NSAIDs

Over-the-counter Over-the-counter management of inflammationmanagement of inflammation

Lon Kilgore, Ph.D.Lon Kilgore, Ph.D.USA Weightlifting Regional Development CenterUSA Weightlifting Regional Development Center Wichita Falls Weightlifting, Inc. Wichita Falls Weightlifting, Inc. Wichita Falls, Texas Wichita Falls, Texas

Inflammation DefinedInflammation Defined

A localized protective response elicited by injury A localized protective response elicited by injury or destruction of tissues, which serves to or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent destroy, dilute, or wall off both the injurious agent and the injured tissue. It is characterized in the and the injured tissue. It is characterized in the acute form by the classical signs of acute form by the classical signs of pain, heat, pain, heat, redness, swelling and loss of functionredness, swelling and loss of function. . Histologically, it involves a complex series of Histologically, it involves a complex series of events, including dilatation of arterioles, events, including dilatation of arterioles, capillaries, and venules, with increased capillaries, and venules, with increased permeability and blood flow, exudation of fluids, permeability and blood flow, exudation of fluids, including plasma proteins, and leukocytic including plasma proteins, and leukocytic migration into the inflammatory site.migration into the inflammatory site.

Symptoms of InflammationSymptoms of Inflammation

1 4 7 10 13 16S1

5.005.506.006.507.007.508.008.509.009.50

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Time in WeeksTime in Weeks

PPAAIINN

Low PainLow Pain

High PainHigh Pain

Pain – Swelling - Reduction in work capacity

American Academy of Orthopedic Surgeon epidemiological study reported 79% of recreational weight-trainers listed inflammation as their most common injury

Frequency of occurrence in athletes …

Moderate Work

Maximal Work

Moderate Work

Light Work

Sequence of Inflammatory EventsSequence of Inflammatory EventsStage 1 – Acute inflammation

Initial response to injury

Release of histamine, serotonin, bradykinin, prostaglandins, leukotrienes

Stage 2 – Immune response

Activation of immune cells (leukocytes)

Can be directed at pathogen or self

Stage 3 – Chronic inflammation

Release of interleukins, interferons, GMCSF, TNF, PDGF

Acute: Injury Pain Repair Clean-up

Chronic: Tissue destruction Pain Disability

Inflammatory EventsInflammatory Events

Findings: Increased force of shock increases Findings: Increased force of shock increases transcription of collagenase and gelatinase genes transcription of collagenase and gelatinase genes in synovial cellsin synovial cells

Interpretation: Training may disrupt joint Interpretation: Training may disrupt joint homeostasis. More intense training may be more homeostasis. More intense training may be more stressful.stressful.From Sun et al., 2004From Sun et al., 2004

Diagnosis of InflammationDiagnosis of Inflammation

Pain

Swelling

Reduction in work capacity

Reduced mobility

ESR

CRP

CK

AST

ALT

Myoglobinurua

Inflammatory Cells and CompetitionInflammatory Cells and Competition

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Leukocytes Lymphocytes Neutrophills

WBC numbers followed pattern of work induced WBC numbers followed pattern of work induced leukocytosis described as early as 1901.leukocytosis described as early as 1901.

C-Reactive Protein Response to CompetitionC-Reactive Protein Response to Competition

FINDINGS: CRP concentrations are significantly FINDINGS: CRP concentrations are significantly elevated at 72 hours after competition (p=0.04)elevated at 72 hours after competition (p=0.04)

INTERPRETATION: Inflammation occurs INTERPRETATION: Inflammation occurs following competition following competition

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Inflammatory Cell Response to TrainingInflammatory Cell Response to Training

FINDINGS: Although not statistically significant, FINDINGS: Although not statistically significant, monocyte numbers went downmonocyte numbers went down

INTERPRETATION: May indicate that training was INTERPRETATION: May indicate that training was stressful enough to cause exodus of monocytes from the stressful enough to cause exodus of monocytes from the blood in order to clean up and repair damaged tissue blood in order to clean up and repair damaged tissue (inflammation)(inflammation)

C-Reactive Protein Response to TrainingC-Reactive Protein Response to Training

FINDINGS: CRP was strongly correlated to FINDINGS: CRP was strongly correlated to training volume (r=0.74) and mildly correlated to training volume (r=0.74) and mildly correlated to intensity (r=0.47)intensity (r=0.47)

INTERPRETATION: Lots of training is potentially INTERPRETATION: Lots of training is potentially more inflammatory than very hard trainingmore inflammatory than very hard training

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Pre Week1 Week 2 Week 3 Week 4 Week 5

Inflammation in Power AthletesInflammation in Power AthletesSince these athletes work and play very hard … high Since these athletes work and play very hard … high volumes … high intensity … lots of compressive volumes … high intensity … lots of compressive forces … it’s a sure bet inflammation occursforces … it’s a sure bet inflammation occurs

Countermeasures to inflammationCountermeasures to inflammation

Typical Recommendations: Rest

Ice

Compression

Elevation

Countermeasures to inflammationCountermeasures to inflammation

Non-steroidal anti-inflammatory drugsNon-steroidal anti-inflammatory drugs

AspirinAspirin

AcetominophenAcetominophen

IbuprofenIbuprofen

NaproxenNaproxen

KetoprofenKetoprofen

Non-steroidal anti-inflammatory drug actionNon-steroidal anti-inflammatory drug action

PhospholipidPhospholipid

PhospholipaseAPhospholipaseA22 GlucocorticoidsGlucocorticoids

Arachidonic AcidArachidonic Acid

NSAIDNSAID CyclooxygenaseCyclooxygenase LipooxygenaseLipooxygenaseCOX-1, COX-1, COX-2COX-2

Cyclic EndoperoxidesCyclic Endoperoxides Hydroperoxy Eicosatetranoic Acid Hydroperoxy Eicosatetranoic Acid

ProstaglandinsProstaglandinsPGDPGD22, PGE, PGE22, PGF, PGF2α2α, PGI, PGI22 ThromboxaneThromboxane TXATXA22 Hydroxyeicosa tetranoic acidHydroxyeicosa tetranoic acid (HETE)(HETE) LeukotrienesLeukotrienesLTALTA44, LTB, LTB44, LTC, LTC44, LTD, LTD44, LTE, LTE44

Different NSAIDs block COX by different mechanisms (Tylenol vs. Aspirin)Different NSAIDs block COX by different mechanisms (Tylenol vs. Aspirin)

Different NSAIDs structure and action contribute to differing effectiveness Different NSAIDs structure and action contribute to differing effectiveness (Ibuprofen 20-30 times more effective than simple aspirin)(Ibuprofen 20-30 times more effective than simple aspirin)

Effectiveness of NSAIDsEffectiveness of NSAIDs

Recommended Dosage: Recommended Dosage: 325-650 mg 4-6 times per day325-650 mg 4-6 times per day

Lethal Dosage:Lethal Dosage: 20 g/day20 g/day

AspirinAspirin (acetylsalicylic acid)(acetylsalicylic acid) Most common "salicylate" analgesicMost common "salicylate" analgesic1. analgesic for mild to moderate pain1. analgesic for mild to moderate pain2. anti-pyretic (anti-fever)2. anti-pyretic (anti-fever)3. anti-inflammatory3. anti-inflammatory Also: anticoagulant action (used to prevent heart attack Also: anticoagulant action (used to prevent heart attack

or stroke due to clots); has anti-colon cancer, anti-skin or stroke due to clots); has anti-colon cancer, anti-skin cancer effects cancer effects

Adverse Effects of AspirinAdverse Effects of Aspirin1. Causes stomach irritation & bleeding1. Causes stomach irritation & bleeding3.3. Anticoagulant effect may be undesirable Anticoagulant effect may be undesirable 4.4. In those <16 yr with virus, flu or chicken pox, increased In those <16 yr with virus, flu or chicken pox, increased

risk of Reye's disease (serious liver & neurological risk of Reye's disease (serious liver & neurological disease)disease)

Signs of Taking Too Much AspirinSigns of Taking Too Much AspirinTinnitus, impaired hearing, nausea & vomiting, thirst, Tinnitus, impaired hearing, nausea & vomiting, thirst, rapid breathing, confusionrapid breathing, confusion

Effectiveness of NSAIDsEffectiveness of NSAIDs

Recommended Dosage: Recommended Dosage: 325-650 mg 4-6 times per day325-650 mg 4-6 times per day

Lethal Dosage:Lethal Dosage: 15-20 g/day15-20 g/day

AcetaminophenAcetaminophen (Tylenol, "non-aspirin pain reliever")(Tylenol, "non-aspirin pain reliever")• Same potency as aspirinSame potency as aspirin• Equal analgesic & antipyretic actionEqual analgesic & antipyretic action• Not anti-inflammatory or anticoagulantNot anti-inflammatory or anticoagulant• Less gastric distress & tinnitus, but more damaging to Less gastric distress & tinnitus, but more damaging to

liver with heavy useliver with heavy use• Can be used by those with aspirin allergy.Can be used by those with aspirin allergy.• No risk of Reye’s syndrome in kidsNo risk of Reye’s syndrome in kids

Effectiveness of NSAIDsEffectiveness of NSAIDs

Recommended Dosage: Recommended Dosage: 200 mg 4-6 times per day200 mg 4-6 times per day

Toxicity: Toxicity:

8 g/day results in hospitalization8 g/day results in hospitalization

IbuprofenIbuprofen (e.g. Motrin, Advil)(e.g. Motrin, Advil)1. More potent than aspirin or acetominophen 1. More potent than aspirin or acetominophen (take less)(take less)2. More effective for certain conditions 2. More effective for certain conditions ((inflammationinflammation, joint problems, , joint problems, sports injuriessports injuries, dysmenorrhea, dental pain), dysmenorrhea, dental pain)

3. Weaker anticoagulant effect than aspirin3. Weaker anticoagulant effect than aspirin4. GI irritant4. GI irritant5. 5000 count observation – increased likelihood of death from 5. 5000 count observation – increased likelihood of death from

end-stage renal failureend-stage renal failure

Boots 7268Boots 7268

Weed killer Weed killer turned turned

Pain killerPain killer

Effectiveness of NSAIDsEffectiveness of NSAIDs

Recommended Dosage: Recommended Dosage: 200 mg 2 times per day200 mg 2 times per day

Toxicity: Toxicity:

27.5 g/day caused hospitalization27.5 g/day caused hospitalization

LDLD5050 in dogs 100 mg/kg in dogs 100 mg/kg

Naproxen Naproxen (OTC Aleve; Naprosyn or Anaprox) (OTC Aleve; Naprosyn or Anaprox) 1. Very similar to ibuprofen but somewhat different time 1. Very similar to ibuprofen but somewhat different time

course course 2. Stronger stomach irritation compared to other NSAIDs & 2. Stronger stomach irritation compared to other NSAIDs &

should be avoided by those with kidney disease.should be avoided by those with kidney disease.3. Uses lower dosage3. Uses lower dosage

Naproxen’s Time courseNaproxen’s Time course7.7. Absorbed more slowly (peaks in 2-4 hrs) & stays longer Absorbed more slowly (peaks in 2-4 hrs) & stays longer

(binds to proteins in the blood). (binds to proteins in the blood). 2. If taken regularly, blood levels will be maintained by taking 2. If taken regularly, blood levels will be maintained by taking

just 2 doses a day. PDR states that pain relief lasts UP just 2 doses a day. PDR states that pain relief lasts UP TO 7- 8 hrs BUT FDA pushed 12 hr OTC dosing to limit TO 7- 8 hrs BUT FDA pushed 12 hr OTC dosing to limit risks.risks.

3. Naproxen sodium is absorbed faster.3. Naproxen sodium is absorbed faster.

Effectiveness of NSAIDsEffectiveness of NSAIDs

Recommended Dosage: Recommended Dosage: 12.5 mg 2 times per day12.5 mg 2 times per day

Toxicity: Toxicity:

5000 mg/day may induce GI symptoms5000 mg/day may induce GI symptoms

Ketoprofen Ketoprofen (e.g. Orudis, Actron)(e.g. Orudis, Actron)2.2. Same analgesic/anti-inflammatory familySame analgesic/anti-inflammatory family3.3. More potent, but otherwise not different in its effects/risks More potent, but otherwise not different in its effects/risks from other NSAIDs from other NSAIDs (about 1% incidence of some side effect)(about 1% incidence of some side effect)

Other considerations for NSAID useageOther considerations for NSAID useage

Increased appetiteIncreased appetite

Reduced hypertrophyReduced hypertrophy

AdditivesAdditives

CaffeineCaffeine

DiureticsDiuretics

Ephedra (*)Ephedra (*)

Alternative therapeutic measuresAlternative therapeutic measures

Lesson from Chinese herbal medicineLesson from Chinese herbal medicine

• Prepared cartilagePrepared cartilage

• CollagenCollagen

OK … as long as the active agent is

“unknown” some dork is still gonna be poppin’

chicken beaks so he can freakin’ squat!

• GlucosamineGlucosamine• Chondroitan SulfateChondroitan Sulfate

Mechanism of EffectMechanism of Effect

Glucosamine Sulfate and Chondroitan SulfateGlucosamine Sulfate and Chondroitan SulfateComponent of GlycosaminoglycansComponent of Glycosaminoglycans

Extra-cellular matrixExtra-cellular matrix

Growth factor mediationGrowth factor mediation

Shock absorptionShock absorption

Stabilization of cell membraneStabilization of cell membrane

Effectiveness of Glucosamine & ChondroitanEffectiveness of Glucosamine & Chondroitan

Recommended Dosage:Recommended Dosage:

1.5 g/day and 400-800 mg/day respectively1.5 g/day and 400-800 mg/day respectively

• Incorporated into cartilage in about 4 hours

• Stimulates proteoglycan synthesis

• Virtually no data on athletes BUT

• Arthritics has a 72% pain reduction by 7 days of supplementation

• Has proven to be more effective than Ibuprofen with chronic use

• Residual effect for up to 30 days after cessation

• Potentially may slow joint erosion or augment repair

An Apple a Day …An Apple a Day …

Flavonoids – Anti-oxidant neutraceuticalsFlavonoids – Anti-oxidant neutraceuticalsApples Apples (120 mg)(120 mg) Tea (69 mg)Tea (69 mg)

OnionsOnions (35 mg)(35 mg) Wine (40-150 mg)Wine (40-150 mg)

Chocolate (510 mg)Chocolate (510 mg) Beer (10-50 mg)Beer (10-50 mg)

Potato (8 mg)Potato (8 mg) Elderberry Juice (570 mg)Elderberry Juice (570 mg)Content per 100g or 100mlContent per 100g or 100ml

Summary and RecommendationsSummary and Recommendations

PhospholipidPhospholipid

PhospholipaseAPhospholipaseA22 GlucocorticoidsGlucocorticoids

Arachidonic AcidArachidonic Acid

NSAIDNSAID CyclooxygenaseCyclooxygenase LipooxygenaseLipooxygenaseCOX-1, COX-1, COX-2COX-2

Cyclic EndoperoxidesCyclic Endoperoxides Hydroperoxy Eicosatetranoic Acid Hydroperoxy Eicosatetranoic Acid

ProstaglandinsProstaglandinsPGDPGD22, PGE, PGE22, PGF, PGF2α2α, PGI, PGI22 ThromboxaneThromboxane TXATXA22 Hydroxyeicosa tetranoic acidHydroxyeicosa tetranoic acid (HETE)(HETE) LeukotrienesLeukotrienesLTALTA44, LTB, LTB44, LTC, LTC44, LTD, LTD44, LTE, LTE44

Summary and RecommendationsSummary and RecommendationsAll OTC NSAIDs are effective at reducing pain and or All OTC NSAIDs are effective at reducing pain and or inflammationinflammation

All OTC NSAIDS are COX inhibitors and carry with them a All OTC NSAIDS are COX inhibitors and carry with them a variety of side effectsvariety of side effects

Tylenol has the lowest effect on inflammationTylenol has the lowest effect on inflammation

Naproxen and Ketoprofen reduce the chance for side effects Naproxen and Ketoprofen reduce the chance for side effects and are least toxic of the OTC drugsand are least toxic of the OTC drugs

If maximal doses of OTC NSAIDs are ineffective, consult a If maximal doses of OTC NSAIDs are ineffective, consult a physician before using “prescription” doses OR get them to physician before using “prescription” doses OR get them to prescribe COX2 inhibitors to maximize relief to risk prescribe COX2 inhibitors to maximize relief to risk (Celebrex, etc.)(Celebrex, etc.)

Satellite cell activity suppression – As only about 5% of Satellite cell activity suppression – As only about 5% of muscular hypertrophy is derived from SC activity, it is likely muscular hypertrophy is derived from SC activity, it is likely more important to manage pain and train than to reduce more important to manage pain and train than to reduce loading and not use NSAIDs.loading and not use NSAIDs.

Summary and RecommendationsSummary and Recommendations

Consider using glucosamine or chondroitan sulfate Consider using glucosamine or chondroitan sulfate as an adjunct to NSAID therapyas an adjunct to NSAID therapy

Not appropriate for acute inflammationNot appropriate for acute inflammation

Not appropriate for intermittent useNot appropriate for intermittent use

Action is long lasting and as effective at reducing Action is long lasting and as effective at reducing pain as NSAIDspain as NSAIDs

May actually assist in tissue repairMay actually assist in tissue repair

May reduce the amount of NSAIDs consumedMay reduce the amount of NSAIDs consumed

Summary and RecommendationsSummary and Recommendations

Pay attention to fruit and vegetable consumptionPay attention to fruit and vegetable consumption

Consider decaffeinated teaConsider decaffeinated tea

Consider wine and beer consumption carefully. Consider wine and beer consumption carefully. Consumption has both risk and benefitConsumption has both risk and benefit

2 – 12 oz servings for males2 – 12 oz servings for males

1 – 12 oz serving for females1 – 12 oz serving for females