NSAIDs_PHARM

Question 1

MOA
COX

Answer 1

Cyclooxygenase
- formation of prostanoids from AA

• prostaglandin E2 (PGE2)
• prostacycline (PGI2)
• Thromboxane A2 (TXA2)

Question 2

Function of
COX1

Answer 2

Found in all tissues
“housekeeping” or “good COX”

• Conversion AA to TXA2
• Platelet activation
• Aggregation and vasoconstriction
• Increase mucous, bicarb
• decrease acid
• increase GI blood flow
• Increase renal blood flow

Question 3

Function of COX2

Answer 3

Bad Cox

Blood vessels
- inflammation
- pain
- MI, stroke, clots

Gastric
- Colon cancer

Uterus
- uterine contractions

Renal
- increase blood flow

Brain
- fever, pain

Question 4

First generation COX inhibitors
List
MOA

Answer 4

1. Aspirin (irreversible COX inhibition)

ASA acetylsalicylic acid (aspirin)
magnesium salicylate
sodium salicylate
salsalate

2. Non-aspirin NSAID (reversible COX inhibition)
   ibuprophen
   naproxen
   indomethacin (*highest stroke risk)
   diclofenac
   * less gastric bleeding
   * superior dysmenorrhea

*trial and error
respond to 1 > than other
personalized response

Question 5

Second generation COX inhibitors
List
MOA

Answer 5

Inhibition COX2 only
Celecoxib

Question 6

Non- antiinflammatory COX inhibitor

Answer 6

Acetaminophen
COX inhibition in CNS only

Question 7

Indication
First generation NSAIDs

Answer 7

• pain
• fever
• inflammation
• dysmenorrhea

Question 8

Dosage
First generation NSAIDS

Answer 8

< 81mg anti-platelet
325 mg pain, fever, anti-platelet
>325mg inflamation

Question 9

MOA
first generation NSAIDs

Answer 9

Inhibition COX1 and COX2 and formation prostanoids (PGE2, PGI2, TXA2)

2. Analgesia
   - prevention formation prostaglandins (PGE2)
   - pain receptors not stimulated in PNS
3. Anti-pyretic
   - prevention prostaglandins in hypothalamus
   - hypothalamus set point stays the same
4. Anti-platelet aggregation
   - COX 1 inhibition
   - no TXA2
   - vasodilation, platelets remain inactivated
5. Anti-cancer (colon, breast, prostate)
   - COX 2 inhibition (promotes tumor growth and metastasis)
   - Cancer cells express high level of COX 2

Question 10

first generation NSAID
Contraindications

Answer 10

• PUD, bleeding, hemorrhages
• anti-coagulation, anti-platelets, Vitamin K deficiency, bleeding disorders
• angina pectoris, heart disease, CHF
• hypersensitivity
• hypertension BP > 150mmHg
• older adults (salicylism)
• children (reye’s syndrome)
• smokers
• alcoholism (> 3 drinks per day)
• kidney and liver disease
• pregnancy and breastfeeding

Question 11

first generation NSAID
SE

Answer 11

GI
- gastritis
- ulcers
- bleeds
- anemia

Rx.
PPI
H2 blocker
H. pylori urea breath test
D/C smoking, alcoholism, old age, PUD

Question 12

S&S of Salicylism

Answer 12

• tinnitus
• sweating
• head ache
• dizziness
• hypotension
• decreased LOC
• increase RR

Question 13

S&S Reye’s syndrome

Answer 13

• brain encephalopathy, decreased LOC
• fatty liver
• organ failure

Question 14

AE of NSAID and preganncy

Answer 14

• premature closure ductus artereosus
• ICH
• still birth
• ICH
• low birth weight
• anemia
• prolonged labour, hemorrhage

Question 15

Drugs to avoid on NSAIDS

Answer 15

• anti-platelets
• anti-coagulants
• glucocorticoids
• alcohol
• smoking
• ACE inhibitors, ARBs (renal failure)
• vaccinations

Question 16

Contraindication NSAIDs

Answer 16

infants
children (reye’s syndrome)
older (salicylism, CHF, renal failure, BP)
pregnancy (ductus arteriosus, still birth)

Question 17

Rules for prescribing NSAID

Answer 17

• lowest dosage
• shortest time
  personalized response to first generations NSAIDs (trial and error)
  irreversible inhibition aspirin
  aspirin = no to infants/children, higher bleeding risk
  non-aspirin = MI and stroke increased risk, SJS

Question 18

SE
non-aspirin NSAID

Answer 18

• less GI bleeding
• MI, stroke
• SJS

Question 19

Second generation COX
list
MOA

Answer 19

Celecoxib
inhibition COX2
- GI: decrease mucous, bicarb, increase acid, decrease blood flow
- kidney: decrease blood flow
- decrease PGE2 (Pain, fever, inflammation), PGI2 (decrease vasodilation)
- cancer: decrease solid tumor growth
- uterus: decrease contraction

Question 20

Celecoxib
SE

Answer 20

GI
- gastritis
- GI bleeding

CV
- MI, stroke, angina, CHF precipitation

Kidney
- kidney failure

Question 21

Contraindications/caution
Celecoxib

Answer 21

• heart disease, angina
• kidney disease
• PUD, GI bleeding
• sulfa allergies
• pregnancy/breast feeding/ children

Question 22

prophylactic prescription NSAIDs

Answer 22

PPI
- proton pump inhibitor

H2 blocker
- histamine 2 blocker
- increase mucous, bicarb, decrease acid

Question 23

Example
Non-antiinflammatory NSAID

Answer 23

Acetaminophen
- inhibition COX in CNS
- not in the PNS
- no effect on inflammation

Question 24

Indication for
first generation NSAIDS

Answer 24

• pain
• fever
• inflammation
• anti-platelet
• cancer

Question 25

Indication for
Second generation NSAID

Answer 25

FAP (familial adenomatous polyposis)
RA, OA, ALS

Question 26

Acetaminophen MOA

Answer 26

blockage COX in CNS
1. antipyretic
2. analgesia

*not for inflammation

Question 27

Acetaminophen daily dosage limit

Answer 27

4 g per day
< 3 g per day (fasting, anorexia, alcoholism)

Question 28

Leading cause of liver failure

Answer 28

acetaminophen overdose

Question 29

S&S acetaminophen overdose

Answer 29

48 hours post ingestion
sweating, nausea/vomitting/diarrhea, RUQ painAn

Question 30

Antidote for acetaminophen overdose

Answer 30

acetylcysteine
must be given < 24 hour mark
glutathione substitutionL

Question 31

Pathway metabolism Acetaminophen in the liver

Answer 31

1. major pathway
   - glutathione conjugation
2. minor pathway
   - cyp450 enzyme
   - toxic metabolite formation
   - liver failure/damage
   *alcoholics
   *acetaminophen overdose
   *anorexia

Question 32

SE of acetaminophen

Answer 32

• liver inflammaiton/failure
• SJS, TENS, AGEF
• hypertension
• rebound head aches

Question 33

Safety acetaminophen

Answer 33

• safe in renal failure, old, young, pregnancy