Download Anti-inflammatory Medications

Chapter 3
Anti-inflammatory
Medications
1
NSAIDs
 The use of NSAIDs for the treatment of
sports-related injuries, as well as other
maladies, (namely osteoarthritis)
continues to rise.
 In 2001, sales of NSAID prescriptions
accounted for $10.9 billion in the United
States.
2
NSAIDs (cont.)
 A thorough understanding of drug
actions, interactions, and effects allows
the athletic trainer to educate athletes on
treatment plans and symptoms resulting
from NSAIDs
3
NSAIDs (cont.)
 A recent study of high school football
players revealed that 75% of those
surveyed had used NSAIDs in the
previous 3 months and 15% of the
respondents were daily NSAID users.
The daily users often used the drugs
prophylactically prior to practices and
games.
4
The Inflammatory
Response
 The acute inflammatory cascade is set
into motion by the initial tissue insult.
 Grossly, acute inflammation is recognized
by the classic and familiar signs of pain
(dolor), heat (calor), erythema (rubor),
swelling (tumor), and loss of function
(functio laesa).
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Figure 3-1: The
Inflammatory Response
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Inflammatory Response
(cont.)
 Following a short period of
vasoconstriction - cellular injury signals
the release of chemical mediators, such
as histamine, serotonin, anaphylatoxins,
bradykinin, thromboxane, leukotrienes,
and prostaglandins.
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Box 3-2 page 36
 Major actions of the Eicosanoids
 Prostaglandins
 Thromboxane
 Leukotrienes
8
Anti-inflammatory
Medications
 Aspirin (acetylsalicylic acid) - a derivative
of salicylic acid.
 Salicylic acid, in turn, was created from
salicin, which is found in the bark of willow
trees.
 Aspirin was first synthesized by a Bayer
Company chemist in the late 19th century.
 It proved to be far less of a gastric irritant
than salicylic acid and was introduced to the
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marketplace in the spring of 1899.
 In 1971, Sir John Vane discovered that the
aspirin molecule transfers a functional
group onto the cyclooxygenase enzyme.
Until this time the actual mechanism of
action for aspirin was unknown.
10
Cyclooxygenase Enzyme
(COX)
 This enzyme is irreversibly inhibited and
unable to bind arachidonic acid, therefore,
the enzyme can no longer convert
arachidonic acid to prostaglandins and
thromboxane.
 The Leukotriene pathway, however, is
unaffected
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Effects of Aspirin




Analgesic
Antipyretic
Anticoagulant
Anti-inflammatory
12
Effects of Aspirin
 3000 – 6000 mg per day for antiinflammatory action; a series of chemical
events results from the blockage of
cyclooxygenase
 325 mg aspirin = 12 to 18 aspirin per day
to reach an anti-inflammatory effect
13
Effects of Aspirin
 The decrease in prostaglandin production
leads to a corresponding reduction in
inflammation and edema.
14
Effects of Aspirin
 Blocks prostaglandin production, even
the “cytoprotection.”
 In the GI tract, aspirin can cause gastric
upset, bleeding, and even ulcers.
 Various studies have shown GI disturbance
incidence of anywhere from 2 percent to 40
percent.
15
Effects of Aspirin
 The mechanism of gastric irritation
appears related to the direct effect of
aspirin upon the lining of the stomach.
 Mild gastrointestinal upset can often be
avoided if aspirin is taken with a meal,
due to the "buffering" action of the food.
16
Effects of Aspirin
 Aspirin use may also result in
complications, such as prolonged
bleeding and tinnitus.
 Decreased platelet function lasts from 4 to 6
days (used for blood thinning in heart
patients).
 Tinnitus may be an indication of aspirin
toxicity.
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Reye’s Syndrome
 Reye’s syndrome is a rare and potentially
devastating, acute illness that usually
strikes children following a viral infection
when they are given aspirin to lower
fever.
 This syndrome is now suspected in teens
and young adults with viral infections who
take aspirin.
18
Table 3-1: The Five
Clinical Stages of Reye’s
Syndrome
19
Aspirin Sensitive Asthma
 Upon exposure to even small quantities
of aspirin, those affected may develop
nasal congestion and acute, often severe
bronchospasm.
 There is an almost universal crossreactivity with other NSAIDs.
 Patients can be desensitized over time
with daily administration of aspirin and
cross-tolerance to other NSAIDs usually
occurs.
20
Acetaminophen
 Acetaminophen (Tylenol) is not an antiinflammatory agent, it has antipyretic and
analgesic properties.
 Will be discussed with the analgesics
(Chapter 10).
21
NSAIDs
 COX-2 Inhibitors
 Primarily induced at sites of inflammation
 COX-2 inhibitor could block the production of
proinflammatory prostaglandins without
interfering with gastric protection or platelet
activity
 Research is controversial and the drugs are
expensive
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Overview of Selected
NSAIDs
 Box 3-4 Page 42 – Factors to Consider in
Choosing an NSAID

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Age of Patient
Duration of Treatment
Time of Onset
Compliance
Other Medications
General Health of Patient
Cost of Treatment
23
Ibuprofen
 Advil, Motrin, Nuprin
 Most frequently used NSAID
 Introduced to the OTC market in 1985, it
is available in 200 to 800 mg tablets by
prescription, and 200 mg tablets OTC
 Frequently used as an antipyretic in
adults and children, as its longer duration
of action makes it a popular alternative to
acetaminophen
24
Ibuprofen
 Peak plasma levels are achieved within
15 to 30 minutes of ingestion
 Rapid onset of action can be quite
beneficial for quick relief of pain
 Half-life of about 2 hours, it must be
taken every 6 to 8 hours to maintain
effect
 An anti-inflammatory regimen requires
2400 – 3200 mg daily
25
Ibuprofen
 Taken in three separate doses, allowing it
to be taken at meal times, lessening the
likelihood of gastric irritation.
 Sufficient analgesia should be achieved
by daily dosages of less than 2400 mg
per day.
 Approximately 10 percent to 15 percent
of individuals must discontinue use
secondary to gastrointestinal symptoms.
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Naproxen
 Naprosyn, Aleve.
 Chemically similar to ibuprofen.
 Naproxen is available as the OTC preparation
Aleve, and as Anaprox by prescription.
 Due to naproxen's long half-life (approximately
12 hours), the daily recommended dosage of
750 – 1000 mg can be taken on a twice daily
schedule, reducing gastric upset due to only
two exposures and improving compliance.
27
Naproxen
 Peak plasma levels are achieved within 2
to 4 hours
 Incidence of upper gastrointestinal
bleeding in OTC use is double that of
OTC ibuprofen
28
Indomethacin
 Indocin.
 Although particularly effective in maladies
such as rheumatoid arthritis, ankylosing
spondylitis, and gout, indomethacin is
typically not recommended for use as a
simple analgesic or antipyretic due to
potentially severe side-effects.
 Up to half of those using indomethacin
may experience some side-effects and
almost one-third will discontinue use.
29
Indomethacin
 Common side-effects include
gastrointestinal symptoms (ulceration,
nausea, abdominal pain) and headaches
(15 percent to 25 percent of patients).
 Peak concentrations can be achieved in 1
to 2 hours (in fasting subjects, onset is
delayed by food intake).
30
Indomethacin
 A half-life of about 2.5 hours.
 Daily dosage ranges from 75 mg – 100
mg taken in two to three doses.
 Indomethacin’s use has declined as newer
agents with a lower side-effect profile have
emerged.
31
Nabumetone (Relafen)
 Only nonacid NSAID currently available
 Once-a-day treatment; half-life is 24
hours
32
Rofecoxib
 Vioxx
 One of only three potent and highly
selective COX-2 inhibitors available.
 It does not inhibit COX-1 and has no
effect on platelet function.
 It is FDA approved for the treatment of
osteoarthritis, dysmenorrhea, and acute
pain.
33
Rofecoxib
 Dosages range from 12.5 mg – 50 mg. It
is administered once daily given its
nearly 17-hour half-life.
 Long-term toxic effects, including
gastrointestinal and renal effects, are not
yet known given the drug’s relatively
recent introduction.
34
Celecoxib
 Celebrex
 COX-2 inhibitor
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
200 mg tablets
Peak Plasma levels = 3 hours
Half-life (approximate-effective) = 11 hours
Problems include:
 Liver and kidneys
 Heart ?
35
Ketorolac
 Toradol.
 Not typically employed for its antiinflammatory properties.
 It is the only NSAID available for
intramuscular or intravenous injection as
well as oral administration.
36
Ketorolac
 Although it also has anti-inflammatory
and antipyretic properties, it is most
commonly marketed and used as an
analgesic, particularly in postoperative
patients.
 As an analgesic, ketorolac offers great
promise as it avoids the most common
shortcomings of opioids, i.e., tolerance,
withdrawal effects, and respiratory
depression.
37
Ketorolac
 Interestingly, Tokish et al (1992) recently
reported that 28 of 30 National Football
League team medical staffs commonly
use ketorolac intramuscular injections on
game days for pain relief.
 Due to high risk of renal effects, duration
of ketorolac treatment is typically held to
less than 5 days.
38
NSAID Indications
39
NSAID Adverse Effects
40
NSAID Use
41
Drug-Drug Interactions
42
Glucocorticosteroids
 Animal studies demonstrate:
 Potent anti-inflammatory actions of
glucocorticosteroids and their subsequent
effects upon healing
 Glucocorticosteroids induced an early,
transient recovery of the force-generating
capacity of the effected muscle
 Long-term findings revealed irreversible
damage to the healing muscle, including
atrophy and diminished force-generating
capacity
43
Actions of Corticosteroids
44
Corticosteroids in Sports
Medicine
 Stanley and Weaver (1989) state that
“inconsistency in the studies on
glucocorticosteroid use does not lend
adequate support or direction to the
sports medicine clinician in their use.”
 Extremely powerful anti-inflammatory
medications but no good research to
demonstrate their effectiveness in
activity-related injury.
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Box 3-7: Most Common
Indications for Injectable
Corticosteroids
46
Box 3-8: Potential
Complications of
Injectable Corticosteroids
47