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Diagnosis:OtitisExterna
1.WhatdrugtherapywouldyouprescribeforC.J.?Why?
Answer: Since C.J.’s TM is intact and he’s a teenager who may struggle with adherence, an
ototopicalfluoroquinolone,suchasofloxacin,isrecommendedaslongashehasmedicalinsurance
tocoverthecost. Prescribe ofloxacin withdirections toapply 10 drops intotheear canal once
daily for 10 days. In addition C.J. could use over-the-counter analgesics, such as ibuprofen or
acetaminophen,forpainrelief.
2.Whataretheparametersformonitoringsuccessofthetherapy?
Answer: C.J. should experience symptom improvement within 48 to 72 hours. He should be
instructedtocontacthishealthcareproviderifhisearpainandfullnessdon’timprovewithinthat
timeframe.Itmaytakeawholeweekforthesymptomstoresolve.
3.WhatlifestylechangeswouldyourecommendtoC.J.?
Answer:Heshouldavoidgettingwaterinhisearforuptooneweektoallowhiscurrentinfection
toresolve.Thereafter,sinceheisacompetitiveswimmer,hewillhavetoimplementsomelifestyle
changestopreventrecurrence.Oneconsiderationis todrytheearswithacoolhair dryertoaid
fluidremoval.Inaddition,discussC.J.’svaccinationhistorytodetermineifheisuptodatewithhis
vaccinesincludinghisinfluenzavaccinewheninseason.
CASESTUDY2
T.G.isa14-month-oldboybroughttohispediatrician’sofficebyhismother.Hewassenthomefrom
daycare the previous day with a fever of 101.4°F. He has rhinorrhea and congestion, and appears
irritable.Hismotherstatesthathewastuggingonhisleftearwhenshepickedhimupthedaybefore
andthathecouldnotsleepwellthatnight.Shegavehimadoseofibuprofenbeforebedbecausehe
“felthot.”Priortodaycaredropofyesterday,hewasnotedtohavemildnasalcongestionforthepast3
days,butinhisnormalbehavioranddidnotfeelwarm.Uponexaminationintheoffice,histemperature
is102.3°F,hischestisclear,andmildnasalcongestionisnoted.Examinationbyotoscopeidentifies
bilateralerythemaandbulging,immobiletympanicmembranes(TMs)(LearningObjectives1,2,and
3).
Diagnosis:AcuteOtitisMedia
1.DoyourecommenddrugtherapyforT.G.?Ifso,whatwouldyouprescribeandwhy?
Answer: Based on T.G.’s acute presentation of fever, bilateral AOM, and age less than 2, he
qualifiesforantibiotictreatment.Ifhedoesn’thaveahistoryofallergytopenicillins,thenahigh
doseofamoxicillinisrecommended,90mg/kg/ddividedin2dailydosesfora10-daycourse.Ifhe
hadahistoryofpenicillinallergy,thencefpodoximeoranotheroralthird-generationcephalosporin
wouldbeindicated.Inadditiontoantibiotics,over-the-counteranalgesicsshouldberecommended
forpainrelief.Counselthemothertocontinuegivingtheibuprofenathome(doublecheckherdose
is10mg/kg/dosePOnomoreoftenthanevery8hours).
2.Whataretheparametersformonitoringsuccessofthetherapy?
Answer:T.G.’ssymptomsshouldimprovein72hours.Ifnot,themothershouldcontactthehealth
careprovidersincethepatientmightbefailingtherapy.
3.WhatpreventativemeasuresareimplementedforT.G?
Answer:DiscussT.G.’svaccinationhistorytodetermineifheisuptodatewithhisvaccinesbased
onhisage,includinghisinfluenzavaccinewheninseason.Ifit’shisfirstinfluenzaseasonreceiving
thevaccine,hemayrequiretwodoses.ConsulttheAdvisoryCommitteeonImmunizationPractices
for the latest recommendations. By this age, T.G. should have completed the 13-valent
pneumococcalconjugatevaccineandH.influenzaetypeBseries.Althoughhemaybedueforthe
4thdoseofeachifthevaccinesweren’tadministeredathisone-yearwell-visitappointment.
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*Starredreferencesarecitedinthetext.
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children.NorthernCaliforniaKaiserPermanenteVaccineStudyCenterGroup.PediatricInfectiousDiseaseJournal,19(3),187-195.
*Boyce, T. G., & Balakrishnan, K. (2018). Otitis externa and necrotizing otitis externa. In S. Long (Ed.), Principles and practices of
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Surgery,19,341-347.
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UNIT
5
PharmacotherapyforCardiovascularDisorders
18
Hypertension
SamanthaLandolfaandDianeE.Hadley
LearningObjective
1.Diagnoseandclassifypatientswithhypertension.
2.Determineappropriatebloodpressuregoalsforspecificpatientpopulations.
3.Developanappropriatepatient-specifictreatmentregimen.
4.Educatepatientsonnonpharmacologicinterventionstotreathypertension.
INTRODUCTION
Hypertension(HTN)orhighbloodpressure(BP)isoneofthemostcommonchronicconditionsmanaged
byprimarycareprovidersandotherhealthpractitioners.Itincreasestheriskforcardiovasculardisease
(CVD) and chronic kidney disease (CKD). Approximately 45.6% of adults in the United States have
HTN. The average annual estimated directandindirect costs of HTN from 2014 to 2015 was $55.9
billion(Viranietal.,2020).HeartdiseaseisawidelyprevalentcauseofdeathintheUnitedStates,thus
makingmanagementofapatient’sBPcrucial.ThedeathrateattributabletoHTNincreased25.7%from
2007to2017,causingmorethan90,000deathsin2017.Despitethesealarmingnumbers,35.3%ofU.S.
adultswithHTNarenotawaretheyhaveHTNbecausethediseasecanbeasymptomatic;therefore,the
diseaseisappropriatelynicknamed“thesilentkiller.”
TheprevalenceofHTNcontinuestogrowduetotheincreasingageofourpopulation,obesity,andhigh
dietarysaltintake(Beckettet al.,2008). Theprevalenceof obesitywas38.3% amongadultsaged20
years and older, according to data from the2013 to 2016 National Health and Nutrition Examination
Survey.Obesity, impaired renal function, and diabetes mellitus are all associated with resistantHTN
(Vongpatanasin,2014).
HTNincreaseswithageandaffectsallethnicgroups.However,blackssufferdisproportionatelyfrom
HTN and its effects, leading to high rates of cardiovascular morbidity and mortality. HTN in blacks
occurs atanearlierage, ismore severe,andresults inorgan damage suchas coronaryheartdisease,
stroke,andend-stagerenaldiseasemoreoftenthanitdoesinwhites.HTNalsodisproportionatelyaffects
peoplewithlowersocioeconomicstatus.
CAUSES
HTNisclassifiedasprimary(essential),secondary,oridiopathicwhenthereisnoidentifiablecausefor
elevatedBP.Approximately95%ofadultswithHTNhaveprimaryoressentialHTN,andtheexactcause
ofprimaryHTNisnotknown.Environmental factors(excess salt,obesity,andsedentarylifestyle) and
geneticfactors(inappropriatelyhighactivityoftherenin—angiotensin—aldosteronesystem[RAAS]and
the sympathetic nervous system) are hypothesized contributing factors and are being studied. An
additionalcauseofHTNisstiffeningoftheaortaartery,secondarytoincreasingage.Thisisreferredto
asisolatedorpredominantsystolicHTN.Itischaracterizedbyhighsystolicbloodpressure(SBP)with
normaldiastolicbloodpressure(DBP)andisfoundprimarilyinolderadults.
SecondaryHTN,wherethecausecanbeidentified,accountsfor5%ofall casesofHTN.Themain
causesofsecondaryHTNareCKD(anemia,lowglomerularfiltrationrate,smallkidney),renovascular
HTN(abdominal bruit,elevated plasma reninactivity,>30%elevationofserumcreatinine[SCr] upon
initiation of BP-lowering agents), hypothyroidism (elevated thyroid-stimulating hormone),
hyperparathyroidism (elevated calcium), pheochromocytoma, sleep apnea, and primary aldosteronism
(hypokalemia,ratioserumaldosterone/plasmareninactivity>25:30).
Furthermore, medications can serve as a factor that may increase BP. Examples include oral
contraceptives,nicotine,steroids,appetitesuppressants,tricyclicantidepressants,venlafaxine(Effexor),
cyclosporine(Sandimmune),nonsteroidal antiinflammatorydrugs(NSAIDs),andsomenasal decongestants (which includeover-the-counter preparations). Herbal products thataffect BP includecapsicum,
goldenseal,licoriceroot,mahuang(Ephedra),Scotchbroom,witchhazel,andyohimbine.
PATHOPHYSIOLOGY
RoleoftheNervousSystem
The central and autonomic nervous systems play a key dual role in regulating BP. Centrally located
presynaptic beta receptors stimulate the release of norepinephrine, while alpha-2 receptors inhibit
norepinephrinerelease.ReceptorslocatedintheperipheryalsoregulateBP.Thesereceptorsarelocated
oneffectorcellsthatareinnervatedbysympatheticneurons.Stimulationofalpha-1receptorslocatedon
arteriolesandvenulescausesvasoconstriction,whileactivationofthebeta-2receptorsonthesevessels
producesvasodilation.Beta-1receptors,whicharelocatedintheheartandkidneys,regulateheartrate
andcontractility,whichultimatelyimpactscardiacoutput.BecauseBPistheproductofcardiacoutput
andperipheralresistance,anyreductionincardiacoutputresultsinadecreaseinBP.Therefore,blockade
ofbeta-1receptorsdecreasescardiacoutput,peripheralresistance,andBP.
Baroreceptors,whicharenerveendingslocatedinlargearteriessuchastheaorticarchandcarotids,
additionallyplayasignificantroleinregulatingBP.ThesereceptorsaresensitivetochangesinBP.When
BP drops drastically, the baroreceptors send an impulse to the brain stem, which results in
vasoconstriction and increased heart rate and contractility. In contrast, elevation in BP increases
baroreceptoractivity,whichresultsinvasodilationanddecreasedheartrateandcontractility.
PeripheralautoregulatorycomponentsalsoplayaroleincontrollingBP.Normally,risesinBPresultin
sodiumandwater eliminationbythekidney. Inturn,plasmavolume,cardiac output,andBPdecrease.
DysfunctionofthismechanismcanraiseplasmavolumeandBP.
RoleoftheRenalSystem
RAAS regulates sodium, potassium, and fluid balance in the body. Renin, an enzyme secreted by the
juxtaglome-rular cellsontheafferentarteriolesofthekidney, isreleasedinresponsetochangesinBP
caused by reduced renal perfusion, decreased intravascular volume, or increased circulation of
catecholamines. Renin catalyzes the conversion of angioten-sinogen to angiotensin I. Angiotensin I is
converted to the potent vasoconstrictor angiotensin II by angiotensin-converting enzyme (ACE).
AngiotensinIIcausesdirectvasoconstrictionandstimulationofthesympatheticnervoussystem.AngiotensinIIalso stimulatesreleaseofaldosteronefromtheadrenalgland,whichresultsintheretentionof
sodiumandwater.Innormalphysiology,angiotensinIIdirectlyinhibitsfurtherreleaseofreninthrougha
negative feedbacksystem. Ifthe negative feedbacksystem fails,BPrises. Hyperinsulinemiais another
contributingfactortoHTN,bycausingsodiumretentionandstimulatingthesympatheticnervoussystem.
DIAGNOSTICCRITERIA
HTNisdefinedasanelevationinSBPand/orDBP.HTNisnotdiagnosedonaninitialreading;rather,it
isconfirmedafteratleast2readingsatleast1weekapart.BPmeasurementsshouldbeobtainedafterthe
patienthashadtimetorelaxforatleast5minutes.Patientsshouldbeseatedinachair,backsupported
(ratherthanonanexaminationtable),withfeetonthefloor,legsuncrossed,andarmsupportedatheart
level.Patientsshouldavoidsmokingcigarettes30minutesbeforethereading,shouldnotexerciseheavily
immediately before the reading, should not drink caffeine during the hour preceding the reading, and
shouldavoidadrenergicstimulants,suchasphenylephrine.Foranaccuratereading,theappropriatesize
sphygmomanometercuffshouldbeused.Thecuffshouldencompass80%ofthearm,andthewidthofthe
cuffshouldbeatleast40%ofthelengthoftheupperarm(U.S.PreventiveServicesTaskForce,2007).
Attheinitialevaluation,BPshouldbemeasuredinbotharms.Ifthereadingsaredifferent,thearmwith
thehigherreadingshouldbeusedformeasurementsthereafter.Itispreferabletotaketworeadings,1to2
minutesapart,andusetheaverageofthesemeasurements.Inolderpeople,itisusefultoobtainstanding
BP,after1minuteandagainafter3minutes,tocheckforposturaleffects.
Ambulatory BP monitoring (ABPM) is recommended for patients with suspected variable BP.
Contributingfactorscaninclude“whitecoathypertension,”episodic HTN,HTNresistanttoincreasing
medicationregimens, hypotensive symptomswhile taking antihypertensive medications, and autonomic
dysfunction.PatientswithwhitecoathypertensionhaveapersistentlyelevatedBPinthedoctor’soffice
butapersistentlynormalBPatothertimes.ABPMreadingscorrelatebetterwithtargetorgandamagethan
clinical measurements. ABPMalso identifies patients in whomBP does not drop significantlyduring
sleep. More aggressive treatment may be necessaryfor these patients, who are knowntobe at higher
cardiovascularrisk.AnelevatedsystolicBPisamorepotentcardiovascularriskfactorthananelevated
diastolicBP.
In 2014, the Eighth Report of the Joint National Committee (JNC 8) was published. The updated
guidelinesestablishednewdefinitionsforHTNandremovedtheclassificationsthathadexistedinJNC7
(Table18.1).
TABLE18.1
DefinitionofHypertensionoftheEighthReportoftheJointNationalCommittee
PatientPopulation BP(mmHg)
<60yearsold >140/90
>60yearsold >150/90
>18yearsoldwithCKDordiabetes >140/90
BP,bloodpressure;CKD,chronickidneydisease.
Two studies withintheprimaryliterature, systolic hypertensionintheelderlyprogram (SHEP) and
systolichypertensioninEurope,usedplacebo-controlledapproachestoevaluatepeopleovertheageof
60withsystolicHTN,andtheHypertensionintheVeryElderlyTrial(HYVET)evaluatedpatientsover
theageof80.TheJNC8panelcouldnotrecommendalowerthresholdvalueforthoseover60sinceno
evidenceexistedthatasystolicBPlessthan140mmHgwasbetterthanasystolicBPlessthan150mm
Hgforprotectingpatientsfromharm.
In 2017, the American College of Cardiology (ACC) and American Heart Association (AHA)
publishedaGuidelineforthePrevention,Detection,Evaluation,andManagementofBloodPressurein
Adults.ThisguidelinerecommendscategorizingBPintofourstagestoreflectdatasuggestingagradientin
CVDriskastheBPincreases. Notably,theBPcategoriesthathadbeenspecifiedbyJNC7(andsince
removedbyJNC8)differsignificantlyfromthoseinthemostrecentACC/AHAguidelines(Table18.2).
ThediagnosisofHTNshouldbeconfirmedatanadditionalpatientvisit,usually1to4weeksafterthe
firstmeasurement.Onbothoccasions,theSBPandDBPshouldbe higherthanrecommendationslisted
previouslyperage.TheU.S.PreventiveServicesTaskForcerecommendsBPmonitoringinadultpatients
over theageof18. IftheBPisveryhigh (SBP>180 mmHg), initiationof theappropriate triageand
treatmentshouldoccur.Ifavailable resourcesare notadequatetopermitaconvenientsecondvisit,the
initialdiagnosiscanbemadeandtreatmentcanbestarted.
TABLE18.2
2017 American College of Cardiology/American Heart Association Classification of Blood
Pressure
SystolicBP DiastolicBP
Classification (mmHg) (mmHg)
Normal <120 <80
Elevated 120-129 <80
Stage1HTN 130-139 80-89
Stage2HTN >140 >90
BP,bloodpressure;HTN,hypertension.
PhysicalExamination
Athoroughexaminationshouldbeperformed,includingapersonalhistory,first-degreefamilyhistoryof
CVD, dietary habits,anda history of prescriptionandover-the-counter medications, smoking/tobacco
product use, caffeine intake,alcohol consumption, andherbal products. For patients with documented
HTN,evaluatelifestyleandothercardiovascularriskfactorsorconcomitantdisorderstodeterminethe
extentoftargetorgandamageandtoassessthepatient’soverallcardiovascularriskstatus.Mostprevalent
targetdamageconcernisconcentratedonthecardiovascular,cerebral,andrenaltissues.
Physical examination includes two or more measured, seated BP readings with verification in the
contralateral arm; weight and height; body mass index (BMI); waist circumference; muscle strength;
funduscopyexam;auscultationforcarotid,abdominal,andfemoralbruits;palpationofthethyroidgland;
thoroughexaminationoftheheartandlungs;examinationoftheabdomenforenlargedkidneys,enlarged
liver,masses,andabnormalaorticpulsation;palpationofthelowerextremitiesforedemaandpulses;and
neurologicassessmentforsignofpreviousstroke.
DiagnosticTests
The following laboratory tests should be routinely performed: electrocardiogram, hemoglobin,
hematocrit,complete urinalysis, andcompletechemistry panel (whichincludes serum potassium,SCr,
bloodglucose,andliverfunctiontests),calcium andmagnesium, glycosylatedhemoglobin(hemoglobin
A1c), and fasting lipid panel (9- to 12-hour fast), which includes total cholesterol, low-density
lipoproteincholesterol,high-densitylipoproteincholesterol,andtriglycerides.Furthertestingshouldbe
performedbasedonclinicalfindings.
INITIATINGDRUGTHERAPY
GoalsofDrugTherapy
ThegoalofantihypertensivetherapyistomanageHTN,reducecardiovascularcomplications(including
lipid disorders, glucose intolerance or diabetes, obesity, and smoking), and prevent renal disease.
TreatingHTNcandecrease theriskof stroke by40%, myocardial infarction(MI) by 25%, and heart
failureby50%.Itis importanttoinformpatientsthatthetreatmentofHTNis usuallyexpectedtobea
lifelong commitment and that it can be dangerous for them to terminate without first consulting their
provider(Wheltonetal.,2018).
Treatmentguidelinesarecumbersomeduetothedifferentclassificationsofhypertensivepatientswith
or without comorbidities of diabetes and/or CKD, and elderly versus nonelderly patients. BP goals
specifiedinnationalguidelinesaresummarizedinTable18.3.
Inthepast,guidelineshaverecommendedtreatmentvaluesoflessthan130/80mmHgforpatientswith
diabetes,CKD,orcoronaryarterydisease.However,evidencetosupportthislowertargetislackingand
newer guidelines have increased the BP goal. For instance, the ACCORD trial demonstrated that
aggressivereductionoftheBPtarget(<120/80mmHg)inpatientswithtype2diabetesdidnotreduce
combined cardiovascular and renal outcomes compared with usual care (target BP <140/90 mm Hg)
(Cushmanetal.,2010).Amongsecondaryoutcomes,strokeswerereducedbythelowerBPgoals,butat
theexpenseoftwiceasmanyserioussideeffects.Severalmeta-analyseshavedemonstratedthatlowering
SBPtobelow130mmHgdoesnotreducemortalityratesormostcardiovascularoutcomes(Manciaet
al.,2013).
TABLE18.3
BloodPressureGoals
PatientPopulation BPGoal(mm
Hg)
2014EighthJointNationalCommittee
>60yearsold <150/90
<60yearsold <140/90
>18yearsoldwithdiabetesorCKD <140/90
2020AmericanDiabetesAssociation
Diabetesand10-yearASCVDrisk<15% <140/90
DiabetesandexistingASCVDor10-yearASCVDrisk>15% <130/80
Diabetesandpregnancy <135/85
2017AmericanCollegeofCardiology/AmericanHeartAssociation
Stage1HTNandexistingASCVDor10-yearASCVDrisk>10% <130/80
Stage2HTN <130/80
>65yearsold <130/NA
Comorbidities(diabetes,CKD,stableischemicheartdisease,heartfailure,PAD,secondary
strokeprevention)
<130/80
2012KidneyDiseaseImprovingGlobalOutcomes
Urinealbuminexcretion<30mg/24hours <140/90
Urinealbuminexcretion>30mg/24hours <130/80
ASCVD,atheroscleroticcardiovasculardisease;BP,bloodpressure;CKD,chronickidneydisease;HTN,
hypertension;PAD.
InadultpatientswithHTNanddiabetes,treatmentshouldbe initiatedwhenBPis140/90mmHg or
higher,regardlessofage,pertheJNC8guidelines.TheguidelinesoftheAmericanDiabetesAssociation
2020Standards ofMedicalCare inDiabetes recommenddifferentBPtargetsbasedoncardiovascular
risk.Incontrast,theACC/AHA2017 guidelinesrecommenda goaloflessthan130/80 mmHgforall
patientswithdiabetes.
Diuretics
Therearefiveclassesofdiuretics:carbonicanhydraseinhibitors,thiazides,thiazide-likediuretics,loop
diuretics,andpotassium-sparingdiuretics.CarbonicanhydraseinhibitorsarenotusedforHTNbecause
of their weak antihypertensive effects; therefore, they will not be discussed in this chapter. Diuretics
decreaseBPbycausingdiuresis,whichresultsindecreasedplasmavolume,strokevolume,andcardiac
output. During chronic therapy, their major hemodynamic effect is reduction of peripheral vascular
resistance.Asaresultofdrug-induceddiuresis,adverseeffectsofhypokalemiaandhypomagnesemiamay
leadtocardiacarrhythmias.Patientsatgreatestriskarethosereceivingdigitalistherapy,thosewithleft
ventricularhypertrophy(LVH),andthosewithischemicheartdisease(Table18.4).
ThiazideDiuretics
MechanismofAction
Thiazide diuretics workby increasingthe urinaryexcretion of sodium andchloride in equal amounts.
TheyinhibitthereabsorptionofsodiumandchlorideinthethickascendinglimboftheloopofHenleand
the early distal tubules. The anti-hypertensive action requires several days to produce effects. The
durationofactionofthethiazides requiresa single dailydose to control BP.Thiazide diuretics cause
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