Exam 3: NSAID analgesics

Question 1

What do COX enzymes produce?

Answer 1

Prostaglandins, thromboxane, prostacyclin

Question 2

What is the effect of prostaglandins?

Answer 2

vasodilation, gastric cytoprotection, nociceptor sensitization

Question 3

What is the effect of thromboxanes?

Answer 3

promotes platelet aggregation, inflammation

Question 4

What is the effect of prostacyclins?

Answer 4

Inhibits platelet aggregation, vasodilation, gastric cytoprotection

Question 5

T/F: COX1 enzymes are for normal physiology, COX2 enzyme is induced by acute inflammation?

Answer 5

True

Question 6

What COX enzymes do NSAIDs target?

Answer 6

Both COX1 and COX2

Question 7

Which irreversibly inhibits COX1 and COX2 enzymes: Aspirin or other NSAIDs

Answer 7

Aspirin

Question 8

How do NSAIDs reverse the peripheral sensitization of nociceptors?

Answer 8

By blocking prostaglandin synthesis

Question 9

What leads to increase in body temperature?

Answer 9

induction of COX2 and PGE2 synthesis in epithelial cells of brain vasculature

Question 10

What causes the side effect of gastric bleeding/ulcers in patients who overuse NSAIDs?

Answer 10

inhibition of prostaglandins and prostacyclins, which both inhibit secretion of gastric acid and promote secretion of mucus, leads to less epithelial protection

Question 11

How does aspirin lead to nephrotoxicity?

Answer 11

vasoconstriction by blocking COX-2 enzymes

Question 12

How does aspirin lead to electrolyte disturbances?

Answer 12

causes respiratory alkalosis (via hyperventilation), and metabolic acidosis (uncoupling oxidative phosphorylation, leading to increased lactic acid)

Question 13

What are signs of a mild aspirin toxicity?

Answer 13

Tinnitus (increased arachidonic acid sensitizes NMDA receptors on cochlear nerve), headache, nausea, sweating, thirst, hyperventilation

Question 14

What are signs of severe overdose to aspirin?

Answer 14

Hyperventilation, acid-base imbalance, dehydration, agitation, hyperactivity, slurred speech, fever

Question 15

What is the treatment of an aspirin overdose?

Answer 15

Induce vomiting, use sodium bicarb to increase systemic pH, dialysis

Question 16

Is hypersensitivity to aspirin immune-mediated

Answer 16

no

Question 17

what is the likely cause of aspirin hypersensitivity?

Answer 17

shifting of arachidonic acid to lipoxygenase that increases leukotriene-mediated effects (bronchial constriction, increased secretion, edema, etc)

Question 18

What is the treatment for aspirin hypersensitivity?

Answer 18

Epinephrine, avoid NSAIDs

Question 19

How does low dose of aspirin guard against heart attacks?

Answer 19

preferentially inhibits synthesis of thromboxanes

Question 20

Describe ibuprofen

Answer 20

Analgesis, antipyretic, anti-inflammatory, fewer GI effects than aspirin, clotting effects are reversible

Question 21

Describe indomethacin

Answer 21

Triple-A, most potent COX inhibitor, significant toxicity (GI distress, abdominal pains)

Question 22

What can indomethacin be used to treat (congenital disorder)

Answer 22

Patent ductus arteriosus

Question 23

Describe Ketorolac

Answer 23

NSAID, can be injected, can replace or reduce opioid dose if addiction is an issue

Question 24

What COX enzyme does celecoxib inhibit?

Answer 24

selective COX2 inhibitor

Question 25

Describe acetaminophen

Answer 25

NOT ANTI-INFLAMMATORY, but it is an analgesic, antipyrretic, could target hypothalamus, low side effects

Question 26

what is the problem with acetaminophen toxicity

Answer 26

much lower therapeutic index, metabolism can cause free radical in the liver

Question 27

How do you treat acetaminophen toxicity?

Answer 27

N-acetylcysteine as a scavenger drug (similar to glutathione)