Anti-Inflammatory Drugs

Most Commonly used

Medications in Athletics and
Physically Active Populations
Case Study
A 20 yo cross country runner
complains of pain in her foot. She
runs more than 35 miles per week
and has been having foot pain for
almost 10 days. She ask you
whether she should take aspirin,
Advil or Alleve
What should you do??
Goals
History of AI & NSAIDs
Bodys response to injury
How AI & NSAIDs mediate the injury
response
Common AI & NSAIDS used
Indication, Contra etc
History of NSAIDs
Hippocrates - chewing of willow bark for a
variety of ailments
MacLagan (1876) - extracted a portion of
the willow bark called salicia
1899, A German pharmaceutical company,
Bayer, developed acetylsalicylic acid called
Aspirina

NSAIDs
Mainstay of pharmacological therapy for
the TX of soft tissue injuries
When added to ICES, NSAIDs may quicken
the return to activity because of enhanced
pain relief and swelling reduction
Allows athlete to participate with minor and
moderate injuries
Rates
1980s over 14 million people use NSAIDs
regularly for arthritis
80% use daily
Prescription NSAIDs increased from 50
million annually in 1980s to 70 million
annually in the 1990s
Alarming increase due to number of NSAIDs
available as OTC
Injury Response Changes in
Microcirculation
Whole cap. bed @ damages site overfills
with blood
All cap. dilate (injury and non-injury)
Venues dilate = inc. blood flow in draining
veins
Inc. blood flow to central cap and vessels
Overflow then spreads to peripheral tissues
Stasis of blood in injured area
Chemical Mediators
Numerous chemical involve to
increase leakage of blood and
fluid
histamines
kinins
protagladins
Prostagladins
Found in almost every tissue and body
fluid
Causes:
Inc. VD at low levels but the bleeding is
long lasting
Inc. vascular permeability and pain
producing activity of other substances
Cyclooxygenase (COX)
Responsible for assisting in
prostaglandin synthesis for
inflammation, fever and sensitizing
nerves
1999 COX 1 and COX 2 were
identified to inhibit prostaglandin
synthesis
Cyclooxygenase (COX)
COX 2
Celecoxib
(Celebrex)
Meloxicam (Mobic)
Rofecoxib (Vioxx)
AI Agents
Over 20 categories available
3 OTC
All proven effective
No clear indication 1 drug is better than
another
Exact mechanism of how they work is
unclear (several possible theories)
Decisions
Steroidal v nonsteriodal
Injectable, oral or topical
Salicylic or nonsalicyclic
Short or long acting

Success depends upon
past experiences
Prescribing preference of
MD

Types of AI Agents
Glucocorticiods Fairly strong AI Short Acting
cortisone %
hydrocortisone
Intermediate Acting
Prednisone
NSAID
(non-Opioid)
TX mild to
moderate pain,
fever and
inflammation
NSAIDs Dosages
Bimodal effect
Low dose = analgesic effect
High dose = AI effect
Common AI Drugs
Aspirin
Diclofenac (Cataflam,
Voltaren
Ibuprofen
Indomethacin (Indocin)
Naproxen
Piroxicam (Feldene)
Sulindac (Clinoril)
Aspirin
Most commonly taken drug
Over 20,000 tons ingested annually
in US
Leading OTC cause of adverse
drug reaction causing
hospitalization
ASA
Main Action
Diminish synthesis and
release of prostaglandin
ASA
Dissolves in stomach and SI
Enteric coating delays
dissolution and thus inc. time
for effect to occur
Brand has no TX effect
ASA
Extremely effective for a variety of
conditions
Relatively safe w/n recommended dosages
cheap
safe for self treatment
can be used for injury or for prevention of
muscle soreness
ASA Contraindications
HX of GI bleeding
Bleeding disorders
Use Cautiously with:
Renal disease
Pregnancy (avoid 3
rd
trimester)
Lactation
Children or adolescents
Reyes Syndrome
Seen in children <15 yo after viral URI
Cause is UK but associated with increased use of
ASA
Symptoms nausea, vomiting, change in mental
status, encephalopathy and altered live function
ASA should not be used an an antipyretic or
for an reason in tx children with viral
infections
Dosage
Analgesia & Antipyretic
325-500 mg q 3 h
325-600 mg q 4 h
650-1000 mg q 6 h
Do not exceed 4 g/day
Anti-Inflammatory
3.6-5.4 g/day divided equally
Dosage
Prevention of Myocardial Infarction
300-325 mg/day
Doses as low as 80 mg/day may be effective
Prevention of Transient Ischemic Attack
1-1.3 g daily in 2-4 divided doses
Doses as low as 325 mg/day may be used in
patient who are intolerant of high doses
Time Action Profile
Onset Peak Duration Half Life
5-30 min 1-3 hr 3-6 hr 2-3 hr low dose
15-30 hr high dose
Time Action Profile
Drug Onset Peak Duration Half Life
Naproxen 1 hr UK ~ 7 hrs 10-20 hr
Ibuprofen 30 min 1-2 hr 4-6 hr 2-4 hr
Indomethacin 30 min 0.5-2 hr 4-6 hr 2.6-11
hrs
Piroxicam 1 hr UK 48-72
hrs
50 hrs
Diclofenac 1-2 dys 2 wks + UK 1.2-2 hrs
NSAIDs Side Effects
Occurs in 30% of users
Most common: GI irritation
Kidneys
inc fluid retention
dec Na retention
dec kidney output
All effects are reversible when drug is stopped

Contraindications
Children
Pregnancy
Pre-existing renal or hepatic
pathology
Active peptic ulcer
Corticosteriods
One of the most powerful AI
medications available
Classified as glucocorticoids
Cortisone, hydrocortisone, prednisone
Used in the management of chronic
disease and injury
Inflammation & allergic
Corticosteriods
Discovered in 1949
Very effective in the TX of
inflammatory conditions
Large number of adverse effects
Effective for short term, acute
situations
Chemical Make-Up
Hydrocortisone or cortisol is the primary
agent
Glucocorticoid, which is naturally secreted
by body is derivative
Currently, many AI steroids are available
more powerful than cortisol, but have the
same chemical structure as glucocorticoid
Chemical Make-Up
Long term use will inhibit
bodys glucocorticoid
activity and the bodys
ability to produce this
substance naturally
How it Works
Reduces output of chemical
mediators
Reduction in edema
Clinical Application
Direct application to
inflamed area
Tendon sheaths and bursae
respond best
Little systemic effects
Time Action Profile
Drug Onset Peak Duration Half Life
Cortisone PO rapid 2 hrs 1.25-1.5
dys
8-12 hrs
Cortisone IM slow 20-48
hrs
1.25-1.5
dys
Prednisolone
PO
UK 1-2 hrs 1.25-1.5
dys
18-36
hrs
Topical Application
Well absorbed
Large portion of drug is transported
away by blood
Accumulation in mm and connective
tissue is limited
Can cause thinning of skin and slow
down wound healing
Doping Control
Stringent regulations by IOC
Topical application is allowed
Intraarticular injection is
permissible but must be declared
General systemic application is
banned
Side Effects
Osteoporosis
Weakening of skeletal structure
Weakening of muscular
structure
Other Side Effects
Glucose intolerance
Hypotension
Capillary fragility
Psychological changes
Diminished wound healing
All side effects are dose related
Dimethyl Sulfoxide (DMSO)
Drug of question - used with
animals and to clean floors
Highly effective in the reduction of
edema
Clinical trials inconclusive or were
stopped (changes in eyes)
DMSO
FDA approved 50% solution for TX of
cystitis
Canada approved 70% solution for TX of
Scleroderma
Vets approved 90% solution for TX of
edema
Public gets 99% industrial solution
approved for degreasing
DMSO
When applied, absorbed everything
Side effects
Garlic odor
Bad taste in mouth
Skin irritation
I firmly believe that if all the
medicines could be sunk to the
bottom of the sea, it would be
better for mankind -- and all
the worst for the fishes.
Oliver Wendell Holmes, 1980