Chapter 17 Nonopioid Analgesics: NSAIDs, COX-2 Inhibitors, and Acetaminophen

Question 1

NSAIDs are structurally diverse, but all have

Answer 1

antipyretic, anti-inflammatory and analgesic or antihyperalgesic
properties

Question 2

How does acetaminophen differentiate from NSAIDs?

Answer 2

weak anti-inflammatory effects and its generally poor ability to inhibit cyclooxygenase (COX) in the presence of high concentrations of peroxides,
as are found at sites of inflammation.

Question 3

Unlike NSAIDs, acetaminophen does not have an adverse effects

Answer 3

on platelet function or gastric mucosa

Question 4

The mechanism of action of NSAIDs is

Answer 4

inhibition of prostaglandin
production from arachidonic acid by either reversible or irreversible acetylation of the cyclooxygenase
(COX)

Question 5

COX is present in at least two isoforms

Answer 5

(COX-1 and COX-2) and is dispersed throughout the

body.

Question 6

What is COX-1?

Answer 6

COX-1 isoform is constitutive, causing hemostasis, platelet aggregation, and the production of prostacyclin,
which is gastric mucosal protective. The inhibition
of the COX-1 isoform may be responsible for the adverse
effects related to the nonselective NSAIDs.

Question 7

COX-2 isoform that is induced by

Answer 7

proinflammatory stimuli
and cytokines causing fever, inflammation, and pain, and thus the target for antipyresis, anti-inflammation, and analgesia by NSAIDs

Question 8

COX-1 mediates the production of

Answer 8

prostaglandins that are essential in the homeostatic processes in the stomach (gastric protection), lung, and kidney, and platelet aggregation

Question 9

COX-2 is generally considered to be an inducible enzyme, provoking pathologic processes such as

Answer 9

fever, pain, and inflammation

Question 10

Where is COX-2 expressed?

Answer 10

COX-2, despite being the inducible isoform, is
expressed under normal conditions in a number of tissues, include brain, testis, and kidney.In inflammatory states, COX-2 becomes expressed in macrophages and other cells propagating the inflammatory process

Question 11

The pain associated with inflammation and prostaglandin

production results from

Answer 11

the production of prostanoids in the inflamed body tissues that sensitize nerve endings and leads to the sensation of pain

Question 12

NSAIDs peripheral

mechanisms of action.

Answer 12

Peripherally, prostaglandins
contribute to hyperalgesia by sensitizing nociceptive sensory
nerve endings to other mediators (such as histamine
and bradykinin) and by sensitizing nociceptors to respond to non-nociceptive stimuli (e.g., touch). Peripheral
inflammation induces a substantial increase in COX-2,
and prostaglandin synthase expression in the central nervous system (CNS)

Question 13

NSAIDs central

mechanisms of action.

Answer 13

Centrally, prostaglandins are recognized to have direct actions at the level of the spinal cord enhancing nociception, notably the terminals of sensory neurons in the dorsal horn

Question 14

Where in the spinal cord are COX-1 and COX-2 expressed ?

Answer 14

Both COX-1 and COX-2 are
expressed constitutively in dorsal root ganglia and spinal
dorsal and ventral gray matter but inhibition of COX-2 and
not COX-1 reduces hyperalgesia

Question 15

interleukin-1beta (IL-1b)

Answer 15

the proinflammatory cytokine interleukin-1beta (IL-1b) plays a
major role in inducing COX-2 in local inflammatory cells
by activating the transcription factor NF-kB

Question 16

In the CNS IL-1b causes

Answer 16

increased production of COX-2 and PGE2, producing hyperalgesia, but this is not the result of neural activity arising from the sensory fibers innervating the inflamed tissue or of systemic IL-1b in the plasma

Question 17

Interleukin 6 (IL-6)

Answer 17

interleukin 6 (IL-6) triggers the formation of PGE2 in the CNS, which in turn
causes increased production of COX-2 and PGE2.

Question 18

Two forms of input from peripheral inflamed tissue to the CNS.

Answer 18

The first is mediated by electrical activity in sensitized nerve fibers innervating the
inflamed area, which signals the location of the inflamed
tissue as well as the onset, duration, and nature of any
stimuli applied to this tissue. The second is a humoral signal
originating from the inflamed tissue, which acts to produce a widespread induction of COX-2 in the CNS

Question 19

FIGURE 17-1

Answer 19

Site of action of NSAIDs

Question 20

Administration of NSAIDs

Answer 20

NSAIDs are most often administered enterally, but intravenous,
intramuscular, rectal, and topical preparations are
available

Question 21

NSAIDs relation to protein

Answer 21

NSAIDs are highly bound to plasma proteins, specifically to albumin (.90%), and therefore only a small portion of the circulating drug in plasma exists in the unbound (pharmacologically active) form

Question 22

The volume of distribution of NSAIDs

Answer 22

is low, ranging from 0.1 to 0.3 L/kg, suggesting minimal tissue binding

Question 23

NSAIDs Acid or Base?

Answer 23

Most NSAIDs are weak acids with pKa less than 6, and since weak acids will be 99% ionized two pH units above their pKa, these antiinflammatory
medications are present in the body mostly in the ionized form. In contrast, the coxibs are nonacidic, which may play a role in the favorable tolerability profile

Question 24

Major absorptive site for orally administered NSAIDs

Answer 24

most NSAIDs are administered
enterally and their pH profile facilitates absorption via the
stomach, and the large surface area of the small intestine produces a major absorptive site for orally administered NSAIDs

Question 25

Most of the NSAIDs are rapidly and completely absorbed from the (GI) tract, with peak concentrations occurring within

Answer 25

1 to 4 hr. The presence of

food tends to delay absorption without affecting peak concentration

Question 26

NSAIDs available in parenteral forms in the United States

Answer 26

ketorolac, propacetamol,

and ibuprofen

Question 27

Topical NSAIDs possess the advantage

Answer 27

provide local action without systemic adverse effects. They are formulated to traverse the skin to reach the adjacent joints and muscles and exert therapeutic activity, and may offer some advantage in terms of decreased adverse event

Question 28

Types of Topical NSAIDs

Answer 28

These medications, such as diclofenac epolamine transdermal patch (Flector®) and diclofenac sodium gel (Voltaren®),

Question 29

The high protein binding of the NSAIDs has particular

relevance in

Answer 29

the state of hypoalbuminemia or decrease albumin concentrations (e.g., elderly, malnourished). A greater
fraction of unbound NSAIDs are present in the plasma,
which may enhance efficacy but also increase toxicity.

Question 30

Why does a possibility of

bleeding increased with concomitant use of NSAIDs?

Answer 30

NSAIDs compete for binding sites with other highly plasma

protein–bound drugs such as warfarin;

Question 31

The major metabolic pathway for elimination of NSAIDs

Answer 31

hepatic oxidation or conjugation. Renal excretion of
unmetabolized drug is a minor elimination pathway for most NSAIDs accounting for less than 10% of the administered
dose.

Question 32

most widely use analgesic,

antipyretic, and anti-inflammatory agent in the world

Answer 32

Acetylsalicylic acid (ASA)

Question 33

Aspirin is comprised of the active compounds

Answer 33

acetic acid and salicylic acid, forming acetylsalicylic acid.

Question 34

Aspirin inhibits the biosynthesis of prostaglandins by

Answer 34

means of an irreversible acetylation and consequent inactivation of COX; thus, aspirin inactivates COX permanently

Question 35

Naproxen Pharmacodynamics

Answer 35

absorbed after enteral administration and has a half-life of 14 hr. Peak concentrations in plasma occur within 4 to 6 hr. The half-life is approximately 14 hr, but steady-state serum levels require more than 48 hr. Naproxen has a volume of distribution of 0.16 L/kg

Question 36

Naproxen relation to protein

Answer 36

At therapeutic levels, naproxen is more than 99% albumin-bound.

Question 37

Naproxen Metabolism and Elimination

Answer 37

Naproxen is extensively metabolized to 6-0-desmethyl
naproxen, and both parent and metabolites do not induce
metabolizing enzymes. Most of the drug is excreted in
the urine, primarily as unchanged naproxen. About 30% of them drug undergoes 6-demethylation, and most of this metabolite, as well as naproxen itself, is excreted as
glucuronide or other conjugates.

Question 38

Naproxen indications

Answer 38

Naproxen has been used for the treatment of arthritis and other inflammatory diseases.

Question 39

Ibuprofen indications

Answer 39

use for the relief of symptoms of acute pain, fever, and inflammation. demonstrated in the treatment of headache and migraine, menstrual pain, and acute postoperative pain.

Question 40

Ibuprofen Pharmacodynamics

Answer 40

Ibuprofen is rapidly absorbed from the upper GI tract, with peak plasma levels achieved about 1 to 2 hr after administration. It is highly bound to plasma proteins
with an estimated volume of distribution of 0.14 L/kg,
and is primarily hepatically metabolized (90%) with less
than 10% excreted unchanged in the urine and bile. A
short plasma half-life (2 6 0.5 hr) a

Question 41

Ibuprofen dosage

Answer 41

usual starting dose: 50 or 75 mg with immediate release capsules every 6 to 8 hr or 200 mg with extended release capsules once daily. The maximum dose is 300 mg daily of immediate-release capsules or 200 mg
daily of extended-release capsules. Ibuprofen at a dose of 1200 to 2400 mg/day has a predominantly analgesic effect for mild to moderate pain
conditions, with dosage of 3200 mg/day recommended
only under continued care of clinical professionals

Question 42

Adverse Effect of Ibuprofen

Answer 42

at anti-inflammatory doses of more than 1600 mg per day,
renal side effects are almost exclusively encountered in
patients with low intravascular volume and low cardiac
output, particularly in the elderly.

Question 43

Ketoprofen administration

Answer 43

capsules release the drug in the stomach, whereas capsule
pellets (extended release) are designed to resist dissolution
in the low pH of gastric fluid, but release the drug at a
controlled rate in the higher pH environment of the small
intestine

Question 44

Ketoprofen Phamarcodynamics

Answer 44

Peak plasma levels are achieved about 1 to 2 hr

after oral administration for the capsules and the 6 to 7 hr after administration of the capsule pellets

Question 45

Ketoprofen relationship to protein

Answer 45

Ketoprofen has
high plasma protein binding (98%–99%) and an estimated
volume of distribution of 0.11 L/kg.

Question 46

Ketoprofen Metabolism

Answer 46

Ketoprofen is conjugated
with glucuronic acid in the liver, and the conjugate is excreted in the urine. The glucuronic acid moiety can be converted back to the parent compound. Thus, the metabolite serves as a potential reservoir for the parent drug, and this may be important in persons with renal
insufficiency

Question 47

Oxaprozin Pharmacodynamics

Answer 47

oxaprozin peak plasma levels are not achieved until 3 to 6 hr
after an oral dose, and its half-life of 40 to 60 hr allows for
once-daily administration.36 Peak plasma concentration
occurs at about 1.5 hr after administration

Question 48

Oxaprozin relationship to protein

Answer 48

Oxaprozin is highly bound to plasma proteins and has an estimated volume of distribution of 0.15 L/kg.

Question 49

Oxaprozin Metabolism

Answer 49

Oxaprozin is primarily

metabolized by the liver, and 65% of the dose is excreted into the urine and 35% in the feces as metabolites

Question 50

Oxaprozin Mechanism of Action

Answer 50

Oxaprozin diffuses readily into inflamed synovial tissues after oral administration and is capable of inhibiting both anandamide hydrolase in neurons and NF-kB activation in inflammatory cells, which are crucial for synthesis of proinflammatory and histotoxic mediators in
inflamed joints

Question 51

Diclofenac Mechanism of Action

Answer 51

Diclofenac has COX-2 selectivity and the selective inhibitor of COX-2 lumiracoxib is an analog of diclofenac.

Question 52

Diclofenac Bioavaliability

Answer 52

Diclofenac is rapidly absorbed
after oral administration, but in substantial first-pass
metabolism only about 50% of diclofenac is available systemically.
After oral administration, peak serum concentrations
are attained within 2 to 3 hr

Question 53

Diclofenac relationship to protein

Answer 53

Diclofenac is highly
bound to plasma proteins and has an estimated volume of
distribution of 0.12 L/kg.

Question 54

Diclofenac Excretion

Answer 54

Diclofenac is excreted primarily in the urine (65%), and as bile conjugates (35%).

Question 55

Diclofenac Formulations

Answer 55

Diclofenac is available in two enteral formulations, diclofenac sodium and diclofenac potassium. Diclofenac potassium is formulated to be released and absorbed in the stomach. Diclofenac sodium, usually distributed in enteric-coated tablets, resists
dissolution in low pH gastric environments, releasing
instead in the duodenum

Question 56

Diclofenac Adverse Effects

Answer 56

Hepatotoxicity via elevated
transaminases may occur, and transaminases should be
measured during therapy with diclofenac.

Question 57

What happens to Diclofenac after after oral administration?

Answer 57

Uniquely, diclofenac
accumulates in synovial fluid after oral administration,
which may explain why its duration of therapeutic effect
is considerably longer than the plasma half-life of 1 to
2 hr.

Question 58

The transdermal application of diclofenac has shown efficacy in the treatment of

Answer 58

musculoskeletal disorders

such as ankle sprains, epicondylitis, and knee osteoarthritis

Question 59

The advantage of the transdermal formulation is

Answer 59

the lack of appreciable systemic absorption (6% [158 times lower] of the systemic exposure from enteral diclofenac sodium), and accumulation of the medication at the site of
application, thereby providing local pain relief. In comparison
to enteral delivery, topical application of diclofenac
provides analgesia by peripheral activity and not central mediation

Question 60

Etodolac

Answer 60

Etodolac has some degree of COX-2 selectivity

Question 61

Etodolac Pharmacodynamic

Answer 61

The analgesic effect of full doseslasting up to 8 hr. After oral administration,
peak serum concentrations of 16 and 25 mg/L are attained within 2 hr of administering 200 and 400 mg,
respectively

Question 62

Etodolac and Plasma Protein

Answer 62

Etodolac is highly bound to plasma proteins

and has an estimated volume of distribution of 0.4 L/kg.

Question 63

Etodolac Excretion

Answer 63

Etodolac is excreted primarily in the urine, and 60% of a
dose is recovered within 24 hr. More than 60% of the
metabolites are hydroxylated with glucuronic conjugation.

Question 64

Etodolac Dosage

Answer 64

Usual 24-Hr Adult Dose Range: 400–1200 mg
Adult Daily Dose and
Frequency200–300 mg BID, TID, QID

Question 65

Indomethacin mechanism of action

Answer 65

This is a nonselective COX inhibitor

Question 66

Indomethacin pharmacodynamics

Answer 66

Peak concentrations
occur 1 to 2 hr after dosing. Indomethacin is 90%
bound to plasma proteins and tissues

Question 67

Indomethacin CSF, Synovial, and Plasma concentration

Answer 67

The concentration of the drug in the cerebrospinal fluid is low, but its concentration
in synovial fluid is equal to that in plasma within 5 hr of administration

Question 68

Indomethacin Adverse Effects

Answer 68

GI irritation are common, including diarrhea, and
ulcerative lesions are a contraindication to indomethacin
use

Question 69

Intravenous indomethacin

Answer 69

has FDA approval for
closure of persistent patent ductus arteriosus but its side
effect profile limits other uses

Question 70

Ketorolac

Answer 70

Ketorolac tromethamine is a NSAID with activity at
COX-1 and COX-2 enzymes, which block prostaglandin
production

Question 71

Ketorolac Peak

Answer 71

After oral administration, peak serum concentrations

are attained within 1 to 2 hr.

Question 72

Ketorolac and Protrein

Answer 72

Ketorolac is highly bound to plasma proteins and has an estimated volume of distribution of 0.28 L/kg.

Question 73

Ketorolac Excretion

Answer 73

Ketorolac is excreted primarily in the urine and has a half-life of
approximately 5 to 6 hr in healthy subjects.

Question 74

Ketorolac Formulations

Answer 74

Administration of ketorolac is available for enteral, ophthalmic, and parenteral delivery, and is only one of two parenteral NSAIDs
currently available

Question 75

Ketorolac Indications

Answer 75

Ketorolac has been used to treat mild to severe
pain following major surgical procedures, including general
abdominal surgery, gynecologic surgery, orthopedic
surgery, and dentistry

Question 76

Ketorolac compared to Morphine

Answer 76

When compared to morphine,
ketorolac 30 mg intramuscular (IM) has been
shown to be equivalent to 12 mg morphine IM and 100 mg
meperidine IM

Question 77

Ketorolac Adverse Effects

Answer 77

may precipitate or exacerbate
renal failure in hypovolemic elderly patients and
especially those with underlying renal dysfunction.
Therefore, ketorolac is recommended for limited use
(3–5 days)

Question 78

Nabumetone

Answer 78

Nabumetone is a prodrug that undergoes hepatic biotransformation
to the active component, 6-methoxy-2-
naphthylacetic acid (6MNA), which has some degree of
COX-2 selectivity conferring less gastric irritation compared
with other NSAIDs

Question 79

Nabumetone and Protein

Answer 79

Nabumetone is highly bound
to plasma proteins and has an estimated volume of distribution
of 0.68 L/kg.

Question 80

Nabumetone Excretion

Answer 80

Nabumetone is excreted primarily in
the urine and has a half-life of approximately 20 to 24 hr
in healthy subjects, thereby enabling single daily dosing.

Question 81

Nabumetone Indications

Answer 81

When compared with other NSAIDs, nabumetone has
tended to show efficacy54 and tolerability in the treatment
of arthritis

Question 82

Mefenamic Acid

Answer 82

Mefenamic acid blocks prostaglandin synthesis but also the tissue response to prostaglandins

Question 83

Mefenamic Acid peak serum concentration

Answer 83

Peak serum concentrations are attained within 2 to 4 hr and the half-life is 3 to 4 hr

Question 84

Mefenamic Acid and protein

Answer 84

Mefenamic acid is highly bound to plasma

proteins and is excreted primarily in the urine

Question 85

Mefenamic Adverse Effects

Answer 85

Mefenamic acid has been associated with severe pancytopenia and many other side effects. Hence, therapy is not to occur for
more than 1 week

Question 86

Meloxicam MAO

Answer 86

The enolic acid derivative shows nonselectivity, except for meloxicam which shows relative COX-2 selectivity

Question 87

Meloxicam Dosage

Answer 87

7.5 mg is more selective for COX-2 and at 15 mg

meloxicam becomes less selective

Question 88

Meloxicam Peak Serum, Protein, Half-life

Answer 88

After oral administration,
peak serum concentrations are attained within 5 to
10 hr after administration. Meloxicam is highly bound to plasma proteins and has an estimated half-life of approximately 15 to 20 hr in healthy subject

Question 89

COX-2 inhibitors

Answer 89

celecoxib, rofecoxib, and valdecoxib)

Question 90

What does all of the coxibs have in common?

Answer 90

They all achieve sufficient brain concentrations to have a central analgesic effect, and all reduce prostaglandin
formation in inflamed joints

Question 91

the relative degree of selectivity for

COX-2 inhibition is

Answer 91

lumiracoxib= etoricoxib > valdecoxib = rofecoxib&raquo_space;celecoxib

Question 92

Celecoxib

Answer 92

After oral administration,
peak serum concentrations are attained 2 to 3 hr
after administration

Question 93

Celecoxib : Plasma protein, metabolism, half-life

Answer 93

Celecoxib is highly bound to plasma proteins, is excreted primarily by hepatic metabolism, and has a half-life of approximately 11 hr in healthy subjects

Question 94

Does Celecoxib have increased risk of bleeding?

Answer 94

Celecoxib does not interfere with platelet aggregation;
thus, perioperative administration can be conducted as part of a multimodal analgesic regimen without increased
risk of bleeding

Question 95

Celecoxib Adverse Effect

Answer 95

NSAID-induced GI complications are one of the most common drug related
serious adverse events, but celecoxib preferentially
inhibits the inducible COX-2 isoform and not the
constitutive COX-1 isoform, thus conferring some gastroprotective effect

Question 96

Etoricoxib Mechanism of Action

Answer 96

Etoricoxib is a second-generation, highly selective (COX-2) inhibitor with anti-inflammatory and analgesic properties. It shows dose-dependent inhibition
of COX-2 across the therapeutic dose range,
without inhibition of COX-1

Question 97

Etoricoxib effect on prostaglandin synthesis and platelet function

Answer 97

does not inhibit gastric
prostaglandin synthesis; and has no effect on platelet
function.

Question 98

Acetaminophen (paracetamol [APAP])

Answer 98

an analgesic and antipyretic medication that produces its analgesic effect by inhibiting central prostaglandin synthesis with minimal inhibition of peripheral prostaglandin synthesis

Question 99

Acetaminophen:
Peak Serum Concentration, Plasma proteins,
Volume of Distribution
Half-life

Answer 99

After oral administration, peak serum concentrations are attained within 0.5 to 3 hr. A small portion of acetaminophen is bound to plasma proteins (10%–50%) and has an estimated
volume of distribution of 0.95 L/kg. The half-life of is ~ 2 to 3 hr in healthy pts

Question 100

Acetaminophen Elimination

Answer 100

Acetaminophen is

eliminated from the body primarily by formation of glucuronide and sulfate conjugates in a dose-dependent manner

Question 101

Acetaminophen and NSAIDs Differences

Answer 101

acetaminophen’s weak anti-inflammatory effects and its generally poor ability to inhibit COX in the presence of high concentrations of peroxides as are found at sites of inflammation

Question 102

Acetaminophen effect on platelet function or the gastric mucosa

Answer 102

Does not have an adverse effect on platelet function or the gastric mucosa.

Question 103

Acetaminophen Metabolism

Answer 103

It is absorbed rapidly, with peak plasma levels seen within 30 min to 1 hr, and is metabolized in the liver by conjugation and hydroxylation to inactive metabolites, with a duration of action of 4 to 6 hr.

Question 104

The American Geriatrics Society advocates the dose of Acetaminophen

Answer 104

4 g as the total daily dose in elderly persons, with the exceptions of patients with hepatic insufficiency or
history of alcohol abuse for whom a maximum dose reduction of 50% to 75% is recommended

Question 105

A useful method of assessing the efficacy of medications,

Answer 105

the “number needed to treat” (NNT), evaluates the efficacy of active treatment compared to placebo

Question 106

number needed to treat” (NNT)

Answer 106

measures how many patients need to receive a certain treatment in order for one patient to derive a clear benefit. In pain studies, this translates into
the number of patients needed to treat with a certain drug in order for one patient to achieve at least a 50% decrease in pain intensity

Question 107

Number Needed to Treat calculations

Answer 107

This value is calculated by 1/([goal achieved active group/total active] – [goal achieved placebo
group/total placebo]); the 95% confidence interval
(CI) of NNT can be obtained by taking the reciprocal
value of the 95% CI for absolute risk reduction

Question 108

NSAIDs adverse effects

Answer 108

GI ulceration and bleeding, disturbance of platelet function, sodium and water retention, nephrotoxicity, and hypersensitivity reactions

Question 109

The three most common adverse drug reactions to NSAIDs are

Answer 109

GI, dermatologic, and

neuropsychiatric

Question 110

risk factors for the

development of NSAID-induced gastropathy

Answer 110

history of GI complications, high-dose or multiple

NSAIDs, advanced age, concomitant corticosteroid use, and alcohol use

Question 111

GI-protective agents that attenuate the complications associated with long-term NSAID use

Answer 111

misoprostol, H2-receptor antagonist, and proton
pump inhibitors).Other strategies: selective COX-2 inhibitors such as celecoxib,
which are less ulcerogenic in the GI tract as compared
with nonselective NSAID

Question 112

NSAIDs causes decrease renal function and renal failure by

Answer 112

The proposed mechanism is reduction in prostaglandin production leading to increased reduced renal
blood flow with subsequent medullary ischemia may result from NSAID use in susceptible individuals

Question 113

The risk factors for NSAID-induced renal toxicity

Answer 113

chronic NSAID use, high-dose or multiple NSAIDs, volume depletion, congestive heart failure, vascular disease, hyperreninemia, shock, sepsis, systemic lupus
erythematous, hepatic disease, sodium depletion, nephrotic syndrome, diuresis, concomitant drug therapy (diuretics, ACE inhibitors, beta blockers, potassium supplements), and advanced age

Question 114

The mechanism by which almost all NSAIDs

produce hepatoxicity

Answer 114

immunologic or metabolic, with dose-related toxicity being seen in aspirin and acetaminophen

Question 115

Acetaminophen Metabolism

Answer 115

Acetaminophen is almost entirely metabolized in

the liver, and the minor metabolites are responsible for the hepatotoxicity seen in overdoses

Question 116

Mechanisms of acetaminophen hepatotoxicity include

Answer 116

depletion of hepatocyte

glutathione, accumulation of the toxic metabolite NAPQI, mitochondrial dysfunction, and alteration of innate immunity

Question 117

Acetaminophen Hepatotoxicity Risk factors

Answer 117

include concomitant depression, chronic pain, alcohol or narcotic use, and/or using several
preparations simultaneously

Question 118

The lowest dose of acetaminophen to cause hepatotoxicity

Answer 118

between 125 and 150 mg/kg.90,91 The threshold dose to cause hepatotoxicity is 10 to 15 g of acetaminophen for adults and 150 mg/kg for children. The most recognized dosing
limit is 4 g/24 hr in healthy adult patients

Question 119

Thromboxane A2 (TXA2)

Answer 119

Thromboxane functions
as a vasoconstrictor, and facilitates platelet aggregation. Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of
new platelets as well as increasing platelet aggregation

Question 120

Inhibition of cyclooxygenase reduces the production of

Answer 120

thromboxane and prostacyclin

Question 121

Endothelial-derived prostacyclin (PGI2)

Answer 121

functions in concert with thromboxane, primarily inhibiting platelet activation,
thus preventing the formation of hemostatic plug

Question 122

COX inhibition on thromboxane and prostacyclin production

Answer 122

Nonselective NSAIDs inhibit both the COX-1 and
COX-2, thereby reducing production of thromboxane
and prostacyclin. The imbalance of thromboxane and prostacyclin may lead to a thrombogenic situation

Question 123

Aspirin effect on Platelets

Answer 123

Low-dose aspirin (81 mg/day)
is a platelet aggregation inhibitor, thereby reducing thrombotic events related to platelet aggregation. Aspirin at larger doses 1.5 to 2 g/day has been described to result in a paradoxical thrombogenic effect.

Question 124

Celecoxib effect on platelet

Answer 124

Celecoxib is an antiinflammatory agent that primarily inhibits COX-2, an inducible enzyme not expressed in platelets, and thus does not interfere with platelet aggregation