NSAIDs

Question 1

NSAIDs have what activities?

Answer 1

3 A’s:
antipyretic
analgesic
anti-inflammatory

Question 2

Mechanism of NSAIDs (general)

Answer 2

inhibits COX –> inhibition of prostaglandins and thromboxanes

Question 3

Eicosanoids synthesis:

Answer 3

PLA2 receptor makes arachidonic acid which makes:

1. Cyclooxygenases
   - Prostaglandins
   - Prostacyclin
   - Thromboxane
2. Lipooxygenases
   - Leukotrienes

Question 4

COX-1

Answer 4

• involved in tissue homeostasis

- dominant in gastric epithelial cells and main source of protective prostaglandin formation

Question 5

COX-2

Answer 5

major source of eicosanoids in inflammation and cancer

• kidney and brain
• endothelial COX-2 primary source of vascular prostacyclin

Question 6

Anti-inflammatory action of NSAIDs is mainly related to _____

Answer 6

inhibition of COX-2

Question 7

Gastric damage is due to ___

Answer 7

inhibition of COX-1

Question 8

Nonselective COX inhibitors

Answer 8

As Dogs I Invented Kissing No Problem (ADIIKNP)

Aspirin
Diclofenac
Ibuprofen
Indomethacin
Ketorolac
Naproxen
Piroxicam

Question 9

COX-2 selective inhibitors

Answer 9

Cool Mom (CM)

Celecoxib
Meloxicam

Question 10

NSAIDs uses

Answer 10

• pain
• inflammation
• arthritis
• colon cancer*
• niacin tolerability*
• closure of ductus arteriosus*

Question 11

Niacin tolerability and NSAIDs

Answer 11

Niacin lowers cholesterol levels –> intense flushing

flushing mediated by PGD2 which can be inhibited with NSAID

Question 12

AE of NSAIDs

Answer 12

• GI
• CV
• Renal
• NERD (respiratory disease)

Question 13

GI adverse effects

Answer 13

due to:

• inhibition of COX-1 in gastric epithelial cells
• ulceration by local irritation of gastric mucosa

Question 14

How due you treat the gastric damage and gastric uclers caused by NSAIDs?

Answer 14

• misoprostrol
• proton pump inhibitors
• H2 blockers

Question 15

Lowest risk GI AE drug?

Answer 15

Celecoxib

Question 16

Highest risk GI AE drug?

Answer 16

Piroxicam

Question 17

CV AE

Answer 17

caused by imbalance of TXA2 and PGI2

• can lead to vasoconstriction, platelet aggregation, and thrombosis
• more COX-2 selective NSAIDs = higher risk

Question 18

TXA2

Answer 18

promotes platelet aggregation

vasoconstriction

Question 19

PGI2

Answer 19

inhibits platelet aggregation

vasodilator

Question 20

Highest risk of CV AE drug?

Answer 20

Celecoxib

Question 21

Renal AE

Answer 21

• decrease renal blood flow

- analgesic nephropathy

Question 22

Why is a decrease in renal blood flow that detrimental?

Answer 22

Pt with CHF, CKD, etc = problem bc PGs are really important in maintaining GFR

ALSO, NSAIDs can elevate BP and cause fluid retention –> worsen kidney function

Question 23

NSAIDS effect on RBF in pt with CHF, CKD, etc.

Answer 23

inhibition of PG decreases afferent flow to glomerulus and decreases GFR

Question 24

Chronic interstitial nephritis is cased by___

Answer 24

prolonged and excessive use of analgesics

associated with phenacetin

Question 25

COX-2 is active in which organ?

Answer 25

Kidney- which can cause renal toxicities

Question 26

NERD symptoms

Answer 26

- angioedema - bronchial asthma - flushing - hypotension - shock

Question 27

NERD causes

Answer 27

increase leukotrienes by COX inhibition

Question 28

Celecoxib other AE

Answer 28

hypersensitivity reactions (like rashes)

Question 29

NSAIDs drug interactions

Answer 29

- ACE inhibitors - Diuretics - Corticosteroids - Warfarin

Question 30

DI with ACEI

Answer 30

ACE-I prevent break down of kinins that stimulate PG

Question 31

DI with diuretics

Answer 31

effects are reduced by NSAIDs

Question 32

What is the triple whammy?

Answer 32

risk of acute kidney injury when ACEI or ARB is combined with diuretic and NSAID why? NSAID constrict afferent = reduce GFR ACEI and ARB dilate efferent = reduce GFR pt on combination should be monitored for creatine and potassium lvls

Question 33

DI with corticosteroids

Answer 33

increase GI ulcers

Question 34

DI with warfarin

Answer 34

increased risk of bleeding

Question 35

Contraindications

Answer 35

- Reye's syndrome - children/YA under 20 with fever and viral illness --> can use Acetaminophen and Ibuprofen instead - pregnancy

Question 36

Aspirin vs other salicylates

Answer 36

aspirin irreversibly acetylates while the others are reversible

Question 37

All salicylates

Answer 37

- Aspirin - Mg salicylate - Na salicylate - Salicyl salicylate

Question 38

Aspirin and salicylate actions

Answer 38

- uncouple oxidative phosphorylation --> elevated CO2 and increased respiration --> hyperventilation - inhibits TXA2 in platelets = long bleeding time - low dose aspirin inhibits COX-1 but not COX-2 so PG synthesis is unaffected

Question 39

High doses of aspirin are used to treat children during?

Answer 39

Acute phase of Kawasaki disease

Question 40

Salicylates at high and low doses:

Answer 40

high- anti-inflammatory | low- analgesic and antipyretic, also used for cardioprotective effects

Question 41

Aspirin metabolism

Answer 41

- hydrolyzed in tissue and blood - low doses can be converted into hydrosoluble conjugates by liver and excreted in kidney - half life is 3.5 hours - first order kinetics - 1g dose or more --> zero order kinetics

Question 42

Aspirin and salicylates AE

Answer 42

``` epigastric distress prolonged BT Reye's syndrome NERD Reduce uric acid secretion at low doses* Hepatic injury at high doses* ```

Question 43

Salicylism

Answer 43

intoxication - headache - mental confusion - hyperventilation - resp alkalosis and metabolic acidosis

Question 44

Acetaminophen

Answer 44

- analgesic and antipyretic | - no anti-inflammatory or antiplatelet effects

Question 45

Acetaminophen uses

Answer 45

- osteoarthritis - children - pregnancy - pain

Question 46

Acetaminophen AE

Answer 46

hepatotoxicity- liver failure administer Acetylcysteine