Anti-Inflammatory Agents

1
Anti-Inflammatory Agents

• ESAT 4001
• Pharmacology in Athletic Training

2
Effects of NSAIDS

• Analgesia
• Antipyresis
• Anticoagulation
• Control inflammation

3
Action of NSAIDs

• Hinder cyclooxygenase pathway
• Block synthesis of prostaglandins and
  thromboxanes
• prostaglandins and thromboxanes involved in
  production of pain, inflammation, fever and
  excessive blood clotting
• NSAIDs inhibit platelet formation decreased
  thrombus formation
• 2 reasons this may be counterproductive
• Tissue trauma while taking for tendinitis
• If started immediately following trauma platelet
  aggregation may be affected

4
Side Effects of NSAIDs

• GI irritation/damage
• Irritation of gastric mucosa
• Inhibition of prostaglandins
• Hepatic and renal disorders
• Some studies indicate aspirin and other NSAIDs
  inhibit synthesis of some components of
  connective tissue

5
Side Effects Specific to Aspirin

• Overdose
• SS headache, tinnitus, hearing difficulties,
  confusion, GI irritation
• Reyes syndrome
• SS high fever, vomiting, liver dysfunction,
  decreasing level of alertness
• Hypersensitivity
• Allergic reactions bronchospasms, hives, sever
  rhinitis
• Possibility of CV shock in these people

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Classes of NSAIDs
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Acetic Acids Products

• Indomethacin
• Indocine
• One of the strongest cyclooxygenase inhibitors
• Typically fully excreted w/in 48 hours
• Diclofenac
• Voltaren cataflam
• Absorbed rapidly, short half-life

8
Acetic Acids Products

• Sulindac
• Clinoril
• Structurally/pharmacologically related to
  indomethacin
• Prodrug
• Converted to active sulfide metabolite
• Sulfide metabolite is 500 times more potent as a
  cyclooxygenase inhibitors than parent drug

9
Acetic Acids Products

• Tolmetin
• Tolectin
• Arthritis
• Rapid absorption and elimination
• Complete excretion w/in 24 hours
• Common side effects nausea and vomiting

10
Acetic Acids Products

• Ketorolac
• Toradol
• Excellent analgesic effects w/o side affects of
  morphine
• Loading dose (IM or IV)
• Rapid absorption
• Common side effects associated with acetic acid
  products
• Abdominal pain, headache, dizziness, and tinnitus

11
Enolic Acids

• Phenylbutazone
• Butazolidin
• Originally, was first NSAID alternative to
  aspirin
• Has been found to be potentially fatal
• Used only in short-term treatment (gout)
• Side effects bone marrow depression, decreased
  production of platelets and RBCs
• Not often used in athletic medicine

12
Enolic Acids

• Piroxicam
• Feldene
• Long half-life one-a-day dosage
• Rapid absorption, long action
• Side effects GI symptoms, dizziness, tinnitus,
  and headache most commonly reported
• Taking w/ food does not effect absorption, but
  does decrease gastric symptoms

13
Fenamic Acid Derivatives

• Meclofenamate
• Meclomen
• Rapid absorption
• Peak effect of drug w/in .5-2 hours
• Common side effects of all NSAIDs
• Side effects tend to be more common

14
Propionic Acids

• Ibuprofen
• Advil, Motrin, Nuprin
• Used more often for analgesic effect than for
  anti-inflammatory effect
• Analgesic effects in 2-4 hours
• Anti-inflammatory effects require days to weeks
• Absorption slowed when taking w/ food, however
  total absorption is unaffected
• Maximum dose 3200 mg/day
• Self-medication is common

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Propionic Acids

• Ketoprofen
• Orudis
• Absorbed rapidly and completely
• Analgesia w/in 1 hr last 3-4 hrs
• Upset stomach (dyspepsia) most common side effect

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Propionic Acids

• Naproxen
• Aleve, Naprosyn, Anaprox
• Better patient tolerance than aspirin and
  indomethacin
• Aleve loading dose of 440 mg followed by 220 mg
  12 hr later
• 660 mg daily max or 10 days of treatment
• Half-life of 10-20 hr.

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Propionic Acids

• Fenoprofen
• Nalfon
• GI irritation is common
• Taken w/ food decreases GI side effect
• Delays absorption, decreased peak plasma
  concentration
• Analgesic effects w/in 15-30 m., lasts 4-6 hr.
• Half-life 2.5-3.0 hr, q 4-6 hr.

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Carboxylic Acids

• Aspirin
• 1st NSAID introduced
• Prodrug inactive until metabolized into
  constituent parts
• Liver
• Permanently binds to platelets producing
  anticoagulant effect up to 10 days
• Each tablet 325 mg

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Carboxylic Acids

• Diflunisal
• Dolobid
• Good anti-inflammatory and analgesic effects
• Poor antipyretic
• Loading does of 1 g, followed by 500 mg every
  8-12 hours as needed

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Adrenal Steroid Compounds

• Glucocorticoids
• Most frequently used in athletics
• Excellent anti-inflammatory response
• Effects include reduction of tissue heat,
  reduction of erythema, control of swelling,
  decreased local temperature

21
Glucocorticoid

• Action
• Works by inhibiting prostaglandin and leukotriene
  production
• Also impair function of macrophages and
  leukocytes
• Side effects/precautions
• Catabolic effect not limited to target structures
• Injection directly into ligament or tendon will
  weaken structure for 2-6 weeks
• Repeated injections into a joint can lead to
  intra-articular degeneration and arthritis.

22
Types of Glucocorticoids

• Cortisone
• Short-acting (8-12 hr)
• Often provided in pill form in a dose pack
• Long term use can be harmful
• Can be used to prevent/suppress inflammation, and
  suppress immune reactions

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Types of Glucocorticoids

• Hydrocortisone
• Administered orally, topically, or by injection
• Peak effect w/in 1-2 hr
• Duration dependant on injection site
• Average duration is 8-12 hr

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Types of Glucocorticoids

• Prednisone
• Most commonly prescribed oral corticosteroid
• 4x more potent than Hydrocortisone
• Intermediate acting
• Duration of action is 18-36 hr.
• Metabolized in liver to active form prednisolone

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Types of Glucocorticoids

• Dexamethasone
• Decadron
• Anti-inflammatory and immunosuppressive uses
• Administered enterally and parenterally
• Injection or iontophoresis
• Longest acting glucocorticoid
• Duration of action from 1-3 days