of Aspirin

Answer 5

a. anti-inflammatory (high doses - 4-6g/day)
b. analgesic (325-1000mg, 3-4x/day)
c. antipyretic (325-1000mg, 3-4x/day)
d. dysmenorrhea (325-1000mg, 3-4x/day)
e. antiplatelet* (81mg daily)

Question 6

Reye’s syndrome

Answer 6

complication with the use of Aspirin in children under 18 years old

causes encephalopathy and fatty liver

greatest risk if used post-viral illness

Question 7

Hypersensitivity reaction in the use of NSAIDs

Answer 7

inhibition of COX results in shunting of production away from prostaglandins towards leukotrienes

leukotrienes cause bronchial constriction

Question 8

ASA contraindications

Answer 8

• peptic ulcer disease
• bleeding disorders
• NSAID hypersensitivity
• under 18yo
• 3rd trimester of pregnancy

Question 9

3 key exceptions of side effects of OTHER first generation NSAIDs vs Aspirin

Answer 9

1. risk of CV even is increased
2. no salicylism
3. not linked to Reye’s syndrome

Question 10

Salicylism

Answer 10

results from creation of salicylate compounds causing tinnitus, sweating, headache and dizziness

only with aspirin

Question 11

Second generation NSAIDs

Answer 11

selectively inhibits COX-2

Question 12

Side effects of coxibs (second generation NSAIDs)

Answer 12

a. GI ulceration

b. HIGHEST risk of CV events

Question 13

NSAIDs and Hypertension

Answer 13

may cause or exacerbate HTN

- causes edema and fluid retention

Question 14

acetaminophen

Answer 14

inhibition of COX in CNS, not periphery

• analgesic, antipyretic
• NO anti-inflammatory activity
• NO effect on kidneys or platelets
• can cause liver toxicity when overdosed

Question 15

Metabolic pathways of Acetaminophen

Answer 15

a. major pathway
- conjugated to form nontoxic metabolites

b. minor pathway
- converted into toxic metabolite by CYP450&raquo_space; converted into non-toxic form by glutathione

Question 16

Three conditions that can deplete glutathione

Answer 16

• alcohol consumption
• malnutrition
• acetaminophen overdose

Question 17

Alcohol and Acetaminophen increase risk of liver damage in three ways

Answer 17

1. CYP450 induction&raquo_space; more toxic metabolite
2. depletes glutathione
3. pre-existing liver damage reduces tolerance to insult

Question 18

early and late symptoms of alcohol+acetaminophen interaction

Answer 18

EARLY:
n/v
diarrhea
sweating

LATE: hepatic failure, coma, death

Question 19

what is acetylcysteine used for?

Answer 19

alcohol+acetaminophen interaction antidote

• repletes glutathione stores