Anti-inflammatory Medications
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Transcript 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
11
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.
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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
22
Overview of Selected
NSAIDs
Box 3-4 Page 42 – Factors to Consider in
Choosing an NSAID
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
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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
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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
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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).
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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.
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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
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
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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