Anti-Inflammatory Agents ESAT 4001 Pharmacology in Athletic Training.

Anti-Anti-Inflammatory Inflammatory

AgentsAgentsESAT 4001ESAT 4001

Pharmacology in Athletic Pharmacology in Athletic TrainingTraining

Effects of NSAIDSEffects of NSAIDS

AnalgesiaAnalgesia AntipyresisAntipyresis AnticoagulationAnticoagulation Control inflammationControl inflammation

Action of NSAIDsAction of NSAIDs

Hinder cyclooxygenase pathwayHinder cyclooxygenase pathway Block synthesis of prostaglandins and Block synthesis of prostaglandins and

thromboxanesthromboxanes prostaglandins and thromboxanes involved prostaglandins and thromboxanes involved

in production of pain, inflammation, fever in production of pain, inflammation, fever and excessive blood clottingand excessive blood clotting

NSAIDs inhibit platelet formation = NSAIDs inhibit platelet formation = decreased thrombus formationdecreased thrombus formation 2 reasons this may be counterproductive2 reasons this may be counterproductive

Tissue trauma while taking for tendinitisTissue trauma while taking for tendinitis If started immediately following trauma platelet If started immediately following trauma platelet

aggregation may be affectedaggregation may be affected

Side Effects of NSAIDsSide Effects of NSAIDs

GI irritation/damageGI irritation/damage Irritation of gastric mucosaIrritation of gastric mucosa Inhibition of prostaglandinsInhibition of prostaglandins

Hepatic and renal disordersHepatic and renal disorders Some studies indicate aspirin and Some studies indicate aspirin and

other NSAIDs inhibit synthesis of other NSAIDs inhibit synthesis of some components of connective some components of connective tissuetissue

Side Effects Specific to Side Effects Specific to AspirinAspirin

OverdoseOverdose S&S – headache, tinnitus, hearing difficulties, S&S – headache, tinnitus, hearing difficulties,

confusion, & GI irritationconfusion, & GI irritation Reye’s syndromeReye’s syndrome

S&S – high fever, vomiting, liver dysfunction, S&S – high fever, vomiting, liver dysfunction, & decreasing level of alertness& decreasing level of alertness

HypersensitivityHypersensitivity Allergic reactions – bronchospasms, hives, Allergic reactions – bronchospasms, hives,

sever rhinitissever rhinitis Possibility of CV shock in these peoplePossibility of CV shock in these people

Classes of NSAIDsClasses of NSAIDs

Acetic Acids ProductsAcetic Acids Products

IndomethacinIndomethacin IndocineIndocine One of the strongest cyclooxygenase One of the strongest cyclooxygenase

inhibitorsinhibitors Typically fully excreted w/in 48 hoursTypically fully excreted w/in 48 hours

DiclofenacDiclofenac Voltaren & cataflamVoltaren & cataflam Absorbed rapidly, short half-lifeAbsorbed rapidly, short half-life


SulindacSulindac ClinorilClinoril Structurally/pharmacologically related Structurally/pharmacologically related

to indomethacinto indomethacin ProdrugProdrug

Converted to active sulfide metaboliteConverted to active sulfide metabolite Sulfide metabolite is 500 times more potent Sulfide metabolite is 500 times more potent

as a cyclooxygenase inhibitors than parent as a cyclooxygenase inhibitors than parent drugdrug


TolmetinTolmetin TolectinTolectin ArthritisArthritis Rapid absorption and eliminationRapid absorption and elimination

Complete excretion w/in 24 hoursComplete excretion w/in 24 hours Common side effects – nausea and Common side effects – nausea and

vomitingvomiting


KetorolacKetorolac ToradolToradol Excellent analgesic effects w/o side Excellent analgesic effects w/o side

affects of morphineaffects of morphine Loading dose (IM or IV)Loading dose (IM or IV) Rapid absorptionRapid absorption

Common side effects associated with Common side effects associated with acetic acid productsacetic acid products Abdominal pain, headache, dizziness, Abdominal pain, headache, dizziness,

and tinnitusand tinnitus

Enolic AcidsEnolic Acids

PhenylbutazonePhenylbutazone ButazolidinButazolidin Originally, was first NSAID alternative Originally, was first NSAID alternative

to aspirinto aspirin Has been found to be potentially fatalHas been found to be potentially fatal

Used only in short-term treatment (gout)Used only in short-term treatment (gout) Side effects – bone marrow depression, Side effects – bone marrow depression,

decreased production of platelets and decreased production of platelets and RBCsRBCs

Not often used in athletic medicineNot often used in athletic medicine

Enolic AcidsEnolic Acids

PiroxicamPiroxicam FeldeneFeldene Long half-life ~ one-a-day dosageLong half-life ~ one-a-day dosage Rapid absorption, long actionRapid absorption, long action Side effects – GI symptoms, dizziness, Side effects – GI symptoms, dizziness,

tinnitus, and headache most commonly tinnitus, and headache most commonly reportedreported

Taking w/ food does not effect Taking w/ food does not effect absorption, but does decrease gastric absorption, but does decrease gastric symptomssymptoms

Fenamic Acid DerivativesFenamic Acid Derivatives

MeclofenamateMeclofenamate MeclomenMeclomen

Rapid absorptionRapid absorption Peak effect of drug w/in .5-2 hoursPeak effect of drug w/in .5-2 hours

Common side effects of all NSAIDsCommon side effects of all NSAIDs Side effects tend to be more commonSide effects tend to be more common

Propionic AcidsPropionic Acids

IbuprofenIbuprofen Advil, Motrin, NuprinAdvil, Motrin, Nuprin Used more often for analgesic effect than for Used more often for analgesic effect than for

anti-inflammatory effectanti-inflammatory effect Analgesic effects in 2-4 hoursAnalgesic effects in 2-4 hours Anti-inflammatory effects require days to weeksAnti-inflammatory effects require days to weeks Absorption slowed when taking w/ food, Absorption slowed when taking w/ food,

however total absorption is unaffectedhowever total absorption is unaffected Maximum dose = 3200 mg/dayMaximum dose = 3200 mg/day Self-medication is commonSelf-medication is common


KetoprofenKetoprofen OrudisOrudis Absorbed rapidly and completelyAbsorbed rapidly and completely Analgesia w/in 1 hr ~ last 3-4 hrsAnalgesia w/in 1 hr ~ last 3-4 hrs Upset stomach (dyspepsia) most Upset stomach (dyspepsia) most

common side effectcommon side effect


NaproxenNaproxen Aleve, Naprosyn, AnaproxAleve, Naprosyn, Anaprox Better patient tolerance than aspirin Better patient tolerance than aspirin

and indomethacinand indomethacin Aleve – loading dose of 440 mg followed Aleve – loading dose of 440 mg followed

by 220 mg 12 hr laterby 220 mg 12 hr later 660 mg daily max or 10 days of treatment660 mg daily max or 10 days of treatment

Half-life of 10-20 hr.Half-life of 10-20 hr.


FenoprofenFenoprofen NalfonNalfon GI irritation is commonGI irritation is common Taken w/ food decreases GI side effectTaken w/ food decreases GI side effect

Delays absorption, decreased peak plasma Delays absorption, decreased peak plasma concentrationconcentration

Analgesic effects w/in 15-30 m., lasts 4-Analgesic effects w/in 15-30 m., lasts 4-6 hr.6 hr.

Half-life = 2.5-3.0 hr, q 4-6 hr. Half-life = 2.5-3.0 hr, q 4-6 hr.

Carboxylic AcidsCarboxylic Acids

AspirinAspirin 11stst NSAID introduced NSAID introduced Prodrug – inactive until metabolized Prodrug – inactive until metabolized

into constituent partsinto constituent parts LiverLiver

Permanently binds to platelets ~ Permanently binds to platelets ~ producing anticoagulant effect up to 10 producing anticoagulant effect up to 10 daysdays

Each tablet = 325 mgEach tablet = 325 mg

Carboxylic AcidsCarboxylic Acids

DiflunisalDiflunisal DolobidDolobid Good anti-inflammatory and analgesic Good anti-inflammatory and analgesic

effectseffects Poor antipyreticPoor antipyretic Loading does of 1 g, followed by 500 mg Loading does of 1 g, followed by 500 mg

every 8-12 hours as neededevery 8-12 hours as needed

Adrenal Steroid Adrenal Steroid CompoundsCompounds

GlucocorticoidsGlucocorticoids Most frequently used Most frequently used

in athleticsin athletics Excellent anti-Excellent anti-

inflammatory responseinflammatory response Effects include: Effects include:

reduction of tissue reduction of tissue heat, reduction of heat, reduction of erythema, control of erythema, control of swelling, & swelling, & decreased local decreased local temperaturetemperature

GlucocorticoidGlucocorticoid

ActionAction Works by inhibiting prostaglandin and Works by inhibiting prostaglandin and

leukotriene productionleukotriene production Also impair function of macrophages and Also impair function of macrophages and

leukocytesleukocytes Side effects/precautionsSide effects/precautions

Catabolic effect not limited to target structuresCatabolic effect not limited to target structures Injection directly into ligament or tendon will Injection directly into ligament or tendon will

weaken structure for 2-6 weeksweaken structure for 2-6 weeks Repeated injections into a joint can lead to intra-Repeated injections into a joint can lead to intra-

articular degeneration and arthritis.articular degeneration and arthritis.

Types of GlucocorticoidsTypes of Glucocorticoids

CortisoneCortisone Short-acting (8-12 hr)Short-acting (8-12 hr) Often provided in pill form in a dose Often provided in pill form in a dose

packpack Long term use can be harmfulLong term use can be harmful Can be used to prevent/suppress Can be used to prevent/suppress

inflammation, and suppress immune inflammation, and suppress immune reactionsreactions


HydrocortisoneHydrocortisone Administered orally, topically, or by Administered orally, topically, or by

injectioninjection Peak effect w/in 1-2 hrPeak effect w/in 1-2 hr Duration dependant on injection siteDuration dependant on injection site Average duration is 8-12 hrAverage duration is 8-12 hr


PrednisonePrednisone Most commonly prescribed oral Most commonly prescribed oral

corticosteroidcorticosteroid 4x more potent than Hydrocortisone4x more potent than Hydrocortisone Intermediate actingIntermediate acting

Duration of action is 18-36 hr.Duration of action is 18-36 hr. Metabolized in liver to active form Metabolized in liver to active form

prednisoloneprednisolone


DexamethasoneDexamethasone DecadronDecadron Anti-inflammatory and Anti-inflammatory and

immunosuppressive usesimmunosuppressive uses Administered enterally and parenterallyAdministered enterally and parenterally

Injection or iontophoresisInjection or iontophoresis Longest acting glucocorticoidLongest acting glucocorticoid

Duration of action from 1-3 daysDuration of action from 1-3 days

Anti-Inflammatory Agents ESAT 4001 Pharmacology in Athletic Training.

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