Chapter 5 Headache

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Headache:Introduction
Worldwide,47%ofthepopulationsuffersfromheadacheatanygiventime,and66%willsufferfromheadacheatsome
pointintheirlives.Migraineheadacheismoresevereanddebilitatingcomparedwithtensiontypeheadache.However,
theoveralldiseaseburdentosocietyissimilarbetweenthetwoheadachetypesbecause38%ofthepopulationsuffers
fromtensiontypeheadacheand10%frommigraine.1
Manyheadachesufferersselftreatwithnonprescriptionremediesratherthanseekmedicalattention.Asmuchastwo
thirdsofnonprescriptionanalgesicusemaybeforheadache.2 Onestudy2 foundthat24%ofpatientschronically
overusedmedicationandonly14.5%hadeverbeenadvisedtolimittheirintakeofacuteheadachetreatments.Clearly,
anopportunitytoimprovemedicationuseexistsamongpatientsselftreatingforvariouspainsyndromes.
Headachesaregenerallyclassifiedasprimaryorsecondary.Primaryheadaches(approximately90%ofheadaches)are
notassociatedwithanunderlyingillness.Examplesincludeepisodicandchronictensiontypeheadaches,migraine
headachewithandwithoutaura,clusterheadaches,andmedicationoveruseheadaches.Secondaryheadachesare
symptomsofanunderlyingcondition,suchasheadtrauma,stroke,substanceabuseorwithdrawal,bacterialandviral
diseases,anddisordersofcraniofacialstructures.
Thischapterfocusesonthemostcommonheadachesthatareamenabletoselftreatment:tensiontype,diagnosed
migraine,andsinusheadaches.Nonprescriptionanalgesicsareusefulintreatingheadache,eitherasmonotherapyor
asadjunctstononpharmacologicorprescriptiontherapy.
Tensiontypeheadaches,alsocalledstressheadaches,canbeepisodicorchronic.Chronicheadachesoccur15or
moredayspermonthforatleast3months.1 Theprevalenceoftensiontypeheadacheisgreatestintheagerange4049
years,occursinaratioof5:4ofwomentomen,andincreaseswithhigherlevelsofeducation.3
TheprevalenceofmigraineheadacheintheUnitedStatesisabout18%forwomenand6%formen.Onsetusually
beginsinthefirstthreedecadesoflife,withgreatestprevalenceataroundage40.Amongchildren,boysandgirlsare
affectedequally,butattacksusuallygreatlydecreaseinboysafterpuberty.4 Migrainewithoutaura(i.e.,neurologic
symptomsthatprecedetheheadpain)occursalmosttwiceasfrequentlyasmigrainewithaura,andmanyindividuals
mayhavebothtypesofheadaches.Upto70%ofpatientswithmigrainehavefamilyhistoriesofmigraine,suggesting
thatthisdiseaseisinfluencedbyheredity.
Theeconomicimpactofmigraineheadacheissubstantial.Directcostsformedicalserviceshavebeenestimatedat
$1billionintheUnitedStates.Agreaterburdencomesfromlostproductivityandwages,withmigrainecosting$13
billionforAmericanemployers.Migraineheadachesaffecthealthrelatedqualityoflifeinamannersimilartothatof
depression.4
Headacheisafrequentlyreportedsymptominpatientswithacutesinusitis.Thesepatientsalsoexperienceothersinus
symptomssuchastoothacheintheupperteeth,facialpain,nasalstuffiness,andnasaldischarge.Theprevalenceof
sinusheadacheislow,andupto90%ofpatientswhobelievetheyhavesinusheadachemayactuallybeexperiencing
migraineheadache.5
PathophysiologyofHeadache
Tensiontypeheadachesoftenmanifestinresponsetostress,anxiety,depression,emotionalconflicts,andotherstimuli.
Theepisodictensiontypeheadachesubtypeisthoughttohaveaperipheralpainsource,whereasthechronictension
typeheadachehasacentralmechanism.Ageneticcomponentappearstoinfluencethepresenceorabsenceoftension
typeheadache.Furthermore,itislikelythattensiontypeandmigraineheadachesharepathophysiologicfeatures,
makingthemmoresimilarthandistinct.6 Migraineheadachesprobablyarisefromacomplexinteractionofneuronaland
vascularfactors.Stress,fatigue,irregularsleeppatterns,fastingoramissedmeal,vasoactivesubstancesinfood,
caffeine,alcohol,changesinfemalehormones,changesinbarometricpressureandaltitude,lights,odor,neckpain,
exercise,andsexualactivitymaytriggermigraine.7 Medications(e.g.,reserpine,nitrates,oralcontraceptives,and
postmenopausalhormones)canalsotriggermigraine.Althoughtheirroleinmigraineheadacheisstilldebated,
personalityfeaturesofmigrainesufferersincludeperfectionism,rigidity,andcompulsiveness.Menstrualmigraines
appearatthemenstrualstageoftheovariancycleandoccurinlessthan10%ofwomen.Forsomewomen,these
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migraineheadachesoccuratspecifictimesbefore,after,orduringthemenstrualcycle.
Mostinvestigationintothepathophysiologyofheadachehascenteredonmigraineheadache.Thebestevidence
suggeststhatmigraineoccursthroughdysfunctionofthetrigeminovascularsystem.Neuronaldepolarizationthat
spreadsslowlyacrossthecerebralcortexisobservedduringtheauraphase.Magnesiumdeficiencymaycontributeto
thisstate.Duringtheheadachephase,stimulation(byanaxonreflex)oftrigeminalsensoryfibersinthelargecerebral
andduralvesselscausesneuropeptidereleasewithconcomitantneurogenicinflammation,vasodilation,andactivation
ofplateletsandmastcells.Menstrualmigrainepathophysiologyoccursthroughestrogenwithdrawalfollowedby
serotoninwithdrawal.Decreasedserotoninisassociatedwithincreasedcalcitoningenerelatedpeptideandsubstance
Pfromtrigeminalnerves,whichleadtovasodilationofvesselsandsensitivityofthetrigeminalnerves.Estrogenmayalso
influencenitricoxide,magnesium,orprostaglandins,whichmaycontributetothemenstrualmigraine.8,9 Sinus
headacheoccurswheninfectionorblockageoftheparanasalsinusescausesinflammationordistensionofthesensitive
sinuswalls(seeChapter11).Pathophysiologicmechanismsatworkduringmigraineheadachecanproduceprominent
sinuscongestion.
Medicationoveruseheadacheresultsfromareboundeffectafterthewithdrawalofananalgesic.Thistypeofheadache
differsfromaheadacherelatedtoamedicationsideeffect.Somepatientswhosufferfrommigraineortension
headachesreceivesomerelieffromnonprescriptionmedication,andovertimemayincreasetheiruseofthe
nonprescriptiontreatment,whichcanleadtomedicationoveruseheadaches.Theseheadachesareusuallyassociated
withfrequentuse(morethantwiceweekly)for3monthsorlongerandoccurwithinhoursofstoppingtheagentre
administrationoftheagentprovidesrelief.10 Agentsassociatedwithmedicationoveruseheadachesare
acetaminophen,somenonsteroidalantiinflammatorydrugs(NSAIDs),aspirin,caffeine,triptans,opioids,butalbital,and
ergotamineformulations.10 Symptomatologyshiftsfromthebaselineheadachetypetoanearlycontinuousheadache,
particularlynoticeableonawakening.
ClinicalPresentationofHeadache
HeadachescanbedifferentiatedbytheirsignsandsymptomsthemajordefiningcharacteristicsarelistedinTable51.
Theseverityofpainassociatedwithtensiontypeheadachesishighlyvariable.Someheadachesaresomildtheydonot
requiretreatment,whereasothersaresufficientlyseveretobedisabling.Shiveringorcoldtemperaturesmayincrease
painfromtensiontypeheadaches.Chronictensiontypeheadachesoccurringatleast15dayspermonthforatleast6
monthsmaybeamanifestationofpsychologicalconflict,depression,oranxiety.Theseheadachesmaybeassociated
withsleepdisturbances,shortnessofbreath,constipation,weightloss,fatigue,decreasedsexualdrive,palpitations,and
menstrualchanges.
Migraineheadachesareclassifiedasmigrainewithorwithoutaura.Auramanifestsasaseriesofneurologicsymptoms:
shimmeringorflashingareas,blindspots,visualandauditoryhallucinations,muscleweaknessthatisusuallyonesided,
anddifficultyspeaking(rarely).Thesesymptomsmaylastupto30minutes,andthethrobbingheadachepainthatfollows
maylastfromseveralhoursto2days.Migraineswithoutaurabeginimmediatelywiththrobbingheadachepain.Both
formsofmigraineoftenareassociatedwithnausea,vomiting,photophobia,phonophobia,sinussymptoms,tinnitus,light
headedness,vertigo,andirritability,andareaggravatedbyroutinephysicalactivity.Premonitary(prodrome)symptoms
inmigrainecanbeneuropsychiatric(e.g.,anxiety,irritability,yawning,unhappiness,andinsomnia),sensory(e.g.,
phonophobia,photophobia,focusingdifficulties,andspeechdifficulties),digestive(e.g.,foodcraving,nausea,vomiting,
diarrhea,andconstipation),andgeneral(e.g.,asthenia,tiredness,fluidretention,andurinaryfrequency).11
Sinusheadacheisusuallylocalizedtofacialareasoverthesinusesandisdifficulttodifferentiatefrommigrainewithout
aura.Thepainqualityofasinusheadacheistypicallyadullandpressurelikesensation.Stoopingorblowingthenose
oftenintensifiesthepainofsinusheadache,buttheheadacheisnotaccompaniedbynausea,vomiting,orvisual
disturbances.Persistentsinuspainand/ordischargesuggestspossibleinfectionandrequiresreferralformedical
evaluation.
TreatmentofHeadache
TreatmentGoals
Thegoalsoftreatingheadacheare(1)toalleviateacutepain,(2)torestorenormalfunctioning,(3)topreventrelapse,
and(4)tominimizesideeffects.Forchronicheadache,anadditionalgoalistoreducethefrequencyofheadaches.
GeneralTreatmentApproach
Mostpatientswithepisodicheadachesrespondadequatelytoselftreatmentwithnonpharmacologicinterventions,
nonprescriptionmedications,orboth.However,somepatientswithepisodicheadachesandmostwithchronic
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headachesarecandidatesforprescriptiontreatments.Throughoutthischapter,theabbreviationNSAIDwillbeusedto
denotetheclassofnonsalicylatenonsteroidalantiinflammatorydrugs(e.g.,ibuprofenandnaproxen).
TABLE51CharacteristicsofTensionType,Migraine,andSinusHeadaches
TensionTypeHeadache
MigraineHeadache
SinusHeadache
Location
Bilateral
Overthetopofthehead,
extendingtobaseofskull
Usuallyunilateral
Face,forehead,orperiorbitalarea
Nature
Variesfromdiffuseachetotight,
pressing,constrictingpain
Throbbingmaybe
precededbyanaura
Pressurebehindeyesorfacedull,
bilateralpainworseinthemorning
Onset
Gradual
Sudden
Simultaneouswithsinussymptoms,
includingpurulentnasaldischarge
Duration
Minutestodays
Hoursto2days
Days(resolveswithsinussymptoms)
Non
headache
symptoms
Scalptenderness
Nausea
Nasalcongestion
Episodictensiontypeheadachesoftenrespondwelltononprescriptionanalgesics,includingacetaminophen,NSAIDs,
andsalicylates,especiallywhentakenatonsetoftheheadache.Ifnonprescriptionanalgesicsareusedtotreatchronic
headache,frequencyofuseshouldbelimitedtolessthan3daysperweektopreventmedicationoveruseheadache.
Whenmedicationoveruseheadacheissuspected,theuseofoffendingagent(s)shouldbetaperedandsubsequently
eliminated.Mostoften,taperingofanagentshouldbedonewithmedicalsupervisionbecauseuseofprescription
therapiesmaybeneededtocombattheincreasedheadachesthattemporarilyensueduringthedaystoweeksofthe
withdrawalperiod.10 Inadditiontononprescriptionorprescriptionmedication,chronictensiontypeheadachesmay
benefitfromphysicaltherapyandrelaxationexercises.Figure51outlinestheselftreatmentofheadachesandlists
exclusionsforselftreatment.
Amedicaldiagnosisofmigraineheadacheisrequiredbeforeselftreatmentcanberecommended.TakinganNSAID
orsalicylateattheonsetofsymptomscanabortmildormoderatemigraineheadache.Onceamigrainehasevolved,
analgesicsarelesseffective.Patientswithmigraineswhocanpredicttheoccurrenceoftheheadache(e.g.,during
menstruation)shouldtakeananalgesic(usuallyanNSAID)beforeoccurrenceoftheeventknowntotriggerthe
headache,aswellasthroughoutthedurationoftheevent.Forpatientswithcoexistingtensionandmigraineheadaches,
treatmentoftheinitiatingheadachetypecanabortthemixedheadache.
Sinusheadachesrespondwelltodecongestants(e.g.,pseudoephedrineorphenylephrine),whichareusefulforsinus
drainage(seeChapter11).Concomitantuseofdecongestantsandnonprescriptionanalgesicscanrelievesinus
headachepain.
NonpharmacologicTherapy
Chronictensiontypeheadachesmayrespondtorelaxationexercisesandphysicaltherapythatemphasizesstretching
andstrengtheningofheadandneckmuscles.Generaltreatmentmeasuresformigraineincludemaintainingregular
sleeping,eating,andexerciseschedules,stressmanagement,biofeedback,andcognitivetherapy.7 Somepatients
benefitfromapplyingiceorcoldpackscombinedwithpressuretotheforeheadortempleareastoreducepain
associatedwithacutemigraineattacks.
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Selfcareofheadache.Key:CHF=CongestiveheartfailureGI=gastrointestinalHBP=highbloodpressureNSAID=nonsteroidal
antiinflammatorydrugOTC=overthecounter.
Nutritionalstrategiesareintendedtopreventmigraineandarebasedon(1)dietaryrestrictionoffoodsthatcontain
triggers,(2)avoidanceofhungerandlowbloodglucose(atriggerofmigraine),and(3)magnesiumsupplementation.
Advocatesofnutritionaltherapyrecommendavoidingknownfoodallergiesandfoodswithvasoactivesubstances,such
asnitritestyramine(foundinredwineandagedcheese)phenylalanine(foundintheartificialsweeteneraspartame)
monosodiumglutamate(oftenfoundinAsianfood)caffeineandtheobromines(foundinchocolate).
PharmacologicTherapy
Availablenonprescriptionanalgesicsformanagementofheadacheincludeacetaminophen,NSAIDs(ibuprofenand
naproxen),andsalicylates(aspirinandmagnesiumsalicylate).Selectionofananalgesicshouldbebasedonacareful
reviewofapatientsmedicalandmedicationhistories.Medicalmanagementofnauseaaccompanyingmigraine
headachealsomaybeindicatedtoimprovesymptomaticreliefandfacilitatemedicationdeliverybytheoralroute.
Acetaminophen
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Acetaminophenisaneffectiveanalgesicandantipyretic.Acetaminophenproducesanalgesiathroughcentralinhibition
ofprostaglandinsynthesis.
Acetaminophenisrapidlyabsorbedfromthegastrointestinal(GI)tractandextensivelymetabolizedinthelivertoinactive
glucuronicandsulfuricacidconjugates.AcetaminophenisalsometabolizedbythecytochromeP450enzymesystemto
ahepatotoxicintermediatemetabolitethatisdetoxifiedbyglutathione.Whengivenbysuppository,rectalbioavailability
ofacetaminophenisapproximately50%60%ofthatachievedwithoraladministration.Onsetofanalgesicactivityof
acetaminophenisabout30minutesafteroraladministration.Durationofactivityisabout4hoursandisincreasedto68
hourswithanextendedreleaseformulation.
FDAapprovedusesfornonprescriptionacetaminophenincludereducingfeverandrelievingmildmoderatepain.Itis
effectiveinrelievingmildmoderatepainofnonvisceralorigin(i.e.,painthatisnotorganrelated).Randomized,double
blindstudieshavedocumentedtheeffectivenessofacetaminophen1000mgcomparedtoplaceboinpatientswith
migraineandtensiontypeheadache.12
RecommendedchildrenandadultdosagesofacetaminophenareprovidedinTables52and53.Table52provides
morestringentnonprescriptionacetaminophendosingforchildrenyoungerthan12yearsold.Table54listsselected
tradenameproducts.Acetaminophenisavailableforadministrationinvariousoralandrectaldosageforms.
Recentchangesimplementedtodecreasepediatricdosingerrorswithliquidacetaminophenformulationsinclude
havingonlyoneconcentration(160mL/5mL)availableforallchildrenyoungerthan12years.13 Acetaminophenoral
capsulescontaintastelessgranulesthatcanbeemptiedontoaspooncontainingasmallamountofcoldbeverage(hot
beveragesresultinabittertaste)orsoftfood.Capsulecontentsshouldnotbeaddedtoacupofliquidbecauselarge
numbersofgranulesmayadheretothecup.
Acetaminophenispotentiallyhepatotoxicindosesexceeding4g/day,especiallywithchronicuse.Patientsshouldbe
cautionedagainstexceedingthedoselimit.Moreconservativedosing(i.e.,2g/day)oravoidancemaybewarrantedin
patientsatincreasedriskforacetaminopheninducedhepatotoxicity,includingthosewithdiagnosedliverdisease,
concurrentuseofotherpotentiallyhepatotoxicdrugs,poornutritionalintake,oringestionofthreeormorealcoholic
drinksperday.14 Onealcoholicdrinkisdefinedas12ouncesofbeer,5ouncesofwine,or1.5ounces80proofliquor.
In2011,FDAmandatedplacementofaboxedwarningonacetaminophenproductsindicatingthatmorethan4g/day
maycausesevereliverdamage.Atthattime,FDArecommendedreductionofacetaminophenmaximumdailydosageof
39004000mgto30003250mgineffortstoreducetheriskofaccidentaloverdose.ThemanufacturerofTylenol
respondedtotheagencyssuggestionandvolunteeredtoreducetheirmaximumdailydosageforRegularStrength
Tylenolto3250mg(10tablets)andExtraStrengthTylenolto3000mg(6tablets).However,mostgenericmanufacturers
continuedtofollowthemandatedmaximumdailydosageof4g/day.Severalacetaminophen650mgproducts(tablets
andsuppositories)areavailablewithlabelingthatincludesamaximumdailydosageof3900mg(6doses).15 InJanuary
2014,FDAurgedhealthcareprofessionalstonolongerprescribeordispenseprescriptionproductscontainingmore
than325mgacetaminophenperdosageunit.Theagencyalsostatedthatitintended,inthenearfuture,toinstitute
proceedingstowithdrawapprovalofprescriptioncombinationdrugproductscontaining>325mgofacetaminophenper
dosageunitthatremainonthemarket.16
Acetaminophenpoisoningisamajorreasonforcontactingpoisoncontrolcentersandtheleadingcauseofacuteliver
failureintheUnitedStates.17 Hepatotoxicityfromacetaminophenisprobablydoserelatedandisuncommonat
recommendeddoses.18 Unintendedchronicoverdosecomprisesabouthalfofthecasesofacetaminopheninduced
acuteliverfailure.Contributingfactorsincluderepeateddosinginexcessofpackagelabeling,useofmorethanone
productcontainingacetaminophen,andalcoholingestion.19
TABLE52FDAApprovedDosagesforNonprescriptionAnalgesicsinChildrenYoungerthan12Yearsa
Ibuprofen(mg)DosebyBodyWeight(mg/kg) Acetaminophen(mg)
Age(years) Weight(lb)
510mg/kg
1015mg/kg
Aspirin(mg)
1015mg/kg
<2
<24
Askadoctora
Askadoctora
Askadoctora
23
2435
100
160
160
45
3647
150
240
240
68
4859
200
320
320
910
6071
250
400
400
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11
7295
300
480
480
a OTClabelinglimitsusetochildrenoverage3.Forpatientsseekingdosingadviceforyoungerchildren,weightbased
dosingisrecommended.
TABLE53RecommendedDosagesofNonprescriptionAnalgesicsforAdultsandChildren12YearsandOlder
Agent
DosageForms
UsualAdultDosage
(maximumdaily
dosage)
Acetaminophena,b Immediaterelease,extendedrelease,effervescent,disintegrating,
rapidrelease,andchewabletabletscapsulesliquiddropselixir
suspensionsuppositories
3251000mgevery46
hours(suggested3250
Ibuprofen
Immediatereleaseandchewabletabletscapsulessuspension
liquiddrops
200400mgevery46
hours(1200mg)
Naproxensodium
Tablets
220mgevery812hours
(660mg)
Overage65years:220
mgevery12hours(440
mg)
Aspirin
Immediaterelease,buffered,entericcoated,filmcoated,effervescent,
andchewabletabletssuppositories
6501000mgevery46
hours(4000mg)
Magnesium
salicylate
Tablets
650mgevery4hoursor
1000mgevery6hours
(4000mg)
mga )
a Themanufacturersvoluntarydosingreductionsin2011resultedinthefollowingdosageExtraStrengthTylenol:2
tablets(500mgeach)every6hourswithamaximumdailydosageof3000mg(6tablets).Themaximumdailydosagefor
RegularStrengthTylenolwasreducedto3250mg.However,amaximumdailydosageof4000mgisallowedfor
acetaminophenlabeling.15
b InJanuary2014,FDAurgedhealthcareprofessionalstonolongerprescribeordispenseprescriptionproducts
containing>325mgacetaminophenperdosageunit.Theagencyalsostatedthatitintended,inthenearfuture,to
instituteproceedingstowithdrawapprovalofprescriptioncombinationdrugproductscontaining>325mgof
acetaminophenperdosageunitthatremainonthemarket.16
Earlysymptomsofacetaminophenintoxicationcanincludenausea,vomiting,drowsiness,confusion,andabdominal
pain,butthesesymptomsmaybeabsent,belyingthepotentialseverityoftheexposure.Seriousclinicalmanifestationsof
hepatotoxicitybegin24daysafteracuteingestionofacetaminophenandincludeincreasedplasmaaspartate
aminotransferase(AST)andalanineaminotransferase(ALT)increasedplasmabilirubinwithjaundiceprolonged
prothrombintimeandobtundation.Inthemajorityofcases,hepaticdamageisreversibleoveraperiodofweeksor
months,butmoreseverecasesmayrequirelivertransplantorresultinfatalhepaticnecrosis.
TABLE54SelectedSingleEntityNonprescriptionAcetaminophenProducts
TradeName
AcetaminophenContent
PediatricFormulations
ChildrensTylenolMeltawayTablets
80mg
FeverAllInfantsSuppositories
80mg
FeverAllChildrensSuppositories
120mg
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FeverAllJuniorStrengthSuppositories
325mg
JrTylenolMeltawayTablets
160mg
ChildrensTylenolOralSuspension
160mg/5mL
InfantsTylenolOralSuspension
160mg/5mL
AdultFormulations
TylenolArthritisPainExtendedReleaseCaplets 650mg
Tylenol8hourExtendedReleaseCaplets
650mg
TylenolExtraStrengthCaplets
500mg
TylenolRapidBlastLiquid
500mg/15mL
TylenolRegularStrengthTablets
325mg
Becauseofthepotentialseriousnessofacetaminophenoverdose,allcasesshouldbereferredtoapoisoncontrolcenter
oremergencydepartment.Supportivecareisprovidedalongwithactivatedcharcoaltoreduceacetaminophen
absorptioninpatientswhopresentwithin1hourafteringestion.Whenacetaminophenserumlevels,relatedtotimesince
ingestion,exceedthoseknowntocausehepaticinjury,promptadministrationofacetylcysteineiswarrantedto
supplementglutathione,whichisessentialfordeactivationofatoxicintermediatemetaboliteofacetaminophen.
Acetylcysteineseffectivenessdecreasesifitisadministeredmorethan8hoursafteracuteingestion.Forpatientswith
chronicingestionsofgreaterthan4g/day,administrationofacetylcysteineisindicateduntillivertoxicityisruledoutby
assessmentofliverfunctiontests.
AsymptomaticelevationsinserumALThavebeenreportedinotherwisehealthyindividualstakingacetaminophen4
g/day.Inaprospectivestudy,39%ofpatientsexperiencedALTelevationsgreaterthanthreetimestheupperlimitof
normal.Theseelevationsgenerallyappearedinthefirstweekofuse,withsomeresolutiondespitecontinueddosing.
Theclinicalsignificanceofthisobservationisuncertain.20
Patientswithglucose6phosphatedehydrogenasedeficiency,ahereditarydiseasethatcausesprematurebreakdownof
redbloodcells,shouldusecautionwhentakingacetaminophen.Patientswithhypersensitivitytoacetaminophenare
contraindicatedforfutureuse.
Rarebutseriouscutaneousadversereactions(SCAR)havebeenfoundtobeassociatedwithuseofacetaminophenas
wellasotheranalgesicsincludingNSAIDs.Skinreactionsmayoccurineitherneworongoingusersofthedrugand
havethepotentialtoprogressintolifethreateningrashsuchasStevensJohnsonsyndromeandtoxicepidermal
necrolysis.Althoughtheseeventsareveryrare,itisimportanttobeawareofthepossibilityandreferpatientsforfurther
evaluation.21
ClinicallyimportantdruginteractionsofacetaminophenarelistedinTable55.Forpatientstakingwarfarin,
acetaminophenisconsideredtheanalgesicofchoicehowever,ithasbeenassociatedwithincreasesininternational
normalizedratio(INR).Regularacetaminophenuseshouldbediscouragedinpatientsonwarfarin.Patientswhorequire
higherscheduleddoses(e.g.,thosewithosteoarthritis)shouldhavetheirINRmonitoredandwarfarinadjustedas
acetaminophendosesaretitrated.
TABLE55ClinicallyImportantDrugDrugInteractionswithNonprescriptionAnalgesicAgents
Analgesic/Antipyretic
Drug
PotentialInteraction
Management/PreventiveMeasures
Acetaminophen
Alcohol
Increasedriskof
hepatotoxicity
Avoidconcurrentuseifpossible
minimizealcoholintakewhenusing
acetaminophen.
Acetaminophen
Warfarin
Increasedriskofbleeding
(elevationsinINR)
Limitacetaminophentooccasionaluse
monitorINRforseveralweekswhen
acetaminophen24gramsdailyisadded
ordiscontinuedinpatientsonwarfarin.
Aspirin
Valproicacid
Displacementfromprotein
Avoidconcurrentuseusenaproxen
bindingsitesandinhibition
insteadofaspirin(nointeraction).
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ofvalproicacidmetabolism
Aspirin
NSAIDs,including
COX2inhibitors
Increasedriskof
gastroduodenalulcersand
bleeding
Avoidconcurrentuseifpossibleconsider
useofgastroprotectiveagents(e.g.,
PPIs).
Ibuprofen
Aspirin
Decreasedantiplatelet
effectofaspirin
Aspirinshouldbetakenatleast30
minutesbeforeor8hoursafteribuprofen.
Useacetaminophen(orotheranalgesic)
insteadofibuprofen.
Ibuprofen
Phenytoin
Displacementfromprotein
bindingsites
Monitorfreephenytoinlevelsadjustdose
asindicated.
NSAIDs(several)
Bisphosphonates
IncreasedriskofGIor
esophagealulceration
Usecautionwithconcomitantuse.
NSAIDs(several)
Digoxin
Renalclearanceofdigoxin
inhibited
Monitordigoxinlevelsadjustdoseas
indicated.
Salicylatesand
NSAIDs(several)
Antihypertensive
agents,beta
blockers,ACE
inhibitors,
vasodilators,
diuretics
Antihypertensiveeffect
inhibitedpossible
hyperkalemiawith
potassiumsparingdiuretics
andACEinhibitors
Monitorbloodpressure,cardiacfunction,
andpotassiumlevels.
Salicylatesand
NSAIDs
Anticoagulants
Increasedriskofbleeding,
especiallyGI
Avoidconcurrentuse,ifpossibleriskis
lowestwithsalsalateandcholine
magnesiumtrisalicylate.
Salicylatesand
NSAIDs
Alcohol
IncreasedriskofGI
bleeding
Avoidconcurrentuse,ifpossible
minimizealcoholintakewhenusing
salicylatesandNSAIDs.
Salicylatesand
NSAIDs(several)
Methotrexate
Decreasedmethotrexate
clearance
AvoidsalicylatesandNSAIDswithhigh
dosemethotrexatetherapymonitorlevels
withconcurrenttreatment.
Salicylates(moderate
highdoses)
Sulfonylureas
Increasedriskof
hypoglycemia
Avoidconcurrentuse,ifpossiblemonitor
bloodglucoselevelswhenchanging
salicylatedose.
Key:ACE=AngiotensinconvertingenzymeCOX=cyclooxygenaseGI=gastrointestinalINR=international
normalizedratioNSAID=nonsteroidalantiinflammatorydrugPPI=proteinpumpinhibitor.
NonsteroidalAntiInflammatoryDrugs
NSAIDsrelievepainthroughcentralandperipheralinhibitionofcyclooxygenase(COX)andsubsequentinhibitionof
prostaglandinsynthesis.
AllnonprescriptionNSAIDsarerapidlyabsorbedfromtheGItractwithconsistentlyhighbioavailability.Theyare
extensivelymetabolized,mainlybyglucuronidation,toinactivecompoundsintheliver.Eliminationoccursprimarily
throughthekidneys.Onsetofactivityfornaproxensodiumandstandardibuprofenisabout30minutes.Ibuprofensodium
dehydrateisabsorbedmorerapidlyandhasaslightlyshorteronsetofactionthanthatofstandardibuprofen.Durationof
activityfornaproxensodiumisupto12hoursand68hoursforibuprofen.FDAapprovedusesfornonprescription
NSAIDsincludereducingfeverandrelievingminorpainassociatedwithheadache,thecommoncold,toothache,muscle
ache,backache,arthritis,andmenstrualcramps.NSAIDshaveanalgesic,antipyretic,andantiinflammatoryactivity,and
theyareusefulinmanagingmildmoderatepainofnonvisceralorigin.Naproxensodiumandibuprofenbecame
availablefornonprescriptionusein1994and1984,respectively,andbotharepropionicacidderivatives.AlthoughFDA
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approvedketoprofenfornonprescriptionuse,nocommerciallyavailablenonprescriptionanalgesicscurrentlycontain
thisagent.
RecommendedchildrenandadultdosagesofnonprescriptionNSAIDsareprovidedinTables52and53.Table56
listsselectedtradenameproducts.Unfortunately,liquidformulationsofibuprofenhavethesamepediatricdosingerrors
mentionedearlierforacetaminophen,butnochangeshavebeenimplementedtomitigatethedosingerrorsfor
ibuprofen.Adoseeffectrelationshiphasbeendemonstratedforibuprofenanalgesiaintherangeof100400mg.
NSAIDoverdosesusuallyproduceminimalsymptomsoftoxicityandarerarelyfatal.Inaprospectivestudyof329cases
ofibuprofenoverdose,43%ofibuprofenoverdosepatientswereasymptomatic.Amongpatientswithsymptoms,GIand
centralnervoussystem(CNS)symptomsweremostcommon(in42%and30%ofpatients,respectively)andincluded
nausea,vomiting,abdominalpain,lethargy,stupor,coma,nystagmus,dizziness,andlightheadedness.Hypotension,
bradycardia,tachycardia,dyspnea,andpainfulbreathingwerealsoreported.22
TABLE56SelectedSingleEntityNonprescriptionNonsteroidalAntiInflammatoryDrugs
TradeName
PrimaryIngredients
PediatricFormulationsofIbuprofenProducts
ChildrensAdvilSuspension
Ibuprofen100mg/5mL
ChildrensMotrinSuspension
Ibuprofen100mg/5mL
InfantsMotrinConcentratedDrops
Ibuprofen50mg/1.25mL
JuniorStrengthMotrinChewableTablets
Ibuprofen100mg
AdultFormulationsofIbuprofenProducts
AdvilMigraineSolubilizedCapsules
Ibuprofen200mg
AdvilTablets/Caplets/GelCaplets/FilmCoatedTabletsa Ibuprofen200mg
MotrinIBTablets/Caplets
Ibuprofen200mg
NaproxenProducts
AleveTablets/Caplets/LiquidGels/GelCaps
Naproxensodium220mg
MidolExtendedReliefCaplets
Naproxensodium220mg
a Providedas256mgofibuprofensodium.
ThemostfrequentadverseeffectsofNSAIDsinvolvetheGItractandincludedyspepsia,heartburn,nausea,anorexia,
andepigastricpain,evenamongchildrenusingpediatricformulations.NSAIDsmaybetakenwithfood,milk,orantacids
ifupsetstomachoccurs.Tabletsshouldbetakenwithafullglassofwater,suspensionsshouldbeshakenthoroughly,
andentericcoatedorsustainedreleasepreparationsshouldbeneithercrushednorchewed.Otheradverseeffects
includedizziness,fatigue,headache,andnervousness.Rashesoritching,photosensitivity,andfluidretentionoredema
mayoccurinsomepatientshowever,atnormaldoses,theseeffectsareusuallyrare.
GIulceration,perforation,andbleedingareuncommonbutseriouscomplicationsofNSAIDuse.Riskfactorsincludeage
olderthan60years,priorulcerdiseaseforGIbleeding,concurrentuseofanticoagulants(includingaspirin),higherdose
orlongerdurationoftreatment,andmoderateuseofalcohol.PackagelabelingforNSAIDsincludeswarningsabout
stomachbleedingwithadultdoses(seetheboxAWordaboutNSAIDsandStomachBleeding).23
AWordAboutNSAIDsandStomachBleeding
In2010,FDAapprovedalabelwarningconcerningstomachbleedingfornonprescriptionproductsthatcontainNSAIDs
inadultdoses:
Stomachbleedingwarning:ThisproductcontainsanNSAID,whichmaycauseseverestomachbleeding.Thechanceis
higherifyou:
Areage60orolder.
Havehadstomachulcersorbleedingproblems.
Takeabloodthinning(anticoagulant)orsteroiddrug.
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TakeotherdrugscontainingprescriptionornonprescriptionNSAIDs(aspirin,ibuprofen,naproxen,orothers).
Have3ormorealcoholicdrinkseverydaywhileusingthisproduct.
Takemoreorforalongertimethandirected.
Askadoctorbeforeuseifthestomachbleedingwarningappliestoyou:
Youhaveahistoryofstomachproblems,suchasheartburn.
Youhavehighbloodpressure,heartdisease,livercirrhosis,orkidneydisease.
Youaretakingadiuretic.
Stopuseandaskadoctorif:
Youexperienceanyofthefollowingsignsofstomachbleeding:
Feelfaint.
Vomitblood.
Havebloodyorblackstools.34
Havestomachpainthatdoesnotgetbetter.
NSAIDsareassociatedwithincreasedriskformyocardialinfarction,heartfailure,hypertension,andstroke.The
mechanismbywhichtheriskisconferredisnotclear,butitmayberelatedtoincreasedthromboxaneA2activityand
suppressedvascularprostacyclinsynthesis,resultinginvasoconstrictionandplateletaggregation.Accordingtoresults
fromametaanalysisofrandomizedtrials,thecardiovascularriskofnonselectiveNSAIDsappearstodependondose
andduration.Inaddition,theriskdiffersbetweenindividualnonselectiveNSAIDs.Forinstance,ibuprofenhasbeen
associatedwithasignificantincreaseincardiovascularrisk,whereasnaproxenhasnotthus,naproxenisconsidered
thepreferred,saferoption.24
TheAmericanHeartAssociationrecommendsthatpatientswithorathighriskforcardiovasculardisease(e.g.,
hyperlipidemia,hypertension,diabetes,orothermacrovasculardisease)avoidNSAIDs.Lowriskpatientsshould
exercisecautioninusingNSAIDsbytakingtheminimumdosefortheshortestdurationneededtocontrolsymptoms.
ClinicalevidencehasshownthattheuseofNSAIDsinpatientswhohaveapasthistoryofmyocardialinfarctionwill
increasetheirriskoffuturecardiovasculareventsindefinitely.25
ClinicallyimportantdrugdruginteractionsofNSAIDsarelistedinTable55.Ibuprofenincreasesbleedingtimeby
reversiblyinhibitingplateletaggregation.Patientstakingaspirinforcardiovascularprophylaxisshouldtakeitatleast1
hourbeforeor8hoursafteribuprofentoavoidapharmacodynamicinteractionthatinhibitstheantiplateleteffectof
aspirin.Indosesof12002400mg/day,ibuprofendoesnotappeartoaffecttheINRinpatientstakingwarfarin.However,
ibuprofenshouldnotberecommendedforselftreatmentinpatientswhoareconcurrentlytakinganticoagulantsbecause
itsantiplateletactivitycouldincreaseGIbleeding.
PatientswhoingestthreeormorealcoholicdrinksperdayshouldbecautionedabouttheincreasedriskofadverseGI
events,includingstomachbleeding.Theyalsoshouldbereferredtotheirprimarycareproviderformonitoringoftheir
NSAIDuse.
NSAIDsmaydecreaserenalbloodflowandglomerularfiltrationrateasaresultofinhibitionofrenalprostaglandin
synthesis.Consequently,increasedbloodureanitrogenandserumcreatininevaluescanoccur,oftenwithconcomitant
sodiumandwaterretention.Advancedage,hypertension,diabetes,atheroscleroticcardiovasculardisease,anduseof
diureticsappeartoincreasetheriskofrenaltoxicitywithibuprofenuse.Therefore,patientswithahistoryofimpaired
renalfunction,congestiveheartfailure,ordiseasesthatcompromiserenalhemodynamicsshouldnotselfmedicatewith
NSAIDs.
Salicylates
SalicylatesinhibitprostaglandinsynthesisfromarachidonicacidbyinhibitingbothisoformsoftheCOXenzyme(COX1
andCOX2).Theresultingdecreaseinprostaglandinsreducesthesensitivityofpainreceptorstotheinitiationofpain
impulsesatsitesofinflammationandtrauma.Althoughsomeevidencesuggeststhataspirinalsoproducesanalgesia
throughacentralmechanism,itssiteofactionisprimarilyperipheral.
Salicylatesareabsorbedbypassivediffusionofthenonionizeddruginthestomachandsmallintestine.Factorsaffecting
absorptionincludedosageform,gastricpH,gastricemptyingtime,dissolutionrate,andthepresenceofantacidsorfood.
Absorptionfromimmediatereleaseaspirinproductsiscomplete.Rectalabsorptionofasalicylatesuppositoryisslow
andunreliable,aswellasproportionaltorectalretentiontime.
Onceabsorbed,aspirinishydrolyzedintheplasmatosalicylicacidin12hours.Salicylicacidiswidelydistributedtoall
tissuesandfluidsinthebody,includingtheCNS,breastmilk,andfetaltissue.Proteinbindingisconcentration
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dependent.Atconcentrationslowerthan100mg/mL,approximately90%ofsalicylicacidisboundtoalbumin,whereas
atconcentrationsgreaterthan400mg/mL,approximately75%isbound.Salicylicacidislargelyeliminatedthroughthe
kidney.UrinepHdeterminestheamountofunchangeddrugthatiseliminated,withurinaryconcentrationsincreasing
substantiallyinmorealkalineurine(pH~8).
Dosageformalterationsincludeentericcoating,buffering,andsustainedrelease.Theseformulationsweredevelopedto
changetherateofabsorptionand/orreducethepotentialforGItoxicity.Entericcoatedaspirinisabsorbedonlyfromthe
smallintestineitsabsorptionismarkedlyslowedbyfood,whichisattributedtoprolongedgastricemptyingtime.
Hypochlorhydriafromacidsuppressingagents(especiallyprotonpumpinhibitors)mayresultindissolutionofenteric
coatedproductsinthestomach,negatinganypotentialbenefitonlocalgastrictoxicity.Forpatientsrequiringrapidpain
relief,entericcoatedaspirinisinappropriatebecauseofthedelayinabsorptionandthetimetoanalgesiceffect.
Bufferedaspirinproductsareavailableinbothtabletandeffervescentforms.Althoughbufferedproductsareabsorbed
morerapidlythanarenonbufferedproducts,timetoonsetofeffectisnotimprovedappreciably.Commonbuffersinclude
aluminumhydroxidemagnesiumcarbonate,hydroxide,oroxidecalciumcarbonateandsodiumbicarbonate(in
effervescentformulations).Someeffervescentaspirinsolutionscontainlargeamountsofsodiumandmustbeavoidedby
patientswhorequirerestrictedsodiumintake(e.g.,patientswithhypertension,heartfailure,orrenalfailure).Sustained
releaseaspirinisformulatedtoprolongdurationofactionbyslowingdissolutionandabsorption.Magnesiumsalicylateis
availableasatabletorcapsule.Sodiumsalicylateisapprovedfornonprescriptionuse,butitisnotcurrentlyavailablein
acommercialproduct.
FDAapprovedusesforsalicylatesincludetreatmentofsymptomsforosteoarthritis,rheumatoidarthritis,andother
rheumatologicdiseases,aswellastemporaryreliefofminorachesandpainsassociatedwithbackacheormuscle
aches.Salicylatesalsoareeffectiveintreatingmildmoderatepainfrommusculoskeletalconditionsandfever.Because
ofitsinhibitoryeffectsonplateletfunction,aspirinisalsoindicatedforpreventionofthromboembolicevents(e.g.,
myocardialinfarctionandstroke)inhighriskpatients.
RecommendedchildrenandadultdosagesofnonprescriptionsalicylatesareprovidedinTables52and53.Table57
providesselectedsalicylateproducts.Aspirindosagesrangingfrom46g/dayareusuallyneededtoproduceanti
inflammatoryeffects.Themaximumanalgesicdosageforselfmedicationwithaspirinis4g/daytherefore,anti
inflammatoryactivityoftenwillnotoccurunlessthedrugisusedatthehighendoftheacceptabledosagerange.
TABLE57SelectedAdultFormulationsofNonprescriptionSingleEntitySalicylateProducts
TradeName
PrimaryIngredients
BayerLowDoseAspirinTablets
Aspirin81mg
St.Joseph81mgChewableAspirin
Aspirin81mg
EcotrinRegularStrengthSafetyEntericCoatedTablets
Aspirin325mg
GenuineBayerAspirinTablets
Aspirin325mg
BayerPlusExtraStrength
Aspirin500mg
ExtraStrengthDoansCaplets
Magnesiumsalicylate580mg
PercogesicMaximumStrengthBackacheReliefCoatedCaplets Magnesiumsalicylatetetrahydrate580mg
Mildsalicylateintoxication(salicylism)occurswithchronictoxicbloodlevels,generallyachievedinadultswhotake90
100mg/kg/dayofasalicylateforatleast2days.Conditionsthatpredisposepatientstosalicylatetoxicityinclude
(1)markedrenalorhepaticimpairment(e.g.,uremia,cirrhosis,orhepatitis)(2)metabolicdisorders(e.g.,hypoxiaor
hypothyroidism)(3)unstabledisease(e.g.,cardiacarrhythmias,intractableepilepsy,orpoorlycontrolleddiabetes)(4)
statusasthmaticusand(5)multiplecomorbidities.Symptomsincludeheadache,dizziness,tinnitus,difficultyhearing,
dimnessofvision,mentalconfusion,lassitude,drowsiness,sweating,thirst,hyperventilation,nausea,vomiting,and
occasionaldiarrhea.Thesesymptomscanallbereversedbyloweringtheplasmaconcentrationtoatherapeuticrange.
Tinnitus,typicallyoneoftheearlysignsoftoxicity,shouldnotbeusedasasoleindicatorofsalicylatetoxicity.
Acutesalicylateintoxicationiscategorizedasmild(ingestionof<150mg/kg),moderate(ingestionof150300mg/kg),or
severe(ingestionof>300mg/kg).Symptomsdependontheconcentrationandincludelethargy,nausea,vomiting,
dehydration,tinnitus,hemorrhage,tachypneaandpulmonaryedema,convulsions,andcoma.Acidbasedisturbances
areprominentandrangefromrespiratoryalkalosistometabolicacidosis.Initially,salicylateaffectstherespiratorycenter
inthemedulla,producinghyperventilationandrespiratoryalkalosis.Inseverelyintoxicatedadultsandinmostsalicylate
poisonedchildrenyoungerthan5years,respiratoryalkalosisprogressesrapidlytometabolicacidosis.Childrenare
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morepronethanareadultstodevelophighfeverinsalicylatepoisoning.Hypoglycemiaresultingfromincreasedglucose
utilizationmaybeespeciallyseriousinchildren.BleedingmayoccurfromtheGItractormucosalsurfaces,and
petechiaeareaprominentfeatureatautopsy.
EmergencymanagementofacutesalicylateintoxicationisdirectedtowardpreventingabsorptionofsalicylatefromtheGI
tractandprovidingsupportivecare.Activatedcharcoalshouldbeusedathomeonlyifrecommendedbypoisoncontrol
centeroremergencydepartmentpersonnel.Inanemergencydepartmentsetting,gastrointestinaldecontaminationwith
gastriclavageoractivatedcharcoalmaybeundertaken.Enhancingrenaleliminationcanbeaccomplishedthrough
alkalinizationoftheurine.DosingrecommendationsfortheuseofactivatedcharcoalareincludedinChapter20.
Aspirinisknowntocommonlycausedyspepsia,whichmaybeminimizedbytakingitwithfood.Inaddition,aspirinis
associatedwithgastritisandulcerationoftheupperGItract.ItproducesGImucosaldamagebypenetratingthe
protectivemucousandbicarbonatelayersofthegastricmucosaandpermittingbackdiffusionofacid,therebycausing
cellularandvascularerosion.Twodistinctmechanismscausethisproblem:(1)alocalirritanteffectresultingfromthe
medicationcontactingthegastricmucosaand(2)asystemiceffectfromprostaglandininhibition.Lackofupper
abdominalpainordiscomfortisnotareliableindicatorfortheabsenceofgastrointestinaldamageassociatedwithuseof
aspirinorotherNSAIDs.26
TheuseofaspirinhasbeenshowntoincreasetheriskforseriousupperGIeventstwotofourfold.26 Itisrecommended
thatthelowesteffectivedosebeusedforcardioprotection(usually81mg)andthattheuseofprotonpumpinhibitorsmay
beindicatedforgastricprotection.26 PatientswithriskfactorsforupperGIbleedingshouldavoidselftreatmentwith
aspirin.Theseriskfactorsinclude(1)historyofuncomplicatedorbleedingpepticulcer(2)ageolderthan60years(3)
concomitantuseofaspirinorotherNSAIDs,anticoagulants,antiplateletagents,bisphosphonates,selectiveserotonin
reuptakeinhibitors,orsystemiccorticosteroids(4)infectionwithHelicobacterpylori(5)rheumatoidarthritis(6)NSAID
relateddyspepsiaand(7)concomitantuseofalcohol.27
VariousaspirinformulationsmayhavedifferentratesofGIsideeffects.Entericcoatingmaydecreaselocalgastric
irritation.However,withregardtotheriskofmajorGIulcerationandbleeding,nodifferencehasbeenidentifiedamong
plain,entericcoated,andbufferedproducts.
Seriousaspirinintoleranceisuncommonandconsistsoftwotypes:cutaneous(urticariaandangioedema)orrespiratory
(bronchospasm,laryngospasm,andrhinorrhea).Themechanismisnotimmunologicallymediated.Riskfactorsfor
seriousaspirinintoleranceincludechronicurticaria(forthecutaneoustype)andasthmawithnasalpolyps(forthe
respiratorytype).Tenpercentofpeoplediagnosedwithasthmahaveaspirinsensitivity.28 Severityoftheintoleranceis
variable,rangingfromminortosevere.Patientswithaspirinintolerancegenerallyareadvisedtoavoidaspirinandother
NSAIDs.However,thenonacetylatedsalicylates(magnesiumsalicylate)areconsideredsafe,andacetaminophenwill
notcausecrosssensitivity.28
Nonprescriptionsalicylatesinteractwithseveralotherimportantdrugsanddrugclasses.Clinicallyimportantdrug
interactionsofsalicylatesarelistedinTable55.Whenmonitoringtherapyinpatientswhoaretakinghighdose
salicylates,healthcareprovidersshouldreviewcurrentdruginteractionreferencesfornewlyidentifiedinteractions.
Aspiriningestionmayproducepositiveresultsonfecaloccultbloodtestingtherefore,itsuseshouldbediscontinuedfor
atleast3daysbeforetesting.Similarly,aspirinshouldbediscontinued27daysbeforesurgeryandshouldnotbeused
torelievepainaftertonsillectomy,dentalextraction,orothersurgicalprocedures,exceptundertheclosesupervisionofa
healthcareprovider.AspirincanpotentiatebleedingfromcapillarysitessuchasthosefoundintheGItract,tonsillar
beds,andtoothsockets.
Becauseoftheeffectonhemostasis,aspiriniscontraindicatedinpatientswithhypoprothrombinemia,vitaminK
deficiency,hemophilia,historyofanybleedingdisorder,orhistoryofpepticulcerdisease.Patientswithcompromised
renalfunctionhavethepotentialfordecreasedrenalexcretionofmagnesium,allowingaccumulationoftoxiclevelswhen
takingmagnesiumsalicylate.Themaximum24hourdoseofmagnesiumsalicylatecontains264mg(11mEq)of
magnesium.
Allsalicylatesshouldbeavoidedinpatientswithahistoryofgoutorhyperuricemiabecauseofdoserelatedeffectson
renaluricacidhandling.Dosagesof12g/dayinhibittubularuricacidsecretionwithoutaffectingreabsorptionandmay
increaseplasmauricacidlevels,whichcanprecipitateorworsenagoutattack.Moderatedosagesof23g/dayhave
littleeffectonuricacidsecretion.Morethan5g/daymaydecreaseplasmauricacidbyincreasingitsrenalexcretion,but
becausethesesalicylatedosesaretoxic,theyshouldnotbeusedintheclinicalmanagementofgoutorhyperuricemia.
Reyessyndromeisanacuteillnessoccurringalmostexclusivelyinchildren15yearsofageoryounger.Thecauseis
unknown,butviralandtoxicagents,especiallysalicylates,havebeenassociatedwiththesyndrome.Onsetusually
followsaviralinfectionwithinfluenza(typeAorB)orvaricellazoster(chickenpox).Reyessyndromeischaracterizedby
progressiveneurologicdamage,fattyliverwithencephalopathy,andhypoglycemia.Themortalityratemaybeashighas
50%.
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TheAmericanAcademyofPediatrics,FDA,theCentersforDiseaseControlandPrevention,andtheSurgeonGeneral
haveissuedwarningsthataspirinandothersalicylates(includingbismuthsubsalicylateandnonaspirinsalicylates)
shouldbeavoidedinchildrenandteenagerswhohaveinfluenzaorchickenpox.Thefollowingcontraindicationislisted
onlabelsofnonprescriptionaspirinandaspirincontainingproducts:
Aspirinshouldnotbeusedinchildrenandteenagersforviralinfections,withorwithoutfever,because
oftheriskofReyessyndromewithconcomitantuseofaspirinincertainviralillnesses.
Althoughasimpleviralupperrespiratoryinfection(e.g.,acommoncold)isnotacontraindicationtoaspirinuse,itcanbe
difficulttodifferentiatesymptomsofthistypeofinfectionfromthoseofinfluenzaandchickenpox.Manyhealthcare
providers,therefore,recommendaconservativeapproachofavoidingaspirinwheneversymptomsresemblingthoseof
influenzaarepresent.TheuseofaspirinasapediatricantipyretichasallbutceasedintheUnitedStates,ashave
reportsofReyessyndrome.
FDArequiresawarninglabelregardingalcoholuseonallnonprescriptionanalgesic/antipyreticproductsforadultuse.
ConcurrentuseofaspirinwithalcoholincreasestheriskofadverseGIevents,includingstomachbleeding.Patientswho
consumethreeormorealcoholicdrinksdailyshouldbecounseledabouttherisksandreferredtotheirprimarycare
providerbeforeusingaspirin.
CombinationProducts
Manynonprescriptionanalgesicsareavailableincombinationproducts(Table58).
Caffeineisusedasanadjuncttoanalgesicsfortensiontypeandmigraineheadaches.Italsomayhaveitsown
analgesicpropertiesandisknowntocausewithdrawalheadachewhentakenregularly.Combinationdosageforms
containingadecongestantandeitheracetaminophenoranNSAIDarealsoavailable.Thesecombinationsappear
logicalforuseinsinusheadachesorotherindicationsforwhichbothanalgesiaanddecongestionareneeded.
TABLE58SelectedNonprescriptionCombinationAnalgesicProducts
TradeName
PrimaryIngredients
AcetaminophenContainingProducts
ExcedrinTensionHeadache
Acetaminophen500mgcaffeine65mg
ExcedrinPM
Acetaminophen500mg38mg
ExcedrinSinus
Acetaminophen325mgphenylephrine5mg
GoodysPMPowder
Acetaminophen500mgdiphenhydramine38mg
PercogesicOriginalStrength
Acetaminophen325mgdiphenhydramine12.5mg
PercogesicExtraStrength
Acetaminophen500mgdiphenhydramine12.5mg
SudafedPEPressure+Pain
TylenolPM
Acetaminophen500mgdiphenhydramine25mg
TylenolSinusCongestionandPain
NSAIDContainingProducts
AdvilCold&Sinus
Ibuprofen200mgpseudoephedrine30mg
AdvilCongestionRelief
Ibuprofen200mgphenylephrine10mg
AleveDSinus&Headache
Naproxensodium220mgpseudoephedrine120mg
MotrinPM
Naproxensodium200mgdiphenhydramine38mg
Sudafed12hPressure+Pain
Naproxensodium220mgpseudoephedrine120mg
AspirinContainingProducts
AnacinMaximumStrength
Aspirin500mgcaffeine32mg
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AnacinRegularStrength
BayerCafiaspirina
ExcedrinExtraStrengthorExcedrinMigraine
Aspirin250mgacetaminophen250mgcaffeine65mg
GoodysCoolOrangePowder
Aspirin500mgacetaminophen325mgcaffeine65mg
GoodysExtraStrengthHeadachePowder
Aspirin500mgacetaminophen260mgcaffeine32.5mg
GoodysExtraStrengthorGoodysMigraineReliefcaps Aspirin250mgacetaminophen250mgcaffeine65mg
Key:NSAID=Nonsteroidalantiinflammatory.
Enhancedanalgesiahasbeenreportedforvariousantihistamine/analgesiccombinations,including
orphenadrine/acetaminophenandphenyltoloxamine/acetaminophen.Althoughthesecombinationshavedemonstrated
superiorefficacyinacutepain,comparedwithacetaminophenalone,theiruseislimitedbythesedatingeffectsofthe
antihistamines.
PharmacotherapeuticComparison
AspirinversusNonacetylatedSalicylates
Althoughdefinitiveclinicaldataarelacking,aspirinandnonacetylatedsalicylatesarebelievedtobeequalinanti
inflammatorypotencyhowever,aspirinisthoughttobeasuperioranalgesicandantipyretic.
AspirinversusAcetaminophen
Numerouscontrolledstudieshavedemonstratedtheequivalentanalgesicefficacyofaspirinandacetaminophenona
milligramformilligrambasishowever,statisticalmethodsusedtocompareeffectivenessbetweendifferentstudies
showthatacetaminophenmaynotbequiteaseffectiveinsometypesofpain.29
AspirinversusNSAID
Ibuprofenhasbeenshowntobeatleastaseffectiveasaspirinintreatingvarioustypesofpain,includingdental
extractionpain,dysmenorrhea,andepisiotomypain.Becauseaspirinmustbedosedneartheselfcaremaximumto
achieveantiinflammatoryeffects,NSAIDsmaybepreferredforselftreatmentofinflammatorydisorderssuchas
rheumatoidarthritisoracutemuscleinjury.29
NSAIDversusAcetaminophen
Forepisodictensiontypeheadache,acetaminophen1000mgappearstoprovidereliefthatisequivalenttonaproxen
375mg.30 Formoderateseveredentalorsorethroatpaininchildren,singledosesofacetaminophen715mg/kg
producedpainreliefsimilartothatofibuprofen410mg/kg.Ibuprofenwasamoreeffectiveantipyretic,andbothdrugs
werewelltolerated.31 Areviewofevidencecomparingibuprofenwithacetaminophenforheadachetreatmentinchildren
andadultsfoundthatonlytwotrialshadshownamodestadvantageforibuprofen,andtheresearchersconcludedthat
thetwoagentsshouldbeconsideredequallyeffective.32 Acetaminophendoesnothaveantiinflammatoryproperties,
whichmaylimititseffectivenessinsomeconditions,includingdysmenorrhea.29
NaproxenversusIbuprofen
Naproxensodium220mgandibuprofen200mgappeartohavesimilarefficacy.Theonsetofactivityalsoissimilar
betweenthetwoNSAIDs.Durationofactionofnaproxenissomewhatlongerthanthatofibuprofen,buttheclinical
significanceofthisdifferenceisnotclear.Nonetheless,somepatientsreportbetterresponsetooneNSAIDthanto
anotherforreasonsthatareunclear.
ProductSelectionGuidelines
SpecialPopulationConsiderations
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Ageisanimportantconsiderationintheselectionofanappropriatenonprescriptionmedicationforselftreatmentof
headache.Parentsofchildrenyoungerthan8yearsshouldconsultapediatricianpriortogivingtheirchildren
nonprescriptionmedications.Children2yearsandoldermayuseacetaminophenoribuprofen.Children12yearsand
oldermayusenaproxen.TodecreasetheriskofReyessyndrome,parentsshouldnotuseaspirinoraspirincontaining
productsinchildrenages15yearsoryounger,unlessdirectedtodosobyaprimarycareprovider.
OlderadultsareatincreasedriskformanyadverseeffectsofsalicylatesandNSAIDs.Comorbidities,impairedrenal
function,anduseofothermedicationscontributetotheincreasedrisk.OlderadultsaremorevulnerabletoseriousGI
toxicity,hypertensive,andrenaleffectsofsalicylatesandNSAIDs.33 Forthisreason,acetaminophenisgenerally
recognizedasthetreatmentofchoiceformanagementofmildmoderatepaininolderadults.
Whenaspirinseffectonhemostasisisaconcernandperipheralantiinflammatoryactivityisnotneeded,acetaminophen
isanappropriateanalgesicforselfmedication.Alternatively,ifaperipheralantiinflammatoryagentisindicated,
prescriptionsalicylatecompounds(e.g.,salsalateandcholinemagnesiumtrisalicylate)arereasonablealternatives.
Acetaminophencrossestheplacentabutitisconsideredsafeforuseduringpregnancy(FDApregnancycategoryB).
Acetaminophenappearsinbreastmilk,producingamilktomaternalplasmaratioof0.5:1.0.A1grammaternaldose
hasanestimatedmaximuminfantdosethatis1.85%ofthematernaldose.Theonlyadverseeffectreportedininfants
exposedtoacetaminophenthroughbreastmilkisararelyoccurringmaculopapularrash,whichsubsidesupondrug
discontinuation.Acetaminophenuseisconsideredcompatiblewithbreastfeeding.
NoevidenceexiststhatNSAIDsareteratogenicineitherhumansoranimals.However,useoftheseagentsis
contraindicatedduringthethirdtrimesterofpregnancybecauseallpotentprostaglandinsynthesisinhibitorscancause
delayedparturition,prolongedlabor,andincreasedpostpartumbleeding.Ibuprofenandnaproxenarepregnancy
categoriesBandC,respectively,inthefirsttrimesterandpregnancycategoryDinthethirdtrimester.Theseagentsalso
canhaveadversefetalcardiovasculareffects(e.g.,prematureclosureoftheductusarteriosus).Lactatingwomentaking
upto2.4gramsofibuprofenperdayshowednomeasurableexcretionofibuprofenintobreastmilktherefore,ibuprofen
isconsideredcompatiblewithbreastfeeding.Naproxenalsoisconsideredcompatiblewithbreastfeeding.
Aspirinshouldbeavoidedduringpregnancy,especiallyduringthelasttrimester,andduringbreastfeeding.Aspirinis
pregnancycategoryDduringthelasttrimesteritsingestionduringpregnancymayproducematernaladverseeffects,
suchasanemia,antepartumorpostpartumhemorrhage,andprolongedgestationandlabor.Regularaspiriningestion
duringpregnancymayincreasetheriskforcomplicateddeliveries,includingunplannedcesareansection,breech
delivery,orforcepsdelivery.However,definitivedatasupportingthisconcernarelacking.
Aspirinreadilycrossestheplacentaandcanbefoundinhigherconcentrationsintheneonatethaninthemother.
Salicylateeliminationisslowinneonatesbecauseoftheliversimmaturityandunderdevelopedcapacitytoformglycine
andglucuronicacidconjugatesandbecauseofreducedurinaryexcretionresultingfromlowglomerularfiltrationrates.
Fetaleffectsfrominuteroaspirinexposureincludeintrauterinegrowthretardation,congenitalsalicylateintoxication,
decreasedalbuminbindingcapacity,andincreasedperinatalmortality.Inuteromortalityresults,inpart,fromantepartum
hemorrhageorprematureclosureoftheductusarteriosus.Inuteroaspirinexposurewithin1weekofdeliverycan
produceneonatalhemorrhagicepisodesand/orpruriticrash.Reportedneonatalbleedingcomplicationsinclude
petechiae,hematuria,cephalhematoma,subconjunctivalhemorrhage,andbleedingaftercircumcision.Anincreased
incidenceofintracranialhemorrhageinprematureorlowbirthweightinfantsassociatedwithmaternalaspirinusenear
thetimeofbirthalsohasbeenreported.34 Anassociationbetweenmaternalaspiriningestion,oralclefts,andcongenital
heartdiseasehasbeenreported.However,therelationshipbetweenmaternalaspiriningestionandcongenital
malformationremainsunresolved,andstudieshavefailedtoconfirmarelationshipbetweenmaternalingestionof
aspirinandincreasedriskforfetalmalformation.
Aspirinandothersalicylatesareexcretedintobreastmilkinlowconcentrations.Aftersingledoseoralsalicylate
ingestion,peakmilklevelsoccuratabout3hours,producingamilktomaternalplasmaratioof3:8.Althoughnoadverse
effectsonplateletfunctioninnursinginfantsexposedtoaspirinviabreastmilkhavebeenreported,theseagentsstill
mustbeconsideredapotentialrisk.34
Patientswithrenalimpairmentshouldexercisecautionwhenusingsalicylates.Clinicallyimportantalterationsinrenal
bloodflowresultinginacutereductioninrenalfunctioncanresultfromuseofevenshortcoursesofsalicylates.Renally
impairedpatientsshouldbereferredformedicalevaluationforassistanceinselectingananalgesic.
PatientFactors
Nonprescriptionanalgesicsareavailableinanumberofdosageforms.Duringpatientassessment,healthcareproviders
shoulddeterminewhichdosageformwillprovideanoptimumoutcomeforthepatient.Ifrapidresponseisdesired,then
immediatereleaseoraldosageformswouldbepreferredovercoatedorextendedreleaseforms.Forpatients
experiencingmigraineheadachewithseverenausea,rectaldosageformsmaybepreferred.Liquiddosageformsoften
areusedinchildrenoradultpatientswhohavedifficultyswallowingsoliddosageforms.
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Useofacetaminopheninthepediatricpopulationiscomplicatedbythevariousavailablestrengthsandformulations.
Unintendedoverorunderdosingcanoccurwhenparentsswitchbetweeninfantdrops(80mg/0.8mL)andelixir(160
mg/5mL),incorrectlyassumingthattheyarethesameconcentration.
OtherissueswithpediatricdosesofacetaminophenwerediscussedatajointmeetingoftheNonprescriptionDrugs
AdvisoryCommitteeandthePediatricAdvisoryCommitteethecommitteesrecommended(1)asingleconcentrationfor
soliddose,singleingredientacetaminophenproductsforchildren,(2)theadditionofweightbaseddosingforchildren
ages212,and(3)theadditionofnewlabeldirectionsforchildrenages6monthsto2yearsthatwouldincludethe
indicationforfeverreduction.
Inaddition,rapidlygrowinginfantsquicklyoutgrowpreviousdoserequirements.Therefore,recalculationofthepediatric
doseaccordingtopresentageandbodyweightisrecommendedatthetimeofeachtreatmentcourse.
Patientswithsignificantalcoholingestion(threeormoredrinksperday)shouldavoidselftreatmentwithnonprescription
analgesics.
Patientswhoareintoleranttoaspirinalsomaycrossreactwithotherchemicalsordrugs.Upto15%ofpatientswhoare
intoleranttoaspirinmaycrossreactwhenexposedtotartrazine(FoodDrugandCosmeticYellowDyeNo.5),whichcan
befoundinmanydrugsandfoods.Amongthosewiththerespiratorytypeofaspirinsensitivity,therateofcrossreaction
betweenaspirinandacetaminophen,ibuprofen,andnaproxenindocumentedaspirinintolerantpatientsis7%,98%,
and100%,respectively.34 HighcrossreactionratesalsoarereportedwithsomeprescriptionNSAIDs.Theproposed
mechanismofcrosssensitivitybetweenaspirinandNSAIDsinvolvesshuntingarachidonicmetabolismdownthe
lipoxygenasepathway(becauseofinhibitionoftheCOX1enzymepathway),resultinginaccumulationofleukotrienes
thatcancausebronchospasmandanaphylaxis.Acetaminophenandnonacetylatedsalicylatesareweakinhibitorsof
COX1atmoderatedoses.Therefore,patientswithahistoryofaspirinintoleranceshouldbeadvisedtoavoidallaspirin
andNSAIDcontainingproducts,andtouseacetaminophenoranonacetylatedsalicylate,withthecaveatthat
acetaminophendoesnotofferantiinflammatoryproperties.
PatientPreferences
Considerationofdosingfrequencyinproductselectionmayimproveoutcomesforindividualpatients.Naproxencanbe
taken23timesdailyandmayimprovepatientadherence.Conversely,acetaminophen,ibuprofen,andsalicylatesmay
requiredosingasfrequentlyasevery4hours.Becauseofthedelayedabsorptionofsustainedreleaseaspirin,this
dosageformisnotusefulforrapidpainreliefbutmaybeusefulasabedtimemedication.
ComplementaryTherapies
Butterbur,feverfew,riboflavin,andcoenzymeQ10commonlyareusedforthepreventionofmigraineheadachesandare
discussedindepthinChapter51.Thesenaturalproductsaregenerallyineffectiveforthetreatmentofheadaches.Other
unprovenremediesincludepeppermintoilappliedtotheforeheadandtemplesfortreatmentoftensionheadache,
magnesiumfortreatmentandpreventionofmigraine,andriboflavinforpreventionofmigraineheadache.
Acupuncturehasbeenusedtopreventmigraineandtensiontypeheadache.Evaluationofacupunctureiscomplicated
bydifficultiesinblindinganddifferencesinidentifyingacupuncturepoints.Overall,resultshavebeenvariable,but
severalrandomized,placebocontrolledtrialsfoundacupunctureeffectiveinreducingfrequencyandseverityof
headache.35
AssessmentofHeadache:ACaseBasedApproach
Beforeselftreatmentofheadachecanberecommended,thehealthcareprovidermustassessthepatientsheadache
astotype,severity,location,frequency,intensityovertime,andageatonset.Thenextstepistoobtainamedicaland
psychosocialhistory.Allcurrentmedicationsshouldbeinventoried,andallpastandpresentheadachetreatments
shouldbereviewed,withemphasisondeterminingwhichtreatments,ifany,weresuccessfulorpreferred.
Secondaryheadaches,otherthanminorsinusheadache,areexcludedfromselftreatment.Headacheassociatedwith
seizures,confusion,drowsiness,orcognitiveimpairmentmaybeasignofbraintumor,ischemicstroke,subdural
hematoma,orsubarachnoidhemorrhage.Headacheaccompaniedbynausea,vomiting,fever,andstiffneckmay
indicatebrainabscessormeningitis.Headachewithnightsweats,achingjoints,fever,weightloss,andvisualsymptoms
(e.g.,blurring)inpatientswithrheumatoidarthritismayindicatecranialarteritis.Headacheassociatedwithlocalized
facialpain,muscletenderness,andlimitedmotionofthejawmayindicatetemporomandibularjointdisorder.
Cases51and52illustrateassessmentofapatientwithheadache.
PatientCounselingforHeadache
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Tooptimizeoutcomesfromtherapy,theprovidershouldinstructpatientstotakeanappropriatedoseofanalgesicearlyin
thecourseoftheheadache.Theuseofnonprescriptionanalgesicstopreemptorabortmigraineheadachesalsoshould
beexplainedtopatientswithmigraineswhoseheadachesarepredictable.Patientswhohaveheadacheswithsome
frequencyshouldbeencouragedtokeepalogoftheirheadachestodocumenttriggers,frequency,intensity,durationof
episodes,andresponsetotreatment.Thisrecordalsomaybehelpfulinidentifyingfactorsthatcanimproveheadache
preventionandtreatment.Patientsshouldbeadvisedthatcontinuingorescalatingpaincanbeasignofamoreserious
problemandthatpromptmedicalattentioniswarranted.Appropriatedrugandnondrugmeasuresfortreatingheadaches
shouldbeexplainedtothepatient.Frequentuseofnonprescriptionanalgesicsisnotappropriatebecauseoftheriskfor
medicationoveruseheadache.Providersshouldconveythemessagethatnonprescriptionanalgesicsarepotent
medicationswithaccompanyingpotentialadverseeffects,interactions,andprecautions/warnings.TheboxPatient
EducationforHeadachelistsspecificinformationtoprovidepatients.
Case51
RelevantEvaluationCriteria
Scenario/ModelOutcome
InformationGathering
1.Gatheressentialinformationabout
thepatientssymptomsandmedical
history,including:
a.descriptionofsymptom(s)(i.e.,
nature,onset,duration,severity,
associatedsymptoms)
Patientstatesthatasevereheadachetookplaceyesterdayandincapacitated
himforalmost8hours.Thepaineventuallysubsided,butnothinghecoulddo
wouldmakeitstop.Thistypeofheadachehashappenedseveraltimesinthe
past2months.
b.descriptionofanyfactorsthatseem Brightlightandloudsoundsmadethepainworse.Evenslightmovementsof
toprecipitate,exacerbate,and/or
hisheadresultedindiscomfort.
relievethepatientssymptom(s)
c.descriptionofthepatientseffortsto
relievethesymptoms
Hestatesthattheonlythinghecoulddowastoliedownonhisbedwiththe
curtainsdrawnandthedoorshut.Acetaminophenhasnotbeenhelping.
d.patientsidentity
DomRugolo
e.age,sex,height,andweight
26yearsold,male,6ft1in.,245lb
f.patientsoccupation
Producemanageratagrocerystore
g.patientsdietaryhabits
Heeatshealthysomeofthetimebutdoeslikefruitsandvegetables.He
sometimeshasdifficultyeatingregularly.Heskipsbreakfastalotbecauseof
hisbusyscheduleandofteneatsfrozendinnersbecausetheyarequickand
easy.
h.patientssleephabits
Hehasnoproblemssleeping.Becauseofthenatureofhiswork,hehastobe
upat5ammostdays,buthetriestocompensatefortheearlyrisingbygoing
tobedatadecenthour.
i.concurrentmedicalconditions,
Hehasmildacneonhisfacethatiscurrentlybeingtreatedwithtretinoincream
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prescriptionandnonprescription
medications,anddietary
supplements
0.025%appliedtopicallydaily.
j.allergies
Bactrimcausedabadrashafewyearsago.
k.historyofotheradversereactions
tomedications
None
l.other(describe)_______
Hedoesnotsmokebutdoesdrinkinfrequentlywithfriends(1or2beersevery
fewweeks).
AssessmentandTriage
2.Differentiatepatients
signs/symptomsandcorrectlyidentify
thepatientsprimaryproblem(s)
(Table51).
Mr.Rugolomightbehavingmigraineheadachesasindicatedbyintensepain
thatisexacerbatedbybrightlights,sounds,andheadmovement.
3.Identifyexclusionsforself
treatment(Figure51).
Undiagnosedmigraineisanexclusionforselftreatment.
4.Formulateacomprehensivelistof
therapeuticalternativesforthe
primaryproblemtodetermineiftriage
toamedicalpractitionerisrequired,
andsharethisinformationwiththe
patientorcaregiver.
Optionsinclude:
(1)ReferMr.Rugolotoanappropriatehealthcareprovider.
(2)Recommendselfcarewithanonprescriptionanalgesic.
(3)RecommendselfcareuntilMr.Rugolocanseeanappropriatehealthcare
provider.
(4)Takenoaction.
Plan
5.Selectanoptimaltherapeutic
alternativetoaddressthepatients
problem,takingintoaccountpatient
preferences.
ReferraltoahealthcareproviderisappropriateforMr.Rugolo.Hemayneeda
prescriptiononlytherapythatisspecificformigraines.Untilahealthcare
providercanbeseen,thepatientshouldtakeibuprofen200mgevery46
hours.Thedosagecanbeincreasedto400mgifnecessarybutislimitedto
6tabletsperday.Thepatientshouldtakethemedicationassoonashefeels
theheadachebegin.
6.Describetherecommended
therapeuticapproachtothepatientor
caregiver.
Whatyouhavebeenexperiencingmaybemigraineheadaches.Itis
recommendedthatyouseekevaluationbyyourprimarycareproviderto
determineappropriatetreatment.Takeibuprofenattheonsetofheadacheuntil
youcanseeyourhealthcareprovider.
7.Explaintothepatientorcaregiver
therationaleforselectingthe
recommendedtherapeuticapproach
fromtheconsideredtherapeutic
alternatives.
Ibuprofenmaybeagoodalternativetotheacetaminophenyouweretaking
becauseitisinadifferentclassofmedicationandexertsitstherapeuticaction
inadifferentmanner.Themostbenefitwillbeseeniftheibuprofenistakenat
theearliestsignofheadache,ratherthanwaitingforthepaintobecome
severe.
PatientEducation
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8.Whenrecommendingselfcare
withnonprescriptionmedications
and/ornondrugtherapy,convey
accurateinformationtothepatientor
caregiver:
a.appropriatedoseandfrequencyof
administration
Takeibuprofen200mg,1tabletevery46hours.Thisdosagemaybe
increasedto400mg(2tablets)every46hoursifneeded.Donotexceed
6tabletsina24hourperiod.
b.maximumnumberofdaysthe
therapyshouldbeemployed
Usethismedicationonlyuntilyouareabletoseeyourhealthcareprovider.
Selfcareforaheadacheshouldnotexceed10days.Also,limittreatmentto
3daysperweek.
c.productadministrationprocedures
Startibuprofenatthefirstsignofheadache.
d.expectedtimetoonsetofrelief
Reliefshouldbeginin3060minutes.
e.degreeofreliefthatcanbe
reasonablyexpected
Completeresolutionofyoursymptomsisunlikely.Forthisreason,youwill
needtoseeyourhealthcareprovider.
f.mostcommonsideeffects
Stomachupset.Takingibuprofenwithfoodmayhelppreventthat.
g.sideeffectsthatwarrantmedical
interventionshouldtheyoccur
Ibuprofenshouldbestoppedifthereisseverestomachpain,bloodyvomit,
blackstool,abnormalbruisingorbleeding,orallergicreaction(swellingofthe
faceorthroat,difficultybreathing).
h.patientoptionsintheeventthat
conditionworsensorpersists
Followupwiththehealthcareprovider.
i.productstoragerequirements
Storeibuprofeninaclosedcontaineratroomtemperatureawayfrommoisture
andchildren.
j.Specificnondrugmeasures
Keeptrackofeventspriortotheheadachestotryanddeterminepossible
triggers.
Solicitfollowupquestionsfromthe
patientorcaregiver.
Arethereeffectivetreatmentsfortheseheadachesthatmydoctorcangive
me?Idontwanttokeephavingmylifedisruptedbythem.
Answerthepatientsorcaregivers
questions.
Multipleprescriptionmedicationsformigraineheadachesthathave
establishedsafetyandefficacyareavailable.Yourhealthcareproviderwill
determinetheappropriatecourseoftreatmenttohelpyouminimizetheeffects
thattheheadacheshaveonyourlife.
EvaluationofPatientOutcome
9.Assesspatientoutcome.
Callthepatientinafewdaystodeterminewhetherheisreceivingfurther
medicalcare.
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Case52
RelevantEvaluationCriteria
Scenario/ModelOutcome
InformationGathering
1.Gatheressentialinformationabout
thepatientssymptomsandmedical
history,including:
a.descriptionofsymptom(s)(i.e.,
nature,onset,duration,severity,
associatedsymptoms)
Patientstatesthatshehashadtwomildheadachesinthepastfewweeks.
Bothtimesthepainwentfromthetoptothebaseofherhead.Thepain
lastedonlyafewhoursandwentawaybyitself,butitwassignificant
enoughtopreventherfromgettingherworkdoneforclass.Shewantsto
planaheadforthenextheadachesoshedoesnothavetosacrificestudy
time.
b.descriptionofanyfactorsthatseemto Theheadacheshavebeenhappeningbeforeexamswhenherstressisat
precipitate,exacerbate,and/orrelieve
itspeak.
thepatientssymptom(s)
c.descriptionofthepatientseffortsto
relievethesymptoms
Shestatesthatshestoppedfocusingonherworkandrelaxeduntilshefell
asleep.
d.patientsidentity
MartaSchuler
e.age,sex,height,andweight
22yearsold,female,5ft8in.,130lb
f.patientsoccupation
Fulltimestudent
g.patientsdietaryhabits
Shetriestoeathealthybutisoftenontherunandskipsbreakfastfrequently.
Forlunchsheusuallygrabsabagelandteafromthecafeteria.Dinneris
usuallyawraporasalad,andshesnacksoncashewsthroughouttheday.
h.patientssleephabits
Shetriestogotobedbymidnightbecauseshehasclassat8am.She
sometimesstaysuplatestudying,butthathappensinfrequentlyandusually
doesnotdisrupthernormalsleeppattern.
i.concurrentmedicalconditions,
prescriptionandnonprescription
medications,anddietarysupplements
Shehasmildasthmaforwhichshehasanemergencyinhalerthatshehas
notneededinmonths.
j.allergies
None
k.historyofotheradversereactionsto
medications
None
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l.other(describe)_______
Ms.Schulerdrinkssociallyontheweekendandsaysthatshehasacouple
ofdrinkstounwind.Shedoesnotsmoke.
AssessmentandTriage
2.Differentiatepatients
signs/symptomsandcorrectlyidentify
thepatientsprimaryproblem(s)(Table
51).
Ms.Schulerishavingatensionheadachethatismostlikelyduetothe
stressofschool.
3.Identifyexclusionsforselftreatment
(Figure51).
Ms.Schulerhasnoexclusionsforselftreatment.
4.Formulateacomprehensivelistof
therapeuticalternativesfortheprimary
problemtodetermineiftriagetoa
medicalpractitionerisrequired,and
sharethisinformationwiththepatientor
caregiver.
Optionsinclude:
(1)ReferMs.Schulertoanappropriatehealthcareprovider.
(2)Recommendselfcarewithanonprescriptionanalgesic.
(3)RecommendselfcareuntilMs.Schulercanseeanappropriatehealth
careprovider.
(4)Takenoaction.
Plan
5.Selectanoptimaltherapeutic
alternativetoaddressthepatients
problem,takingintoaccountpatient
preferences.
Ms.Schulershoulduseanonprescriptionanalgesictohelprelieveher
headachepain.Acetaminophenisanappropriatemedicationforshortterm
treatmentforhersymptoms.
6.Describetherecommended
therapeuticapproachtothepatientor
caregiver.
Whatyouhavebeenexperiencingmaybetensionheadaches.Itislikelya
resultofthestressyouareexperiencingfromschool.Takingacetaminophen
willhelptorelievethesymptoms.
7.Explaintothepatientorcaregiverthe
rationaleforselectingthe
recommendedtherapeuticapproach
fromtheconsideredtherapeutic
alternatives.
Whentakenasdirected,acetaminophencanprovidequickreliefof
headachesymptomsandhasalowerchanceofgastrointestinalsideeffects
comparedwithNSAIDs.
PatientEducation
8.Whenrecommendingselfcarewith
nonprescriptionmedicationsand/or
nondrugtherapy,conveyaccurate
informationtothepatientorcaregiver:
a.appropriatedoseandfrequencyof
administration
Takeacetaminophen500mg,1tabletevery6hours.Thisdosagemaybe
increasedto2tabletsevery6hours,ifneeded.Donottakemorethan6
tablets(3000mg)ina24hourperiod.Notethatmanynonprescriptionand
prescriptionproductsincludeacetaminophen,soavoidtakingmorethan
oneproductcontainingacetaminophen.
b.maximumnumberofdaysthetherapy Taketheacetaminophenfornomorethan10days.Also,limitfuture
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shouldbeemployed
treatmentto3daysperweek.
c.productadministrationprocedures
Startacetaminophenwhenyoufeelaheadachestarting.Takethe
medicationwithafullglassofwater.
d.expectedtimetoonsetofrelief
Reliefshouldbeginin3060minutes.
e.degreeofreliefthatcanbe
reasonablyexpected
Completeresolutionofyoursymptomsispossible.
f.mostcommonsideeffects
Nauseaandvomitingarethemostcommonsideeffects.
g.sideeffectsthatwarrantmedical
interventionshouldtheyoccur
Acetaminophenshouldbestoppedifyouexperienceyellowingoftheskin
oreyes,bloodyvomit,blackstool,abnormalbruisingorbleeding,orallergic
reaction(hives,swellingoftheface,difficultybreathing).
h.patientoptionsintheeventthat
conditionworsensorpersists
Ifacetaminophendoesnotrelieveyourheadache,youalsomaytrya
nonsteroidalantiinflammatorydrugsuchasibuprofenornaproxen.
Otherwise,seekadvicefromyourhealthcareprovider.
i.productstoragerequirements
Storeacetaminopheninaclosedcontaineratroomtemperatureawayfrom
moistureandchildren.
j.Specificnondrugmeasures
Managingyourstressmayhelpyouavoidtensionheadaches.Relaxation
exercisescanhelpwithstressmanagement.
Solicitfollowupquestionsfromthe
patientorcaregiver.
CanIconsumealcoholwiththismedication?
Answerthepatientsorcaregivers
questions.
Consumingalcoholwhiletakingacetaminophenshouldbeavoided.The
combinationcanincreasetheriskofliverdamage.
EvaluationofPatientOutcome
9.Assesspatientoutcome.
Toevaluateefficacyofthetreatment,advisepatienttocallthepharmacy
afterusingtherecommendedmedication.
EvaluationofPatientOutcomesforHeadache
Appropriatefollowupwilldependonheadachefrequencyandseverity,aswellaspatientfactors.Forpatientswith
episodicheadaches,atrialof612weeksmaybeneededtoassessefficacyoftreatment.Forchronicheadache,follow
upafter46weeksshouldbeadequatetoassesstreatmentefficacy.Forsevereheadaches,patientsshouldbe
contactedwithin10daysofinitiationofselftreatmenttoassessefficacyandtolerability.Inallcases,patientsshouldseek
medicalattentionifheadachespersistlongerthan10daysorworsendespiteselftreatment.
Onequarterofmigrainepatientswillbenefitfrompreventivetherapybutmanydonotreceiveit.36 Patientswithmigraine
headacheswhoarenotadequatelyselftreatedshouldbereferredforamedicalevaluationbecauseeffective
prescriptiontherapiesareavailabletosubstantiallylimitpainanddisability.
KeyPointsforHeadache
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Mosttensiontype,migraine,andsinusheadachesareamenabletotreatmentwithnonprescriptionmedications.
Patientswithsymptomssuggestiveofsecondaryheadaches(exceptforminorsinusheadache)orundiagnosed
migraineheadachesshouldbereferredformedicalattention.
Manypatientswithfrequentheadachesmayexperienceimprovementbyidentifyingandmodifying
environmental,behavioral,nutritional,orothertriggersfortheirheadaches.
Thechoiceofnonprescriptionanalgesicforanindividualpatientdependsonpatientpreferences,presenceof
precautionaryorcontraindicatingconditions,concomitantmedications,cost,andotherfactors.
Pharmacistshavebeenidentifiedaskeysourcesofinformationonnonprescriptionanalgesicstoreduceriskfor
acetaminopheninducedhepatotoxicityandNSAIDinducedGIbleeding,cardiovascularevents,and
nephrotoxicity.
Useofnonprescriptionanalgesicsforheadacheshouldbelimitedto3daysperweektopreventmedication
overuseheadache.
PatientEducationforHeadache
Theobjectivesofselftreatmentareto(1)relieveheadachepain,(2)preventheadacheswhenpossible,and(3)prevent
medicationoveruseheadachesbyavoidingchronicuseofnonprescriptionanalgesics.Carefullyfollowingproduct
instructionsandtheselfcaremeasureslistedherewillhelpensurethebestresults.
TensionTypeHeadaches
Nonprescriptionpainrelievers(analgesics)areusuallyeffectiveinrelievingtensiontypeheadaches.However,
consultyourprimaryproviderbeforeusingthemforchronictensiontypeheadachesthatoccurmorethan15days
permonthfor6months.
Ifnonprescriptionpainrelieversareusedforchronicheadaches,keeprecordsofhowoftentheyareused,and
sharethisinformationwithyourprovider.
MigraineHeadache
Avoidsubstances(food,caffeine,alcohol,andmedications)orsituations(stress,fatigue,oversleeping,fasting,
andmissingmeals)thatyouknowcantriggeramigraine.
Usethefollowingnutritionalstrategiestopreventmigraine:
Avoidfoodsorfoodadditivesknowntotriggermigraines,includingredwine,agedcheese,aspartame,
monosodiumglutamate,coffee,tea,colabeverages,andchocolate.
Avoidfoodstowhichyouareallergic.
Eatregularlytoavoidhungerandlowbloodsugar.
Considertakingmagnesiumsupplements.
Ifonsetofmigrainesispredictable(e.g.,headacheoccursduringmenstruation),takeaspirin,ibuprofen,or
naproxentopreventtheheadache.Starttakingtheanalgesic2daysbeforeyouexpecttheheadacheand
continueregularuseduringthetimetheheadachemightstart.
Trytostopamigrainebytakingaspirin,acetaminophen,oranonsteroidalantiinflammatoryagent(NSAID)atthe
onsetofheadachepain.
Ifdesired,useanicebagorcoldpackappliedwithpressuretotheforeheadortemplestoreducethepain
associatedwithacutemigraineattacks.
SinusHeadache
Considerusingacombinationofadecongestantandanonprescriptionanalgesictorelievethepainofsinus
headache.
PrecautionsforNonprescriptionAnalgesics
Ifyouarepregnantorbreastfeeding,consultyourprimarycareproviderbeforetakinganynonprescription
medications.
Ifyouhaveamedicalconditionoraretakingprescriptionmedications,obtainmedicaladvicebeforetakinganyof
thesemedications.Nonprescriptionanalgesicsareknowntointeractwithseveralmedications.
Donottakenonprescriptionanalgesicslongerthan10daysunlessamedicalproviderhasrecommended
prolongeduse.
Donottakethesemedicationsifyouconsumethreeormorealcoholicbeveragesdaily.
Donotexceedrecommendeddosages.
Productscontainingaspartameand/orphenylalanine(usuallychewabletablets)shouldnotbegivento
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individualswithphenylketonuria.
Salicylates(AspirinandMagnesiumSalicylate)andNSAIDs(IbuprofenandNaproxen)
Donottakeaspirinduringthelast3monthsofpregnancyunlessaprimarycareproviderissupervisingsuchuse.
Unsuperviseduseofthismedicationcouldharmtheunbornchildorcausecomplicationsduringdelivery.
Donotgiveaspirinorothersalicylatestochildren15yearsofageoryoungerwhoarerecoveringfrom
chickenpoxorinfluenza.ToavoidtheriskofReyessyndrome,ararebutpotentiallyfatalcondition,use
acetaminophenforpainrelief.
DonottakeaspirinorNSAIDsifyouareallergictoaspirinorhaveasthmaandnasalpolyps.Take
acetaminopheninstead.
DonottakeaspirinorNSAIDsifyouhavestomachproblemsorulcers,liverdisease,kidneydisease,orheart
failure.
DonottakeNSAIDsifyouhaveorareathighriskforheartdiseaseorstrokeunlesstheuseissupervisedbya
healthcareprovider.
Donottakeaspirinifyouhavegout,diabetesmellitus,orarthritisunlesstheuseissupervisedbyahealthcare
provider.
DonottakesalicylatesorNSAIDsifyouaretakinganticoagulants.
Donottakemagnesiumsalicylateifyouhavekidneydisease.
Donotgivenaproxentoachildyoungerthan12years.
WhentoSeekMedicalAttention
StoptakingsalicylatesorNSAIDsandseekmedicalattentionifanyofthefollowingsymptomsoccur:
Headache,dizziness,ringingintheears,difficultyinhearing,dimnessofvision,mentalconfusion,
lassitude,drowsiness,sweating,thirst,hyperventilation,nausea,vomiting,oroccasionaldiarrhea.These
symptomsindicatemildsalicylatetoxicity.
Dizziness,nauseaandmildstomachpain,constipation,ringingintheears,orswellinginthefeetorlegs.
ThesesymptomsarecommonsideeffectsofsalicylatesandNSAIDs.
Rashorhives,orred,peelingskinswellinginthefaceoraroundtheeyeswheezingortroublebreathing
bloodyorcloudyurineunexplainedbruisingandbleedingorsignsofstomachbleedingsuchasbloody
orblacktarrystools,severestomachpain,orbloodyvomit(seetheboxAWordaboutNSAIDsand
StomachBleeding).Thesesymptomsrequireimmediatemedicalattention.
Acetaminophen
Toavoidpossibledamagetotheliver,donottakemorethan4gramsofacetaminophenadayfromall
nonprescriptionandprescriptionsingleingredientorcombinationproductscontainingacetaminophen.
Donotdrinkalcoholwhiletakingthismedication.
Followdosageinstructionsforacetaminophencarefullyifyouhaveglucose6phosphatedehydrogenase
deficiency.
WhentoSeekMedicalAttention
Stoptakingacetaminophenandseekmedicalattentionifyoudevelopnausea,vomiting,drowsiness,confusion,
orabdominalpain.
References
1.StovnerLJ,HagenK,JensenR,et.al.Theglobalburdenofheadache:adocumentationofheadacheprevalenceand
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