NSAIDs

Question 1

Prostaglandins are synthesized by what type of cells?

Answer 1

Endothelial cells

Question 2

Anti-platelet effects are exerted through inhibition of which type of COX?

Answer 2

COX-1

Question 3

High levels of prostaglandin (PGE2) inhibit platelet aggregation. T or F

Answer 3

True. However low levels of PGE2 enhance platelet aggregation along with thromboxane

Question 4

What are the actions of prostaglandin (PGE2)?

Answer 4

• Vasodilation
• Increase GFR through vasodilation
• Inflammation, Pain, Fever

Question 5

Low dose aspirin preferentially inhibit which COX?

Answer 5

COX-1

Question 6

NSAIDs are very effective for which type of pain?

Answer 6

Dull, throbbing pain

Not very good for acute pain

Question 7

What are the main prostanoids involved in nociceptor sensitization?

Answer 7

Prostaglandin E2 and Prostacyclin (PGI2)

Question 8

Why do we think NSAIDs also have a central site of action?

Answer 8

When administered intrathecally, ASA exerts equianalgesic effect as when administered systematically –> Strong evidence for spinal cord site of action exerted by ASA and other NSAIDs

Question 9

Explain the physiological process of fever.

Answer 9

Exogenous pyrogen (bacterial toxins) and cytokines stimulate endothelial cells in the hypothalamus to make PGE2. PGE2 increases the hypothalamic temperature set point resulting in fever.

Question 10

How does NSAIDs have antipyretic effect?

Answer 10

It inhibits PGE2 production, changing the hypothalamic temp. set point back to normal.

Question 11

Why were COX-2 selective NSAIDs designed?

Answer 11

To target pain and inflammation without significantly affecting COX-1 mediated homeostatic mechanisms such as GI protection

Question 12

Explain the physiological process of gout.

Answer 12

Gout is caused by excessive levels of uric acid in the blood which forms monosodium urate crystals and collects around the joints, tendons, and tissues causing inflammation and pain.

Question 13

In gout, urate crystals are phagocytosed by ________ which then release _________.

Answer 13

Synoviocytes, Prostaglandin

Question 14

NSAIDs MOA in gout

Answer 14

Inhibit urate crystal phagocytosis by inhibiting migration of leukocytes to the area and inhibiting prostaglandin production.

Question 15

Which drug can cause more uric acid build up, worsening gout?

Answer 15

Low dose aspirin

Question 16

What is the onset of action of Indomethacin?

Answer 16

2-4 hours

Question 17

How long does it take for swelling to decrease after starting indomethacin for gout?

Answer 17

3-5 days

Question 18

Distribution characteristic of NSAID

Answer 18

Highly protein bound

Question 19

Excretion of NSAID

Answer 19

excreted by glomerular filtration or tubular secretion

Question 20

What is the evidence for COX-2 selective NSAID and increase in CV risk?

Answer 20

Currently chances of CV events are the same as non-selective in subjects without prior diagnosis of CV disease

Question 21

NSAID does not increase the risk of A-fib. T or F

Answer 21

False. Same risk in selective and non-selective

Question 22

Low dose ASA MOA

Answer 22

preferential blockade of thromboxane A2 production causing decrease platelet aggregation and vasodilation

Question 23

List the risk factors for GI ulcer

Answer 23

• History of ulcer and ulcer complications
• Over age of 60
• High dose NSAID
• Multiple NSAID use
• Long-acting NSAID use
• Concomitant anticoagulants
• Heart disease

Question 24

What are the long-acting NSAIDs?

Answer 24

Piroxicam, Ketorolac, SR formulations

Question 25

Which 2 NSAIDs are associated with the lowest risk of GI ulceration?

Answer 25

ibuprofen and celecoxib

Question 26

All NSAIDs inhibit platelet aggregation to some extent. T or F

Answer 26

True

Question 27

What are the effects of NSAIDs on renal?

Answer 27

Salt and water retention; edema; hyperkalemia, worsening renal function and nephrotoxicity

Question 28

In the kidney, prostaglandin mediates _____ arteriole vaso____.

Answer 28

Afferent arteriole vasodilation

Question 29

In the kidney, angiotensin II mediates _____ arteriole vaso_____.

Answer 29

Efferent arteriole vasoconstriction

Question 30

If you have high CV risk, which NSAIDs can you use?

Answer 30

Naproxen if low GI risk or add PPI/misoprostol if moderate

Question 31

If you have high GI risk but low CV risk, what NSAID should you take?

Answer 31

Avoid NSAID | If must take, celecoxib + PPI

Question 32

When should you recommend a PPI or misoprostol?

Answer 32

To patients with moderate risk = 1-2 factors: | age, high dose NSAID, previous ulcer, use of ASA or antiplatelet drug

Question 33

What is the dose per kg that can cause ASA toxicity?

Answer 33

200mg/kg

Question 34

What are symptoms of salicylism?

Answer 34

Vomiting, tinnitus, decrease hearing, vertigo (reversible)

Question 35

What can be used to treat ASA toxicity?

Answer 35

Activated charcoal, gastric lavage

Question 36

Which proposed MOA of APAP can explain why it is not associated with inhibition of platelet aggregation?

Answer 36

APAP is a reducing agent that changes COX to its inactive form in cells with low oxidant status. Platelets have high oxidant status so APAP does not work there.

Question 37

Peroxide concentrations are high in the brain so that's why APAP works there. T or F

Answer 37

False, APAP works in the brain because it has low peroxides. Peroxides block APAP actions.

Question 38

Naloxone injected intrathecally can reverse the antinociceptive effects of acetaminophen. (T or F)

Answer 38

Partly true. It can reverse it if APAP was injected into the brain and spine at the same time. But not if given to the spine alone.

Question 39

95% of APAP metabolites are produced these 2 pathways.

Answer 39

Glucuronidation and sulfation

Question 40

Which CYP enzymes are involved in APAP metabolism?

Answer 40

CYP3A4 and CYP2E1

Question 41

Hepatotoxicity from APAP overdose can show up after ____ hours.

Answer 41

24-36

Question 42

What drug can you use to treat APAP toxicity?

Answer 42

Acetylcysteine - a glutathione substitute

Question 43

What is an important drug interaction of APAP?

Answer 43

Warfarin - enhances anticoagulation

Question 44

TRPV1

Answer 44

Transient receptor potential vanilloid 1 = activating this receptor in PAG in rats resulted in antinociception

Question 45

Which 2 descending pain inhibitory pathways is it theorized that APAP is involved in?

Answer 45

Serotonergic descending pain inhibitory pathway originating in the periaqueductal gray and descending endogenous opioid pathways