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Anti inflammatory Medications

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					    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).

                                              5
Figure 3-1: The
Inflammatory Response




                        6
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.



                                               7
      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
    marketplace in the spring of 1899.             9
 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 anti-
  inflammatory 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.

                                                17
      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 cross-
   reactivity 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 anti-
  inflammatory 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
                                            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.
                                           26
              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
     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 anti-
  inflammatory 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.
                                             45
 Box 3-7: Most Common
Indications for Injectable
     Corticosteroids




                             46
    Box 3-8: Potential
     Complications of
Injectable Corticosteroids




                         47

				
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