CoX inhibitors, NSAIDs, Aspirin, Acetaminophen

Question 1

describe the COX-1 and COX-2 pathways

Answer 1

Video notes

Question 2

which physiologic process is responsible for analgesia, anti-inflammatory activity, antipyeresis, bleeding tendencies, and gastric mucosal damage

Answer 2

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Question 3

explain the expected outcomes if a medication inhibits COX 1 and/or COX 2

Answer 3

If a medication inhibits COX 1:
gastric erosision and ulceration, bleeding, renal impairment but also protection against MI/stroke

If a medication inhibits COX 2:
renal impairment, promotion of MI and stroke, but also suppression of inflammation, alleviation of pain, reduction of fever and protection against colorectal cancer.

Question 4

After cellular damage, what role does cyclooxygenase play in the cascade leading to inflammation?

Answer 4

it catalyzes the synthesis of prostaglandins, which promote inflammation and sensitize receptors to painful stimuli.

it also promotes synthesis of prostacyclin, which causes vasodilation.

Question 5

describe the beneficial and adverse actions of NSAIDs and the basic mechanism.

Answer 5

NSAIDs help by alleviating mild to moderate pain, suppress fever, relieve dysmenorrhea
NSAIDs hurt by posing a risk of serious harm d/t stomach ulcers.

The basic mechanism for NSAIDs is to inhibit the COX. 1st generation inhibit COX 1 & COX 2 and second generation inhibit COX 2 only.

Question 6

explain how NSAIDs can lead to MI stroke. What is the main mechanism that promotes this risk?

Answer 6

due to their prothrombotic (blood clotting) properties, NSAIDs can lead to MI and stroke. The main mechanism that promotes this risk is the inhibition of the cyclooxygenase enzyme.

Question 7

discuss the role of COX in synthesizing prostaglandins that increase blood flow and how a COX inhibitor can thus cause renal impairment

Answer 7

COX 1 synthesizes prostaglandins to increase blood flow to the kidneys, which supports the renal system. If COX 1 is inhibited, renal impairment occurs because the renal tubes are not dilated enough.

Question 8

state the main difference between aspirin and other NSAIDs.

Answer 8

Aspirin’s effects are irreversible, whereas other NSAIDS are reversible.

Question 9

differentiate the first generation NSAIDs from the second generation NSAIDs.

Answer 9

first generation NSAIDS inhibit COX 1 and COX 2

second generation NSAIDS inhibit just COX 2v

Question 10

regarding the selective COX 2 inhibitor (celecoxib), describe the MOA, clinical use, and AEs.

Answer 10

MOA: Selective inhibition of COX-2, No inhibition of COX-1

clinical use: last choice for long term management of pain Osteoarthritis, Rheumatoid arthritis ,Acute pain
Dysmenorrhea, Familial adenomatous polyposis

AEs: Dyspepsia, Abdominal pain, Renal impairment, Sulfonamide allergy, Cardiovascular impact (stroke, MI, and other serious events)

Question 11

why can a COX 2 inhibitor increase incidence of MI?

Answer 11

This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2), which leads to vasoconstriction and thrombus

Question 12

list main drug interactions for aspirin, NSAIDs (ibuprophen, naproxen) and Tylenol

Answer 12

Tylenol:
Alcohol–regular alcohol use increases risk of liver injury (use less than 2,000 mg/day)
Warfarin
Vaccines

Question 13

list main drug interactions for aspirin

Answer 13

anticoagulants–intensify effects
glucocorticoids–ulcer risk higher
alcohol–gastric bleeding risk
non-aspirin NSAIDS–other NSAIDs can reduce the antiplatelet effects of aspirin
ACE inhibitors and ARBs–can impair renal function and increase risk of acute renal failure
vaccines–can blunt the immune response to vaccines

Question 14

list main drug interactions for ibuprofen

Answer 14

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Question 15

list main drug interactions for naproxen

Answer 15

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Question 16

considering acetaminophen, explain the MOA, beneficial and adverse effects

Answer 16

Selective inhibition of COX and limited to the CNS
Decreases prostaglandin synthesis in CNS so mainly treats fever/pain

beneficial effects: Analgesic, antipyretic
Does not have any anti-inflammatory or antirheumatic actions
Not associated with Reye’s syndrome, so safe with children
Does not increase platelet aggregation
Does not reduce blood flow to kidneys
No increase in GI ulcers

adverse effects: Very few at normal doses (use less than 4,000 mg/day)
Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and toxic epidermal necrolysis (TEN)
Hepatotoxicity
With overdose or in patients with liver failure
Overdose: Hepatic necrosis

Question 17

when is aspirin contraindicated?

Answer 17

in patients who have a known allergy to NSAIDs and also in pregnancy
alternative would be Tylenol

Question 18

compare signs and symptoms of acute poisoning with aspirin and with acute toxicity acetaminophen, the time course and management

Answer 18

Acetaminophen:
Overdose: Hepatic necrosis
Signs and symptoms of hepatic failure, coma, death
Early symptoms: Nausea and vomiting, diarrhea, sweating, abdominal pain
Treatment for overdose: Acetylcysteine (Mucomyst)

aspirin: acute poisoning
Immediate threats to life: Respiratory depression, hyperthermia, dehydration, and acidosis. Treatment is largely supportive.

Question 19

discuss the safety of NSAIDs with pts. who have chronic kidney disease

Answer 19

NO GIVING NSAIDs to pts. with chronic kidney disease because NSAIDs disrupt the compensatory vasodilation response of renal prostaglandins to vasoconstrictor hormones released by the body.

Inhibition of renal prostaglandins results in acute deterioration of renal function after ingestion of NSAIDs.

Question 20

recognize the 4 step approach for the use of COX inhibitors for musculoskeletal pain.

Answer 20

step one: non drug measures
step two: initiate with acetaminophen or aspirin
step three: try other non-selective NSAIDs-naproxen, ibuprofen, or a nonacetylated salicylate
step four: as a last resort: try the selective COX-2 inhibitor celecoxib

Question 21

summarize nursing implications and patient teaching for NSAIDs and acetaminophen

Answer 21

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