Ch 71 NSAIDs and acetaminophen

Question 1

All of the drugs discussed in this chapter inhibit __.

Answer 1

cyclooxygenase (COX),

an enzyme that converts arachidonic acid into prostanoids (prostaglandins and related compounds).

Question 2

Cyclooxygenase has two forms:

Answer 2

COX-1 and COX-2.

Question 3

The cyclooxygenase inhibitors fall into two major groups:

Answer 3

nonsteroidal anti-inflammatory drugs (NSAIDs) and

acetaminophen (in a group by itself).

Question 4

The NSAIDs can be subdivided into two groups:

Answer 4

(1) firstgeneration NSAIDs, which inhibit COX-1 and COX-2, and
(2) second-generation NSAIDs, which selectively inhibit COX-2.

Question 5

Inhibition of COX-1 can cause (3).

Answer 5

gastric ulceration, renal impairment, and bleeding

Question 6

Inhibition of COX-2 suppresses __.

Answer 6

inflammation, pain, and fever, but can also cause renal impairment

Question 7

__ is the prototype of the first-generation NSAIDs.

Answer 7

Aspirin

Question 8

Aspirin has four major beneficial actions:

Answer 8

suppression of inflammation,
relief of mild to moderate pain,
reduction of fever, and
prevention of MI and stroke (secondary to suppressing platelet aggregation).

All of these benefits result from inhibiting COX-2, except for prevention of MI and stroke, which results from inhibiting COX-1 (in platelets).

Question 9

Because aspirin inhibits COX-1 as well as COX-2, it cannot cause beneficial effects without posing a risk of (3).

Answer 9

gastric ulceration, bleeding, and renal impairment.

Question 10

__ causes irreversible inhibition of cyclooxygenase.

Answer 10

Aspirin

As a result, the effects of aspirin persist until cells can
make more cyclooxygenase.

Question 11

Because platelets are unable to synthesize new cyclooxygenase, the antiplatelet effects of a single dose of aspirin __.

Answer 11

persist for the life of the platelet (about 8 days).

Question 12

__ of aspirin are much higher than analgesic or antipyretic doses.

Answer 12

Anti-inflammatory doses

Question 13

__ is a useful drug for rheumatoid arthritis and other chronic inflammatory conditions.

Answer 13

Aspirin

Question 14

Aspirin is a very effective __.

Answer 14

analgesic.

It can be as effective as opioids for some types of postoperative pain.

Question 15

The risk of aspirin-induced gastric ulcers can be reduced

by:

Answer 15

(1) testing for and eliminating H. pylori before starting
therapy and by
(2) giving a proton pump inhibitor or histamine2 receptor antagonist.

Question 16

Because of its antiplatelet actions, aspirin can protect against __.

Answer 16

MI, stroke, and other thrombotic events

Question 17

When taken for primary prevention, the benefits of aspirin
must be weighed against the potential for harm. Ibuprofen, naproxen, and other nonaspirin NSAIDs can antagonize the antiplatelet actions of aspirin and can thereby __.

Answer 17

decrease protection against MI and stroke.

To minimize this interaction, patients should take aspirin about 2 hours before other NSAIDs.

Question 18

Because of its antiplatelet actions, high-dose aspirin should be discontinued __.

Answer 18

1 week before elective surgery or parturition.

In most cases, low-dose aspirin taken to protect against thrombosis can be continued.

Question 19

Because of its antiplatelet actions, aspirin can increase the risk of bleeding in patients taking __.

Answer 19

warfarin, heparin, and other anticoagulants.

Question 20

By impairing renal function, aspirin can cause (3).

Answer 20

sodium and water retention, edema, and elevation of blood pressure.

However, adverse outcomes are likely only in patients
with additional risk factors: advanced age, pre-existing
renal dysfunction, hypovolemia, hypertension, hepatic
cirrhosis, or heart failure.
Long-term aspirin use may lead to renal papillary necrosis and other forms of renal injury.

Question 21

Because of the risk of Reye’s syndrome, aspirin should

be avoided by __.

Answer 21

children with influenza or chickenpox

Question 22

Use of aspirin during labor and delivery can (3).

Answer 22

suppress spontaneous uterine contractions,
induce premature closure of the ductus arteriosus,
and intensify uterine bleeding.

Question 23

Although rarely fatal in adults, aspirin poisoning may prove __.

Answer 23

lethal in children

Question 24

Aspirin can cause hypersensitivity reactions, especially in __.

Answer 24

adults with asthma, rhinitis, and nasal polyps.

Severe reactions (anaphylaxis) can be treated with epinephrine.

Question 25

All of the nonaspirin first-generation NSAIDs are much
like aspirin itself. All of these drugs inhibit COX-1 and
COX-2; they all:

Answer 25

can suppress inflammation, pain, and fever;

and they all can cause gastric ulceration, renal impairment, and bleeding.

Question 26

The nonaspirin NSAIDs differ from aspirin in three important ways.

Answer 26

First, nonaspirin NSAIDs cause reversible inhibition of COX, and hence their effects decline as soon as their blood levels decline.

Second, although they can suppress platelet aggregation, these drugs are not used to prevent MI and stroke.

Third, these drugs actually increase the risk of MI and stroke, and hence should be used in the lowest effective dosage for the shortest possible time.

Question 27

By inhibiting COX-2, the second-generation NSAIDs

(coxibs) can suppress __.

Answer 27

inflammation, pain, and fever

Question 28

By sparing COX-1, the coxibs may cause __.

Answer 28

less gastric ulceration than the first-generation NSAIDs.

Question 29

Coxibs do not inhibit __.

Answer 29

platelet aggregation, and hence do not pose a risk of bleeding.

Question 30

Like all first-generation NSAIDs (except aspirin), coxibs

pose a risk of __.

Answer 30

MI and stroke

Question 31

Currently, __ is the only coxib on the market.

Answer 31

celecoxib [Celebrex]

Question 32

__ reduces pain and fever, but not inflammation.

Answer 32

Acetaminophen

Question 33

Acetaminophen inhibits prostaglandin synthesis in the CNS, but not in the periphery. As a result, acetaminophen differs from the NSAIDs in four ways:

Answer 33

it (1) lacks anti-inflammatory actions,

(2) does not cause gastric ulceration,
(3) does not suppress platelet aggregation, and
(4) does not impair renal function.

Question 34

__ from acetaminophen overdose results from the accumulation of a toxic metabolite.

Answer 34

Hepatic necrosis

Risk is increased by undernourishment, alcohol consumption, and pre-existing liver disease.

Question 35

__ increases the risk of liver damage from acetaminophen overdose, but probably not from therapeutic doses.

Answer 35

Chronic alcohol consumption

Two major mechanisms are involved: induction of cytochrome P450 (which increases production of the toxic metabolite of acetaminophen) and depletion of glutathione stores (which reduces detoxification of the metabolite).

Question 36

Acetaminophen may increase the risk of __.

Answer 36

warfarin-induced bleeding by inhibiting the metabolism of warfarin

Question 37

__ is associated with SJS, AGEP, and TEN.

Answer 37

Acetaminophen

If rash appears, this may be a medical emergency.

Question 38

Acetaminophen overdose is treated with __.

Answer 38

PO or IV acetylcysteine,

a drug that substitutes for depleted glutathione in the reaction that clears the toxic metabolite of acetaminophen.