Management of hypertension by Mary Nyambura

MANAGEMENT OF HYPERTENSION
Contents
MANAGEMENT OF HYPERTENSION......................................................................................................1
WHAT IS HYERTENSION?.................................................................................................................3
WHY BOTHER MANAGING HYPERTENSION? .....................................................................................3
WHAT IS THE CLASSIFICATION SYSTEMFOR HYERTENSION?..............................................................4
SUBTYPES AND VARIANTS OF HYPERTENSION...................................................................................6
White coat hypertension (white coat effect).....................................................................................6
Isolated systolic hypertension (ISH)..................................................................................................6
INITIAL EVALUATION OF HYPERTENSIVE PATIENTS............................................................................7
CARDIOVASCULAR DISEASE RISK STRATIFICATION...........................................................................14
APPROACH TO DIAGNOSING SECONDARY HYPERTENSION ..............................................................18
WHAT ARE THE COMPLICATIONS OF HYPERTENSION? ......................................................................8
CARDIOVASCULAR COMPLICATIONS.............................................................................................8
CEREBRAL COMPLICATIONS.........................................................................................................8
RENAL COMPLICATIONS/HYPERTENSIVE NEPHROPATHY................................................................8
WHAT ARE THE RISK FACTORS FOR HYPERTENSION?.........................................................................9
WHAT ARE THE COMMON SYMPTOMS OF HYPERTENSION?..............................................................7
WHAT ARE THE BLOOD PRESSURE CUT OFF VALUES USED IN SCREENING FOR HTN?.........................18
PHYSIOLOGY OF BLOOD PRESSURE....................................................................................................21
PRESSURES IN THE VARIOUS PORTIONS OF THE CIRCULATION.........................................................21
BLOOD PRESSURE REGULATION.....................................................................................................21
SHORT TERMCONTROL OF BP....................................................................................................22
ACTIONS OF SYMPATHETIC SYSTEM ...........................................................................................24
HEART..........................................................................................................................................24
Positive chronotropic effect (↑heart rate)...............................................................................24
Positive Inotropic effect (↑contraction)..................................................................................24
Positive dromotropic (conduction) effects are seen due to stimulation of β1receptors. .............24
PARASYMPATHETIC NERVOUS SYSTEM: MUSCARINIC ACTIONS.......................................................24
2. LONG TERM REGULATION OF BLOOD PRESSURE......................................................................25
RENIN- ANGIOTENSIN-ALDOSTERONE SYSTEM ...............................................................................25
ANTIDIURETIC HORMONE/VASOPRESSIN .......................................................................................26

OTHER HUMORALMECHANISMS INVOLVED IN THE CONTROL OF BLOOD PRESSURE.........................26
MANAGEMENT OF HYPERTENSION....................................................................................................28
PREVENTIVE MEASURES ............................................................................................................28
DEFINITIVE MEASURES ..............................................................................................................29
ANTIHYPERTENSIVE DRUG CLASSES ...............................................................................................31

WHAT IS HYPERTENSION?
Hypertension,whichisanon-communicable disease, isdefined aspersistently elevatedoffice
systolicand/ordiastolicbloodpressure of 140/90 mmHg (JNC8 andESC/ESH) or 130/80mmHg
(ACC/AHA 2017) in subjectsaged18 yearsand above.
Hypertensionisdefinedasthe level of BPatwhichthe benefitsof treatment(either withlifestyle
interventionsordrugs) unequivocallyoutweighthe risksof treatment,asdocumentedbyclinical
trials.
The definitionof hypertensioninthe pediatricpopulationisdifferent. Giventhe lackof outcome
data, the currentdefinitionof HTN inchildrenandadolescentsisbasedonthe normative
distributionof BPinhealthychildren.Because itisamajordeterminantof BPingrowingchildren,
heighthasbeenincorporatedintothe normativedatasince the publicationof the 1996 Working
Group Report.BPlevelsshouldbe interpretedonthe basisof sex,age,andheighttoavoid
misclassificationof childrenwhoare eitherextremelytall orextremelyshort. (See table below)
 Bloodpressure isthe force exertedbycirculatingbloodagainst anyunitareaof the
wallsof the body’sbloodvessels.
 Bloodpressure almostalwaysismeasuredinmillimetersof mercury(mmHg)
because the mercurymanometerhasbeenusedasthe standardreference for
measuringpressure since itsinventionin1846 by Poiseuille.
WHY BOTHER MANAGING HYPERTENSION?
Hypertensionisaseriousmedical conditionthatsignificantlyincreasesthe riskof cardiac, cerebral,
renal and otherdiseases. Hypertensionisamajor cause of premature deathworldwide. In2015 an
estimated1.13 billionpeople worldwide had hypertensionwithmost(about2/3) livinginlow and
middle income countries. Fewerthan1in 5 people withhypertensionhave the problemunder
control.

WHAT IS THE CLASSIFICATION SYSTEM FOR HYPERTENSION?
Hypertension canbe classifiedbasedontwomainparameters;
1) Etiology( etiologicclassificationof hypertension)
2) Bloodpressure cutoff values( formsthe basisof multipleguidelines)
ETIOLOGIC CLASSIFICATION
1) PRIMARY/ESSENTIAL HYERTENSION
No identifiablecause.
Multifactorial etiologyincludinggeneticandenvironmental factors.
Accountsfor approximately 85-95% of cases of hypertensioninadults
Accountsfor 15-20% of cases of hypertensioninchildren<12years.
Age at onsetisbetween25-55 years.
2) SECONDARY HYPERTENSION
Secondaryhypertensionisdue toa specificunderlyingcondition.
Accountsfor 5-15% of casesof hypertensioninadults.
Accountsfor 70-85 % of casesof hypertensioninchildren<12years.
Age at onsetis<25 yearsor >55 years.
ENDOCRINE HYPERTENSION
 Adrenocortical hyperfunction;
Primary hyperaldosteronism(conn syndrome) :mostcommon cause
of secondary hypertension in adults.
Congenitaladrenalhyperplasia
Hypercortisolism(Cushing syndrome)
Licorice ingestion
 Hyperthyroidism
 Pheochromocytoma
 Primaryhyperparathyroidism
 Acromegaly
RENAL HYPERTENSION
 Renal vascularhypertension
Renal arterystenosis
Renal vasculitis
 Polycystickidneydisease
 Chronickidneydisease
 Renal failure
 Glomerulonephritis
 Reninproducing tumors

VASCULAR DISEASES
 Coarctationof the aorta
 Polyarteritisnodosa
 Increasedintravascularvolume
 Rigidityof the aorta
NEUROLOGIC
 Obstructive sleepapnea
 Psychogenic
 Raisedintracranial pressure
MEDICATION
 Sympathomimeticdrugs
 Corticosteroids
 NSAIDS
 Oral contraceptives
RECREATIONAL DRUG USE
 Amphetamines
 Phencyclidine
 Cocaine
RECENT can help you remember the causes of secondary hypertension:
R = Renal
E = Endocrine
C = Coarctation of aorta
E = Estrogen
N = Neurologic
T = Treatment

SUBTYPES AND VARIANTS OF HYPERTENSION
White coat hypertension(white coat effect)
 Definition:arterial hypertensiondetectedonlyinclinical settingsorduring bloodpressure
measurementataphysician'spractice
 Etiology:anxietyexperiencedbythe patient
 Clinical features:consistentlynormal bloodpressure measurementsandnormalizationof
elevatedbloodpressureoutsideof aclinical setting
 Diagnostics:24-hourbloodpressure monitoring
Isolatedsystolichypertension(ISH)
 Definition:increasein systolicbloodpressure(≥140 mm Hg) with diastolicBPwithinnormal
limits(≤90 mm Hg)
 Etiology
o ISH inelderly:decreasedarterial elasticityandincreasedstiffness→ decreased
arterial compliance
o ISH secondarytoincreased cardiacoutput
 Anemia
 Hyperthyroidism
 Chronicaortic regurgitation
 AV fistula
 Clinical features:
o Oftenasymptomatic

o Signsof increased pulse pressure:e.g.,headpounding,rhythmicnodding,or
bobbingof the headinsynchronywithheartbeats
o Symptomsof hypertension(seebelow)
 Prognosis:highriskof cardiovascularevents(MI,stroke,renal dysfunction)
WHAT ARE THE COMMON SYMPTOMS OF HYPERTENSION?
Hypertensionisoftencalledasilentkillersince most people withthe conditionare unaware of its
presence because itmayhave nosignsand symptoms.Whensymptomsoccur,theycaninclude;
 Headachesespeciallyearlymorningheadaches
 Dizziness
 Blurredvision
 Nosebleeds/epistaxis
 Visionchanges
 Tinnitus
 Palpitations
 Chestdiscomfort
Severe hypertensioncancause;
 Nausea
 Vomiting
 Fatigue
 Confusion
 Anxiety
 Chestpain
 Muscle tremors
Secondaryhypertensionusuallymanifestswithsymptomsandsignsof the underlyingdisease e.g.
abdominal bruitinrenal-vasculardisease,edemainCKDordaytime sleepinessinobstructive sleep
apnea.
Hypertensioncanpresentacutelyinconditionsreferredtoashypertensive crises:
 Hypertensiveurgency
 Hypertensiveemergency

WHAT ARE THE COMPLICATIONS OF HYPERTENSION?
CARDIOVASCULAR COMPLICATIONS
 Atherosclerotic coronaryarterydisease
 Aorticdissection
 Aorticaneurysm
 Angina
 MI
 Hypertrophiccardiomyopathy
 Heart failure
 Arrhythmias- e.g.atrial fibrillation
 Peripheral vasculardisease
 Carotidarterystenosis
 Atherosclerosis
CEREBRAL COMPLICATIONS
 CVA
 TIA
 Multi infarctdementia
 Hypertensiveencephalopathy
OCCULAR COMPLICATIONS
 Hypertensiveretinopathy
Arterioscleroticandhypertensionrelatedchangesof the retinal vessels.
Fundoscopicexaminationreveals:
 Cotton-wool spots
 Retinal hemorrhages (i.e., flame-shapedhemorrhages)
 Micro aneurysms
 Macular star (resultsfromexudationintothe macula)
 Arteriovenousnicking
 Marked swellingandprominence of the opticdisk withindistinct
bordersdue to papilledemaandopticatrophy (end-stage disease)
Presence of papilledemainahypertensive patientmayindicatea
hypertensive crisisandwarrantsurgentloweringof the blood
pressure
RENAL COMPLICATIONS/HYPERTENSIVE NEPHROPATHY
 AKI
 ESKD

WHAT ARE THE RISK FACTORS FOR HYPERTENSION?
A riskfactor isany attribute,characteristicorexposure of an individual thatincreasesthe likelihood
of developingadisease orinjury.
Riskfactors forhypertensioncanbe broadlydividedintotwo:modifiableandnon-modifiable risk
factors.
NON-
MODIFIABLE
RISK
FACTORS
MODIFIABLE RISK
FACTORS
AGE Bloodpressure increaseswith
age inbothsexes
OBESITY Directlinear
correlationbetween
BMI andBP
Central obesityα risk
for HTN
GENDER Malesdisplaya higheraverage
bloodpressure.
SALT INTAKE Average intake should
be < 5g/day.
Average intake of 7-
8g/d increasesBP
proportionately.
Highersaltintake also
acceleratesendorgan
damage
GENETICS Hypertensionispolygenicin
inheritance.Childrenof
normotensiveparentshave a
3% possibilityof developing
HTN while the possibilityis45%
inchildrenof both hypertensive
parents
POTASSIUMINTAKE K+
antagonizesthe
biological effectsof
Na+
Potassium
supplementslowerBP
ETHNICITY Black Americans>white
Americans
SATURATED ANDTRANS
FATS
The higherthe intake
the greaterthe risk
for HTN
DIETARY FIBRE Most of the fiber
reducesplasmatotal
and LDL-cholesterol
STRESS Increaseslevelsof
catecholaminesby
sympatheticover
activity.
Chronicstresscan
leadto unhealthy
behaviorsuchas
overeating,smoking

and alcoholism.
TOBACCOUSE OR
EXPOSURE
Nicotine stimulates
adrenergicdrive
raisingBP
ALCOHOL IncreasessystolicBP
more than diastolic
BP
PHYSICALINACTIVITY
CO-EXISTINGDISEASES
E.G. DM,RENAL DISEASE
Sedentarylifestyle
increaseschancesof
weightgain.

MEASUREMENT OF BLOOD RESSURE- 10 STEPS
1. CHOOSE THE RIGHT EQUIPMENT
 A qualitystethoscope
 An appropriatelysizedbloodpressurecuff
 A bloodpressure measurementinstrumentsuchasan aneroidormercurycolumn
sphygmomanometeroranautomateddevice withamanual inflate mode.
 Hand cleansinggel
2. PREPARETHE PATIENT
It isimportantwhenmeasuringbloodpressure tobuildarapportwithyyourpatientto
preventthe white coateffectwhichmaygive you inaccuratelyhighreadings. Therefore,
ensure thatyouintroduce yourself tothe patient,explainthe procedure answeringany
questionstheymayhave andaskfor theirconsent. Youshouldalsoexplaintothemthat
theymay feel some discomfortwhile youinflate the cuff butthatthiswill be shortlived.
Make sure that the patientisrelaxedbyallowing5minutestorelax before the firstreading.
The patientshouldsituprightwiththeirupperarmpositionedsoitislevel withtheirheart
and feetflatonthe floor.
Remove excess clothingthatmightinterfere withthe BPcuff orconstrictbloodflow inthe
arm.
Be sure youand the patientrefrainfromtalkingduringthe reading.
3. HANDSANITIZATION
4. ENSURE YOU HAVESELECTED THE RIGHT CUFF FOR THE PATIENT
Most measurementerrorsoccur by nottakingthe time to choose the propercuff size.Wrap
the cuff around the patient’sarmand use the index line todetermineif the patient’sarm
circumference fallswithinthe range area.Otherwise,choose the appropriate smalleror
largercuff.
The ideal cuff size shouldhave abladderlengththatis80% of the arm circumference,a
widththatis at least40% of the arm circumference anda lengthtowidthratioof 2:1.
Use a standardbladdercuff (12–13 cm wide and35 cm long) formost patients,but have
largerand smallercuffsavailable forlarger(armcircumference>32 cm) andthinnerarms,
respectively.
ARMCIRCUMFERENCE RECOMMENDED CUFF SIZE ( WIDTH X
LENGTH IN CM)
cm in
22-26 8.7-10.2 12X22 (small adult)
27-34 10.6-13.4 16x30 (adult)
35-44 13.8-17.3 16x36 (large adult
45-52 17.7-20.5 16x 42 ( extra-large adult)
5. PLACE THE BP CUFF ON THE PATIENT’SARM
Palpate/locate the brachial arteryandpositionthe BPcuff so that the arterymarker points
to the brachial artery.Wrap the BP cuff snugly aroundthe arm.
6. DETERMINE A ROUGH VALUE FOR THE SBP
Thiscan be done bypalpatingthe brachial or radial pulse andinflatingthe cuff until the
pulse canno longerbe felt.The readingatthispointshouldbe notedandthe cuff deflated.
7. POSITION THE STETHOSCOPE

On the same arm that you placedthe BPcuff,palpate the brachial pulse atthe antecubital
fossaand place the diaphragmof the stethoscope overthe brachial artery.Re- inflate the
cuff to 20-30 mmHg higherthanthe estimatedvalue takenbefore.Thendeflate the cuff at
2-3 mmHgper seconduntil youhearthe firstkorotkoff sound- thisisthe systolicblood
pressure.Continuetodeflate the cuff until the sounds disappear, the fifthkorotkoff sound-
thisisthe diastolicbloodpressure.
8. DOUBLE CHECKINGFOR ACCURACY
If the bloodpressure isgreaterthan140/90, you shouldwaitfor about1-2 minutesand
recheck.
Three BP measurementsshouldbe recorded,1–2 minapart, andadditional measurements
onlyif the firsttwo readingsdifferby>10 mmHg.BP is recordedasthe average of the last
twoBP readings.
The AHA recommendstakingareadingwithbotharms to detectpossible between-arm
differences andaveragingthe tworeadings. Use the armwiththe highervalue as the
reference.
9. EXCLUDING ORTHOSTATICHYPOTENSION
Measure BP 1 minand 3 minafter standingfroma seatedpositioninall patientsatthe first
measurementtoexcludeorthostatichypotension.LyingandstandingBPmeasurements
shouldalsobe consideredinsubsequentvisitsinolderpeople,people withdiabetes,and
people withotherconditionsinwhichorthostatichypotensionmayfrequentlyoccur.
10. Informthe patientof theirreadingandthankthem. If afterrecheckingthe bloodpressure
remainselevated, advicethe patienttheywill needthisrepeatedinthe future.
N/B:Additional measurementsmayhave tobe performedinpatientswithunstableBP
valuesdue toarrhythmias,suchas inpatentswithAF,inwhommanual auscultatory
methodsshouldbe usedasmost automateddeviceshave notbeenvalidatedforBP
measurementinpatientswithAF.

INITIAL EVALUATION OF HYPERTENSIVE PATIENTS
Hypertensionislargelyasymptomatic.The mainpurpose of evaluationis toestablishthe diagnosis
and grade of hypertension andforassessmentof complications,concomitant CV riskfactors,factors
potentiallycontributingtothe developmentof HTN andsecondarycausesof hypertension.
What to assessand documentfor
DEMOGRAPHIC HISTORY  Age
 Gender
 Ethnicity
FAMILY HISTORY  Family history of hypertension
 Premature coronary heart disease
or ischemic stroke in a first –
degree relative (father or brother
<55 years, mother or sister <65
years)
 Type 2 diabetes
 Genetic lipid disorder
 History of renal disease
SOCIAL HISTORY  Smoking status (if stopped smoking
for <12 months, assess as a smoker)
 Alcohol consumption
 Dietary history and salt intake
 Sleep history including snoring
DRUG/MEDIACATION HISTORY  Anti-hypertensive drugtreatment
(bothcurrentand past)
 Other prescription drugs
 hormone replacementtherapy
 recreational drug history
PAST MEDICAL HISTORY  Time of the first diagnosis of
hypertension, including records of
any previous medical screening,
hospitalization,
 Past history of CVD (MI, PCI, CABG,
angina, ischemic stroke, TIA,
peripheral vascular disease [PVD])
 Lipid disorder
 Renal impairment (eGFR<60 if
under age 75)
 Diabetes
 Atrial fibrillation
 If patient is female, history of
hypertension in pregnancy
 If patient is male, history of erectile

dysfunction
MEASURE  Average of two sitting BP
measurements – one sitting
measurement if not above 160/95;
two sitting measurements if the
first is above 160/95
 BMI- thishelpstosettargets forweight
loss
 Waist circumference- thishelps
determine whetherapatienthasthe
metabolicsyndrome orisat riskfor
type 2 diabetes.Riskishighwhenthe
measurementis>102 cm in menor >88
cm in women.
 Non-fasting lipid profile
 Fasting Blood Glucose
PHYSICAL EXAM  Signs of heart failure- LVH can be
suspectedbychestpalpation,and
heartfailure canbe indicatedby
distendedjugularveins,rales onchest
examination,anenlarged liver,and
peripheral edema.
 Neurological exam
 Eyes:If possible,the opticfundi should
be checkedforhypertensiveordiabetic
changesand the areasaround the eyes
for findingssuchasxanthomas.
 Pulse:Itisimportantto check
peripheral pulserates;if theyare
diminishedorabsent,thiscanindicate
peripheral arterydisease.
Comparisonof radial withfemoral
pulse:todetectradio-femoral
delayinaorticcoarctation
 Skininspection:cafe-au-laitpatchesof
neurofibromatosis
(phaeochromocytoma)
CARDIOVASCULAR DISEASE RISK STRATIFICATION
The rationale fortreatmentof hypertensionistopreventcomplications,mainlycardiovascular.
Patientsshould thereforeundergocardiovascularriskstratificationbasedonlevel of bloodpressure,
concomitantriskfactors,targetorgan damage and clinical complications
Riskassessmentprovidesevidence-basedapproachtohelpingthe clinicianandthe patienttomake
appropriate decisionsoneffectivepreventionandmanagementof CVD.
Various CVDriskassessment toolsare availableincluding the WHO/ISHassessmenttools,
specificallythe AFROEcharts for the Kenyancontext.

Recommendationsforpreventionandcare of CVDbasedon individualrisklevel are thenmade,
focusingontobacco and alcohol control,dietarymodification,physical activityandpharmacological
management.
MAJOR RISKFACTORS TOD COMPLICATIONS
 Levelsof systolicand
diastolicBP
 Smoking
 Dyslipidemia:
 total
cholesterol >
5.1 mmol/l,
OR
 LDL > 3
mmol/l,OR
 HDL men< 1
and women<
1.2 mmol/l
 Diabetesmellitus
 Men > 55 years
 Women> 65 years
 Familyhistoryof early
onsetof CVD:
Men aged< 55 years
Womenaged< 65
years
 Waistcircumference:
abdominal obesity:
Men >102 cm
Women> 8 8 cm
 LVH:
basedon
ECG
 Micro
albumin
uria:
albumin
creatine
ratio3–
30
mg/mm
ol
preferabl
y spot
morning
urine
and
eGFR >
60
ml/min
 Coronaryheart disease
 Heart failure
 Chronickidneydisease:
 macroalbuminuria>30
mg/mmol
 OR eGFR < 60 ml/min
 Stroke or TIA
 Peripheral arterial
 Disease
 Advancedretinopathy:
 hemorrhagesOR
 exudates
 papilledema

These charts indicate 10-yearriskof a fatal or non-fatal majorcardiovascularevent (Myocardial
infarctionorstroke),accordingtoage, sex,bloodpressure,smokingstatus,total bloodcholesterol
and presence orabsence of diabetesmellitusfor14 WHO epidemiological sub-regions.
There are twosetsof charts.One set can be usedinsettingswhere bloodcholesterol can be
measured.
The other setisfor settingsinwhichbloodcholesterolcannotbe measured.
Both setsare available accordingtothe 14 WHO epidemiological sub‑regions.
Each chart can only be usedincountriesof the specific WHOepidemiological sub-region.
 Evaluationof end-organ damage and underlying causes
 Complete bloodcount- anemiamayindicate CKD
 Renal functiontests( serumcreatinine,eGFR,urinalysis)- evidence of kidney
disease
 SerumNa+
, K+
, and Ca2+
and otherelectrolytes- diagnosisof renal disease
pluselectrolyte imbalancemaysuggestrenal orhormonal anomaly
 Urinalysis –evidence of kidneydisease ordiabetes
 TSH
 Electrocardiogram(ECG) - Identifycardiacanomaliessuchasenlargement,
infarction,ventriculardysfunctionetc
 Lipidprofile- Dyslipidemiaisacardiovasculardisease riskfactor

APPROACH TO DIAGNOSING SECONDARY HYPERTENSION
 General indicatorsof secondary hypertension
o Young age (< 30 years) at onsetof hypertension
Onsetof diastolichypertensionatan olderage (> 55 years)
o Abruptonsetof hypertension
o End-organdamage that isdisproportionatetothe degree of hypertension
o Recurrenthypertensivecrises
o Resistanthypertension:hypertensionthatisresistanttotreatmentwithatleast
three antihypertensives of differentclassesincludinga diuretic
DIAGNOSTIC FINDINGS UNDERLYING CONDITION
Hypokalemia
 Connsyndrome
 Renal arterystenosis
Metabolicalkalosisand ↑ aldosterone-to-
renin ratio
 Connsyndrome
Difference in blood
pressure
In both arms
 Takayasuarteritis
 Aorticdissection
 Aorticarch syndrome
 Subclavian steal syndrome
Of upper and
lower limbs
 Coarctationof the aorta distal tothe left
subclavianartery
Daytime sleepiness (Epworth scale, Berlin
questionnaire)
Nondipping in 24-hour blood pressure
monitoring
 Obstructive sleepapnea
Increased 24-hour urinary metanephrines  Pheochromocytoma
↑ Serum calcium, ↑ PTH level, ↓ serum
phosphates
 Hyperparathyroidism
↑ Serum cortisol
 Excessof glucocorticoids (e.g., Cushing
syndrome)
↓TSH, ↑ free T4  Hyperthyroidism
WHAT ARE THE BLOOD PRESSURE CUT OFF VALUES USED IN SCREENING FOR HTN?
Guidelineson screeningforhypertensionhave beenissuedbydifferentorganizationsincluding;

 Jointnational committeeonprevention,detection,evaluationandtreatmentof highblood
pressure(JNC)-2003 JNC7 & JNC8
 Americancollege of obstetriciansandgynecologists (ACOG)
 Europeansocietyof hypertension(ESH)/Europeansocietyof cardiology(ESC)- 2013 & 2018
guidelines
 Americancollege of cardiology(ACC)/Americanheartassociation(AHA)
 UnitedStatesPreventive ServicesTaskForce(USPSTF)- 2015 guidelines
JNC 7 GUIDELINES
CATEGORY SYSTOLIC DIASTOLIC
NORMAL <120 <80
PREHYPERTENSION 120-139 80-89
STAGE 1 HYPERTENSION 140-159 90-99
STAGE 2 HYPERTENSION ≥160 ≥100
ESH/ESC GUIDELINES
CATEGORY SYSTOLIC DIASTOLIC
OPTIMAL <120 AND <80
NORMAL 120-129 AND/OR 80-84
HIGH NORMAL 130-139 AND/OR 85-89
GRADE 1 HYPERTENSION 140-159 AND/OR 90-99
GRADE 2 HYPERTENSION 160-179 AND/OR 100-109
GRADE 3 HYPERTENSION ≥ 180 AND/OR ≥100
ISOLATEDSYSTOLIC
HYPERTENSION
≥140 AND <90
The newACC/AHA 2017 guidelines(the firstcomprehensive setsince 2003) lowerthe definitionof
highbloodpressure toaccountfor the complicationsthatcan occur at lowernumbersandto allow
for earlierintervention.The newdefinitionwill resultinmore people beingclassifiedas
hypertensive.Thiswill resultinachange inprevalence valuesof hypertensionamongbothmenand
women. Doesthismeanthatmore people will require antihypertensivemedications?
These newguidelineseliminate the category of prehypertension,categorizingpatientsashaving
eitherelevated,stage 1or stage 2 hypertension.
ACC/AHA 2017 GUIDELINES
BP CATEGORY SYSTOLIC BP IN mmHg DIASTOLIC BP IN mmHg
NORMAL < 120 <80
ELEVATED 120-129 <80
STAGE 1 130-139 80-89
STAGE 2 >/= 140 >/= 90
HYPERTENSIVECRISIS >180 >120

Readon the 2016 WHO andUS CDC Global HeartsInitiative.
2017 AAP UPDATED DEFINITIONS OF PEDIATRIC BP CATEGORIES
FOR CHILDREN AGED 1–≤13 Y FOR CHILDREN AGED ≥13 Y
Normal BP: <90th percentile Normal BP: <120/<80 mm Hg
ElevatedBP:≥90th percentileto<95th percentile or120/80
mm Hg to <95th percentile(whicheverislower)
ElevatedBP:120/<80 to
129/<80 mm Hg
Stage 1 HTN: ≥95th percentile to<95th percentile+12 mmHg, or
130/80 to 139/89 mm Hg (whicheveris lower)
Stage 1 HTN: 130/80 to
139/89 mm Hg
Stage 2 HTN: ≥95th percentile +12 mm Hg,or ≥140/90 mm Hg
(whicheverislower) Stage 2 HTN: ≥140/90 mm Hg
2016 EUROPEAN SOCIETY OF HYPERTENSION GUIDELINES FOR THE
MANAGEMENT OF HIGH BLOOD PRESSURE IN CHILDRENAND
ADOLESCENTS

PHYSIOLOGY OF BLOOD PRESSURE
PRESSURES IN THE VARIOUS PORTIONS OF THE CIRCULATION
 Because the heart pumps blood continually into the aorta, the mean pressure in the
aorta is high, averaging about 100mmHg. Also, because heart pumping is pulsatile,
the arterial pressure alternates between a systolic pressure level of 120mmHg and
a diastolic pressure level of 80mmHg.
 As the blood flows through the systemic circulation, its mean pressure falls
progressively to about 0mmHg by the time it reaches the termination of the superior
and inferior venae cavae where they empty into the right atrium of the heart.
 The pressure in the systemic capillaries varies from as high as 35mmHg near the
arteriolar ends to as low as 10mmHg near the venous ends, but their average
“functional” pressure in most vascular beds is about 17mmHg, a pressure low
enough that little of the plasma leaks through the minute pores of the capillary walls,
even though nutrients can diffuse easily through these same pores to the outlying
tissue cells.
 In the pulmonary arteries, the pressure is pulsatile, just as in the aorta, but the
pressure is far less: pulmonary artery systolic pressure averages about 25mmHg
and diastolic pressure averages about 8mmHg, with a mean pulmonary arterial
pressure of only 16mmHg.
 The mean pulmonary capillary pressure averages only 7mmHg. Yet, the total blood
flow through the lungs each minute is the same as through the systemic circulation.
 The low pressures of the pulmonary systemare in accord with the needs of the lungs
because all that is required is to expose the blood in the pulmonary capillaries to
oxygen and other gases in the pulmonary alveoli.
BLOOD PRESSURE REGULATION
Blood pressure is a functionof CARDIAC OUTPUT and TOTAL ERIPHERAL RESISTANCE bothof which
are influencedbymultiplegeneticandenvironmental factors.Cardiacoutputisitself afunctionof
STROKE VOLUME and HEART RATE. Heart rate isregulatedbythe α and β adrenergicsystemswhile
stroke volume isdependentona numberof cardiac and non-cardiacfactorswhichinclude;
1) Myocardial contractility
2) Sodiumandwaterhomeostasis
3) Mineralocorticoids
4) Atrial natriureticpeptides
Peripheral resistance isregulatedpredominantlyatthe level of the arteriolesbyneural andhumoral
inputs.

CONSTRICTORS VS DILATORS
(α- adrenergic ) (β- adrenergic)
NEURAL FACTORS
BLOOD PRESSURE=CARDIAC OUTUTX TOTAL PERIPHERAL RESISTANCE LOCAL
FACTORS
STROKE VOLUME X HEART RATE HUMORAL FACTORS
Mineralocorticoids β adrenergicsystem
Myocardial contractility
Sodiumandwaterhomeostasis
CONSTRICTORS VS DILATORS
AngiotensinII prostaglandins
Catecholamines kinins
Thromboxane NO
Leukotrienes
Endothelin
SHORT TERM CONTROL OF BP
1.NEURAL CONTROL
a) CARDIOVASCULAR CONTROL CENTRES

The cardiovascularcontrol centersof the CNS are locatedinthe medullaoblongata(i.e.brainstem)
inclose proximitytothe centersregulatingrespiration.The CCChave two majorsubdivisionsthat
innervate the heartandperipheral vasculature withsignificantanatomical andfunctional overlap;
 The cardiac control center
Thiscan furtherbe subdividedintotwo;
 The cardioinhibitorycenter- containsparasympatheticvagal efferentstoreduce
heartrate and to a lesserextentatrial contractility.
 The cardiostimulatorycenter- increasesmyocardial contractilityandheartrate via
activationof the sympatheticnervoussystem.
 The vasomotor center
Thiscan alsobe subdividedintothree;
 The vasoconstrictorarea(C-1)- containsa highconcentrationof neuronssecreting
noradrenaline.Thisareahasbeen proposedasone of the sitesof clonidine,which
bindsto presynapticα2receptorsinhibitingrelease of NA thusreducingTPR.
Neuronsinthisareasendvasoconstrictorfiberstothe peripheryviathe sympathetic
nervoussystem.
 The vasodilatorregion(A-1)- inhibitsthe activityof C-1
 A sensoryarea(A-2)- receivesinputfromcranial nervesIXandXand the efferent
neuronsprojecttothe vasoconstrictorandvasodilatorareasandhence modulate
output.
The CCC receivesmodulatoryneural inputfromvarious otherregionswithinthe brainincluding;
 The motor cortex
 Frontal cortex
 Limbicsystem
b) VASOMOTOR TONE
Thisis the sumof the muscularforcesintrinsictothe bloodvessel opposinganincrease in
vessel diameter.Thisismediatedbyvascularsmoothmuscle cells(VSMC) inthe medialayer
of vessel walls.Vasomotortone hasvariousdeterminants,includingthe autonomicnervous
system,humoral agentsandautacoids.
Basal vasomotortone is mediatedbylow level,continuousimpulsesfromthe SNSin
additionto partial arteriolarandvenularconstrictionviaVSMCcontraction.Circulating
adrenaline fromthe adrenal medullamaycomplementthis.
Basal tone is maintainedataround50% of maximumconstriction.
c) BARORECEPTOR REFLEXES
In response to ACUTECHANGES IN BLOOD PRESSURE, the bodyrespondsthroughthe baroreceptors
locatedwithinbloodvessels.Baroreceptorsare aform of mechanoreceptorthatbecome activated
by the stretchingof the vessel.Thissensoryinformationisconveyedtothe central nervoussystem’s
cardiovascularcontrol centers(CCC) andusedtoinfluence peripheral vascularresistance andcardiac
output.
There are twoformsof baroreceptors;

 HIGH PRESSURE BARORECEPTORS
A fewbaroreceptorsare locatedinthe wall of almosteverylarge arteryof the thoracic and
neckregions,butbaroreceptorsare extremelyabundantin ;
 The wall of eachinternal carotidarteryslightlyabove the carotidbifurcation,anarea
knownas the carotidsinus- signalsfromthe “carotidbaroreceptors”are transmitted
throughsmall Hering’snervestothe glossopharyngealnervesinthe highneck,and
thento the nucleustractussolitariusinthe medullaryareaof the brainstem.
 The wallsof the aorticarch- Signalsfromthe “aortic baroreceptors”inthe arch of
the aorta are transmittedthroughthe vagusnervestothe same nucleustractus
solitariusof the medulla.
Afterthe baroreceptorsignalshave enteredthe nucleustractussolitariusof the medulla,secondary
signalsinhibitthe vasoconstrictorcenterof the medullaand excite the vagal parasympathetic
center. Dependingonthe bloodpressure statusthe neteffectsare:
ACTIONS OF SYMPATHETIC SYSTEM
HEART
 Positivechronotropiceffect (↑heartrate)
 PositiveInotropiceffect (↑contraction)
 Positive dromotropic(conduction) effectsare seendue tostimulationof β1receptors.
BLOOD VESSELS
 Stimulationofα1 receptors causes vasoconstriction
 β2 stimulationleadstodilationofbloodvessels.
PARASYMPATHETIC NERVOUS SYSTEM: MUSCARINIC ACTIONS
HEART
Parasympatheticsystemhasinhibitoryeffectonthe heart(M2) and is responsible forthe;
 negative chronotropic(decreasedheart rate)
 Negativedromotropic(decreased conduction) effects.
BLOOD VESSELS
No directcholinergicsupplyispresentinbloodvesselsbutcholinergicreceptors(M3) are presenton
endotheliumof bloodvessels.Stimulationof these receptorscausesrelease of NOfrom
endotheliumresultingin vasodilation.

Additional mechanismof vasodilationisinhibitoryactionof AChonnor-adrenaline release from
tonicallyactive vasoconstrictornerve endings.
However,if endotheliumisdamaged,AChcanstimulate M3receptorsinthe vascularsmoothmuscle
leadingtovasoconstriction.
 Low pressure baroreceptors
These baroreceptorsare presentwithinthe low pressure venoussystem.Theyexistwithin;
 Large veins
 Pulmonaryvessels
 Wallsof the rightatriumand ventricle
CHEMORECEPTOR REFLEXES
The aortic and carotidbodiesalsocontainchemoreceptorswhichrespondtoreductionsinthe
arterial partial pressure of O2 andincreasesinthe arterial partial pressure of carbondioxide.
2. LONG TERM REGULATIONOF BLOOD PRESSURE
RENIN- ANGIOTENSIN-ALDOSTERONE SYSTEM
Reninisa peptide hormone releasedbythe granularcellsof the juxtaglomerularapparatusinthe
kidneyinresponse to;
 Sympatheticstimulation
 Reducedsodiumchloridedeliverytothe distal convolutedtubule
 Decreasedrenal perfusion
Reninfacilitatesthe conversionof angiotensinogentoangiotensinIwhichisthenconvertedto
angiotensinIIusingangiotensinconvertingenzyme.
AngiotensinIIisa potentvasoconstrictor.Aslittleasone millionthof agram can increase the arterial
pressure of a humanbeing50 mmHg or more.The importance of angiotensinIIisthatitnormally
acts on manyof the arteriolesof the bodyat the same time to increase the total peripheral
resistance.
The other functionof angiotensinIIistoincrease sodiumreabsorptioninthe proximalconvoluted
tubule.
AngiotensinIIalsopromotesrelease of aldosterone.
ACE alsobreaksdownbradykininwhichisapotentvasodilator.Therefore,the breakdownof
bradykininpotentiatesthe overallconstrictingeffect.
Aldosteronepromotessaltandwaterretentionbyactingat the distal convolutedtubule toincrease
expressionof epithelial sodium channels(ENaCs).

Aldosteronealsoincreasesthe activityof the basolateral sodiumpotassiumATP-ase thusincreasing
the electrochemical gradientformovementof sodiumions.
ANTIDIURETIC HORMONE/VASOPRESSIN
It isevenmore powerful thanangiotensinIIas a vasoconstrictor,thusmakingitone of the body’s
mostpotentvascularconstrictorsubstances.
It is synthesizedinthe magnocellularneurosecretorycellsinthe paraventricularnucleusand
supraopticnucleusof the hypothalamusbutisthentransported downwardbynerve axonstothe
posteriorpituitarygland,where itisfinallysecretedintothe blood.
Triggersfor ADH release include;
 Highserumosmolaritywhichactson hypothalamicosmoreceptors
 Low bloodvolume whichcausesadecrease instretchof low pressure baroreceptors
 Low BP whichcausesa decrease inthe stretchof highpressure baroreceptors.
Once produced,ADHacts to increase the permeabilityof the collectingducttowaterby inserting
aquaporinchannels(AQP2) intothe apical membrane.
It isclear that vasopressincouldhave enormouseffectsoncirculatoryfunction.Yet,because only
minute amountsof vasopressinare secretedinmostphysiological conditions,mostphysiologists
have thoughtthat vasopressinplayslittlerole invascular control.
OTHER HUMORALMECHANISMS INVOLVED IN THE CONTROL OF BLOOD PRESSURE
VASODILATOR AGENTS
 Bradykinin.-Several substancescalledkininscause powerful vasodilationwhenformedin
the bloodand tissue fluidsof some organs.The kininsare small polypeptidesthatare split
away byproteolyticenzymesfromα2-globulinsinthe plasmaortissue fluids.A proteolytic
enzyme of particularimportance forthispurpose iskallikrein,whichispresentinthe blood
and tissue fluidsinaninactive form.Thisinactive kallikreinisactivatedbymacerationof the
blood,tissue inflammation,orothersimilarchemical orphysical effectsonthe bloodor
tissues.Askallikreinbecomesactivated,itactsimmediatelyonα2-globulintorelease akinin
calledkallidinthat isthenconvertedbytissue enzymesintobradykinin.Once formed,
bradykininpersistsforonlyafew minutesbecause itisinactivatedbythe enzyme
carboxypeptidase orbyconvertingenzyme,the same enzymethatalsoplaysanessential
role inactivatingangiotensin.The activatedkallikreinenzyme isdestroyedbyakallikrein
inhibitoralsopresentinthe body fluids.Bradykinin causesbothpowerful arteriolardilation
and increasedcapillarypermeability.Forinstance, injection of 1 microgramof bradykinin
intothe brachial artery of a personincreasesbloodflow throughthe armas muchas six fold,
and evensmalleramountsinjectedlocallyintotissuescancause markedlocal edema
resultingfromincrease incapillarypore size. Kininsappeartoplayspecial rolesinregulating
bloodflowandcapillaryleakage of fluidsininflamedtissues.Italsoisbelievedthat
bradykininplaysanormal role tohelpregulate bloodflow inthe skin,aswell asinthe
salivaryandgastrointestinal glands.

 Histamine.- Histamine isreleasedinessentiallyeverytissueof the bodyif the tissue
becomesdamagedorinflamedoristhe subjectof an allergicreaction.Mostof the histamine
isderivedfrommastcellsinthe damagedtissuesandfrombasophilsinthe blood.Histamine
has a powerful vasodilatoreffectonthe arteriolesand,like bradykinin,hasthe abilityto
increase greatlycapillaryporosity,allowingleakage of bothfluidandplasmaproteinintothe
tissues.Inmanypathological con-ditions,the intensearteriolardilationandincreasedcapil-
laryporosityproducedbyhistamine cause tremendousquantitiesof fluidtoleakoutof the
circulationintothe tissues,inducingedema.
 Nitricoxide- NO isdeemedtobe one of the mostimportantmediatorsof vascularhealth.It
can be synthesizedbyone of three isoformsof nitricoxide synthase(NOS):constitutive
endothelial(eNOS),neuronal(nNOS) andinducible endothelial (iNOS).Beyondvasomotor
function,NOalsohasinhibitoryeffectsonplateletaggregation,local inflammatory
responsesandmitogenesis.
 Prostaglandins-theyactas local vasodilatorstoincrease GFRand reduce sodium
reabsorption.Theyalsoactto preventexcessivevasoconstrictiontriggeredbythe
sympatheticsystemandthe RAAS.

MANAGEMENTOF HYPERTENSION
PREVENTIVE MEASURES
1. NUTRITION AND HEALTHY DIET
Healthydietarypracticesstartearlyinlife.A healthypregnancyislikelytoyieldahealthybaby.
Breastfeedingfostershealthygrowthandimprovescognitive development,andmayhave long-term
healthbenefitslikereducingthe riskof becomingoverweightorobese anddevelopingCVDslaterin
life.
 Energyintake (calories) shouldbe inbalance withenergyexpenditure.
 Total fatshouldnotexceed30% of total energyintake toavoidunhealthyweight
gain.
 Shiftinfat consumptionawayfromsaturatedfatstounsaturatedfats,and towards
the eliminationof industrial trans-fats.
 Limitingintake of refinedsugarstolessthan10% of total energyintake ispart of a
healthydiet. A furtherreductiontolessthan5% of total energyintake issuggested
for additional healthbenefits.
 RECOMMENDATIONSFOR SALT REDUCTION ;
 Adults:consume lessthan5 g (justundera teaspoon) of saltperday.
 Children:consume lessthan3g of saltper day
 All saltthat isconsumedshouldbe iodizedor“fortified”withiodine,which
isessential forhealthybraindevelopmentinthe fetusandyoungchildand
optimizingpeople’smental functioningeneral.
 Avoidprocessedfoodssuchasbread, crisps
 Avoidaddingsaltat the table while eating.
2. PHYSICAL ACTIVITY
Patientsshouldbe encouragedtoengage ina varietyof physical activitiesandtoprogressively
increase theiractivityastolerated. Individualswithahistoryof CVDshould consulttheirhealthcare
providerbefore they undertake vigorousphysical activity.
Recommendations:
• Childrenandadolescentsaged5-17yearsshoulddoat least60 minutesof moderate tovigorous-
intensityphysical activitydaily.
•Adultsshoulddoat least150 minutesof moderate-intensityphysical activitythroughoutthe week.
•Those withpoor mobilityshouldperformphysical activitytoenhance balance andpreventfalls,3
or more days perweek.
•Muscle-strengtheningactivitiesshouldbe done involvingmajormuscle groups,2or more days a
week.
3. RECOMMENDATIONS FOR WEIGHT MANAGEMENT
 Limitenergyintake fromtotal fatsandsugars;
 Increase consumptionof fruitandvegetables,aswell aslegumes, wholegrainsandnuts;
(referto Nutritionandhealthy dietsection)

 Engage in regularphysical activity.(Refertophysical activitysection)
4. TOBACCO DEPENDENCE TREATMENT,CESSATIION AND PREVENTION
Healthcare professionalsshouldprovide regularandtailoredcounselinginterventionsforthose who
meetthe criteriafortobacco dependence.Tobaccodependencetreatmentandcessationprograms
shouldcombine behavioral support(suchaspsychological interventions,telephone supportandself-
help) withpharmacotherapytreatmentwhere necessary.Before decidingon whichinterventionto
use,itis essential todocumenttobaccouse statusandconductscreening.Healthcare providersof
tobacco dependence treatmentandcessationshouldreceive suitabletraining.
There are three maincategoriesof interventions:
a. Brief advice(5As) bya healthcare professional
The 5As approach isan evidencebasedframeworkforstructuringtobacco
dependence treatmentandcessationbrief interventioninhealthcare and
communitysettings.The 5Asfortobacco cessationare Ask,Advice,Assist,
AssessandArrange
b. Behavioral support
Behavioral supportaimsatchangingthoughtprocessesandbeliefs.If one changesthe
waytheyfeel abouttobaccouse,a change inbehaviorshouldfollow.The healthcare
providerhelpsthe persontodeal with negative feelingsandassiststhe clientsinsetting
realisticgoalstoavoidfailure.
Behavioral strategies thatcansupporta clienttocope withthe triggersand high-risk
situationsfortobaccouse include:
 Face to face support
 Individual behavioral counseling
 Group behaviortherapy
 Telephone counselingorquitlines
 Self-helpmaterials
c. Pharmacotherapy
The pharmacological interventionsinclude:
1. Nicotine replacementtherapies
 Nicotine gums
 Nicotine patches
 Nicotine lozenges/sublingual tablets
 Nicotine inhalers
 Nicotine nasal spray
2. Non-Nicotinereplacementtherapies
 Bupropion
 Varenicline
DEFINITIVE MEASURES
NONPHARMACOLOGICINTERVENTIONS
 Avoidance of alcohol- Hypertensivemenwhodrinkalcohol shouldbe advisedtolimittheir
consumptionto14 unitsperweekandwomento8 unitsperweek (1unitis equal to125 mL
of wine or250 mL of beer).Alcohol-free daysduringthe weekandavoidance of binge
drinking35are alsoadvised.

 Avoidance of all formsof tobacco
 Dailyadequate physical exercise: Hypertensive patientsshouldbe advisedtoparticipate in
at least30 minof moderate-intensitydynamicaerobicexercise (walking,jogging,cyclingor
swimming) on5–7 daysper week.Performanceof resistance exerciseson 2 - 3 days per
weekcanalso be advised.
 Consumptionof ahealthydiet:Hypertensive patientsshouldbe advisedtoeatvegetables,
low-fatdairyproducts,dietaryandsolublefibre,whole grainsandproteinfromplant
sources,reducedinsaturatedfatand cholesterol,Freshfruits.Avoidaddedsaltandhigh salt
food.
Regularconsumptionof sugar-sweetenedsoftdrinkshasbeen associatedwithoverweight,
metabolicsyndrome,type 2diabetes, andhigherCV risk.The consumptionof thesedrinks
shouldbe discouraged.Thus,adoptingahealthyandbalanced dietmayassistinBPreduction
and alsoreduce CV risk.
 Weightreduction:foroverweightandobese hypertensive patients. Weightlossshould
employamultidisciplinary approachthatincludesdietaryadvice,regularexercise,and
motivational counselling.Furthermore,short-termresultsare oftennotmaintainedoverthe
long-term.Weightlosscanalsobe promotedbyanti-obesitydrugsand,toa greaterdegree,
bariatricsurgery,whichappearstodecrease CV riskinseverelyobese patients.
PHARMACOLOGICINTERVENTIONS
The diagnosisof hypertensionanddecisiontobeginantihypertensivemedicationrequireselevated
SBP and/orDBP measurementsconfirmedonatleast3 separate occasionsover a2-monthperiodas
well asthe cardiovascularrisklevel of the patient.
The overall healthandfrailtyof anelderlypersonshouldbe assessedbefore makingadecision to
start antihypertensive therapy.If there isdoubtorconcern about the healthstatusof the patient,
theyshouldbe referred toa specialistforfurthermanagement.
RATIONALE FOR PHARMACOLOGICTREATMENT OF HYPERTENSION.
Patientswithprimaryhypertensionare generallytreatedwithdrugsthat;
1) REDUCE CARDIACOUTPUT BY;
 Reducingthe stroke volume
 Reducingthe heartrate
 Reducingbloodvolume
2) REDUCE SYSTEMIC VASCULARRESISTANCE
Patientswithsecondaryhypertensionare besttreatedbycontrollingorremovingthe underlying
disease/pathologyalthoughtheymaystill require antihypertensive drugs.

ANTIHYPERTENSIVE DRUG CLASSES
 DIURETICS
 RAASINHIBITORS
 NITRODILATORS/NITRATES
 POTASSIUMCHANNELOPENERS
 CALCIUMCHANNELBLOCKERS
 ALPHA ADRENOCEPTORANTAGONISTS
 BETA BLOCKERS
 CENTRALLY ACTINGSYMPATHOLYTICS
1. DIURETICS
NORMAL REABSORTION SITES FOR SODIUM
As bloodflowsthroughthe kidneys,itpassesintoglomerularcapillarieslocatedwithinthe cortex.
These glomerularcapillaries are highlypermeable towaterandelectrolytes.
The proximal convoluted tubule,which lieswithinthe cortex,is the site of Na+
,H2O and HCO3
–
transportfrom the filtrate acrossthe tubule andintothe interstitiumof the cortex.
 65-70% of the filteredsodiumisreabsorbedinthe PCT.
 Sodiumisabsorbedisosmotically.
The thick ascendinglimb,whichisimpermeable towater,hasa co transportsystemthat reabsorbs
sodium,potassiumandchloride ionsata ratio of 1:1:2.
 25% of the filteredsodiumisreabsorbedinthe TAL.
The early DCT (alsoimpermeabletowater) isanothersite forsodiumreabsorptionviaaNa+
-Cl-
co-
transporter.
 5% of the filteredsodiumisreabsorbedatthe DCT.
The distal segmentof the DCT and the uppercollectingducthasa transporterthat reabsorbssodium
(1-2% of the filteredload) inexchange forpotassiumandhydrogenwhichare excretedintourine.
 The activityof thistransporteris dependentonthe tubularconcentration of sodium.
 Thistransporterisregulatedbyaldosterone ( amineralocorticoid)
GENERAL MECHANISMSOF ACTION OF DIURETICS
DIURETICS

DIURESIS + NATRIURESIS
DECREASED BLOOD VOLUME AND VENOUS PRESSURE
DECREASED PRELOAD
DECREASED STROKE VOLUME
DECREASED CARDIACOUTPUT
DECREASED ARTERIALPRESSURE
N/B:longterm use of diureticsresultsinafall insystemicvascularresistance byunknown
mechanisms.
DIURETIC
DRUG CLASS
EXAMPLES MECHANISM OF
ACTION
ADVERSE EFFECTS CONTRAINDICATIONS
AND DRUG
INTERACTIONS
LOOP
DIURETICS
(notindicated
for mildto
moderate
hypertension)
 Bumetanide
 Furosemide
 Torsemide
 Ethacrynicacid
 Indacrinone (
can be usedin
gout patients.it
inhibitsuric
acid
reabsorption)
Inhibitthe Na+
-K+
-2Cl
-
co-transporterin
the TAL.
These drugsalso
induce renal
synthesisof
prostaglandins
whichcontributesto
increasedrenal
bloodflow and
redistributionof
renal cortical blood
flow.
 HYPOKALE
MIA
 METABOLIC
ALKALOSIS
 DEHYDRATI
ON(HYPOV
OLEMIA)
LEADING
TO
HYPOTENSI
ON
 HYPERURIC
EMIA
(EXCEPT
INDACRINO
NE)
 HYPOMAG
NESEMIA
 OTOTOXICI
TY( DOSE
RELATED
HEARING
LOSSS.
 HYPOTENSION
 RENAL
IMPAIREMENT
 SLE
 ANURIA
 HYPOKALEMIA
POTENTIATES
DIGITALISAND
LITHIUM
TOXICITY
 AMINOGLYCO
SIDES
ENHANCE
OTOTOXICITY
AND
NEPHROTOXIC
ITY
THIAZIDE and
THIAZIDE-LIKE
DIURETICS
 Chlorthiazide
 Chlorthalidone
- longt1/2
Inhibitthe Na+
-Cl-
co-transporter in
the earlyDCT.
 HYPOKALE
MIA
 METABOLI
 GOUT
 HYPOKALEMI
A

(1st
LINE
DRUGS FOR
HYPERTENSIO
N)
 Hydrochlorothi
azide
 Hydroflumethi
azide
 Indapamide(
Thiazide like in
action, more
potent and
longeracting
than HCTZ, can
be usedin
diabetessince
others are
contraindicate
d)
 Methyclothiazi
de
 Metolazone(
thiazide like in
action, not
structure)
 polythiazide
C
ALKALOSIS
 HYPERURIC
EMIA( at
low doses)
 HYPERGLYC
EMIA( in
diabetics)
 HYPONATR
EMIA
 DEHYDRATI
ON
(HYPOVOLE
MIA)
LEADING
TO
HYPOTENSI
ON
 AZOTEMIA(
in renal
disease
patients)
 ↑LDL
 HYPERCHO
LESTEROLE
MIA AND
HYPERTRIG
LYCERIDEM
IA
 HYPERCALC
EMIA
 IMOTENCE
POTENTIATES
DIGITALIS
AND LITHIUM
TOXICITY
 β-BLOCKERS
POTENTIATE
HYPERGLYCE
MIA AND
HYPERLIPIDE
MIA
 CORTICOSTER
OIDS
ENHANCE
HYPOKALEMI
A
 NSAIDS
CAUSE
↓DIURETIC
EFFICACY
K+
SPARING
DIURETICS
Amiloride(distaltubule
Na channel inhibitor)
Eplerenone(
aldosterone receptor
antagonist)
Spironolactone(
aldosterone receptor
antagonist)
Triamterene(distal
tubule Nachannel
inhibitor)
Some drugsin this
classantagonize the
actionsof
aldosterone
(aldosterone
receptor
antagonists) atthe
distal segmentof the
DCT.
Othersdirectly
inhibitNa+
channels
associatedwiththe
aldosterone
sensitiveNa+
pump.
 HYPERKALE
MIA
 METABOLIC
ACIDOSIS
 ALDOSTER
ONE
ANTAGONI
STS CAUSE
GYNECOM
ASTIA
 GASTRIC
PROBLEMS
e.g.PUD
 ALDOSTERONE
ANTAGONISTS
MAY ↓ RENAL
EXCRETION OF
DIGOXIN
 ACEIs
POTENTIATE
HYPERKALEMI
A
CARBONIC
ANAHYDRASE
INHIBITORS
 Acetazolamide
(notusedin
HTN or CCF)
 Dichlorphenam
ide (notusedin
Inhibittransportof
HCO3
–
at the PCT.
Rarelyusedin
cardiovascular
disease.Mainuse is

HTN or CCF
 Methazolamid
e( not usedin
HTN or CCF)
intreatmentof
glaucoma.
GOOD TO KNOW
2. VASODILATORS
2.1 RAAS INHIBITORS
NORMAL RAAS PATHWAY
SYMPATHETIC STIMULATION (β1 RECEPTORS)
HYPOTENSION
DECREASED Na+
DELIVERY
JUXTAGLOMERULAR CELLS OF KIDNEYSECRETE RENIN
RENIN CATALYZESCONVERSION OFANGIOTENSINOGEN TOANGIOTENSIN 1
ANGIOTENSIN IISCONVERTED TO ANGIOTENSIN IIBY ACE(alsoknownas Kininase II)
 An insignificantamountof angiotensinIIisalsoproducedbychymase
enzyme(nonACEpathway)
 ACE isalsoinvolvedinthe breakdownof bradykinin,apotentvasodilator
ANGIOTENSIN IIACTSON AT1 (MAIN ACTION) ANDAT2 (LESSIMPORTANT) RECEPTORS
EFFECTS INCLUDING;
 systemicvasoconstriction(directeffect)
Glaucoma ischaracterized by progressive
damage to optic nerve associated with raised
intraocular pressure (> 21 mm Hg). Rise in
intraocular tensionis eitherdue to excessive
production or due to lessdrainage ofaqueous
humor. So, the drugs usedfor glaucoma act by
eitherdecreasingthe secretion (β-blockers, α2
agonistsand Carbonicanhydraseinhibitors) or
by increasingthe outflow(miotics,dipivefrine
and prostaglandins)ofaqueoushumor.

 systemicvasoconstriction( indirectlyby↑ releaseof adrenaline fromthe
adrenal medullaand↑ central sympatheticoutflow)
 ↑aldosteronerelease- renal sodiumandwaterretention
 ↑ADHsecretionfromthe pituitary- waterretention
 cardiac and vascularhypertrophy( aldosteroneeffects)
RAASDRUG
CLASS
EXAMPLES MECHANISM
OF ACTION
ADVERSEEFFECTS CONTRAINDICATIONS
RENIN
INHIBITORS
Aliskiren
Remikiren
Enalkiren
Inhibitthe
enzyme renin
ACEIs
(1ST
LINE
THERAPY,
CLEARED BY
ENAL
EXCRETION)
 Captopril-
1ST
ACEIto
be
marketed,
lesspotent,
fastonset,
short
durationof
action,less
absorption
inpresence
of food
 Enalapril
 Lisinopril
 Ramipril
 Perindopril
 Fosinopril
 Moexipril
 Trandolapril
 Quinapril
Competitive
antagonistsof
ACE thus
inhibit
angiotensinII
formation
leadingto;
Arterial and
venous
vasodilation(
whichresults
in↓arterial
and venous
pressure as
well as
↓afterload
and reload),
Decreased
bloodvolume,
Depressed
sympathetic
activityand
Inhibitionof
cardiac and
vascular
hypertrophy.
 DRY COUGH
 ANGIOEDEMA
 1ST
DOSE
HYPOTENSION
 HYPERKALEMIA
 RASHES
 DYSGUESIA(alte
redtaste
sensation)-
captopril
 ACUTE KIDNEY
INJURY (if used
inbilateral renal
arterystenosis)
 BILATERAL
RENAL
ARTERY
STENOSIS
 PREGNANCY-
ACEIsare
teratogenic.
Theycause
renal
dysplasia,
renal failure,
oligohydramni
os,
hypoplastic
calvaria,IUGR,
pulmonary
hypoplasia
 BREASTFEEDI
NG
ARBS  Losartan
 Candesartan
 Eprosartan
 Irbesartan
 Olmesartan
 Telmisartan
 Valsartan
BlockAT1
receptors
Losartan is
alsoa
competitive
antagonistof
TXA2 and
attenuates
platelet
aggregation
 Orthostatic
hypotension
 Hyperkalemia
 Rash
 Dizziness/heada
che
 Acute kidney
injuryif usedin
bilateral renal
arterystenosis
 Pregnancy
 Breastfeeding
 Aortic
stenosis
 Bilateral renal
artery
stenosis
ALDOSTERO
NE
ANTAGONIS
TS
Spironolactone
Eplerenone
Block
aldosterone
receptors
 Gynecomastia
 Hyperkalemia
 Metabolic
acidosis

ACEIS ARE PREFERRED AS A FIRST-LINE DRUG IN PATIENTS WITH DIABETES MELLITUS, RENAL
DISEASE (NEPHROPROTECTIVE),ISCHEMIC HEART DISEASE, AND HEART FAILURE
ACEI AND ARBS SHOULD NOT BE USED IN COMBINATION.
GOOD TO KNOW
2.2 NITRODILATORS/NITRATES
Nitricoxide isproducedfromthe aminoacidL- arginine bythe enzymaticactionof nitric
oxide synthase (NOS).There are two endothelial formsof NOS;constitutiveNOS(cNOS;
typeIII) andinducible NOS(iNOS;type II).InadditiontoendothelialNOSthere isaneural
NOS(nNOS;type I) that servesatransmitterinthe brainand efferentnervesof the
peripheral nervoussystem.
Vasculareffectsof NOinclude;
 Directvasodilation(flow dependentandreceptormediated)
 Indirectvasodilationbyinhibitingvasoconstrictorinfluences
 Antithrombotic- inhibitsplateletadhesion
 Anti- inflammatory- inhibitsleukocyteadhesion,scavengessuperoxide anion
 Anti-proliferative effect- inhibitssmoothmuscle hyperplasia
Nitrodilatorsmimicthe actionsof endogenousNObyreleasingNOorformingNO
withintissues.
There are twobasictypesof nitrodilators;
 Those that release NOspontaneously
Sodiumnitroprusside
 Organicnitratesthat require anenzymaticprocesstoformNO
Isosorbide dinitrate
Isosorbide mononitrate
ARBsact a distal site so they
will inhibit the activity of
RAAS even when
angiotensin II is generated
by the non ACE pathway.

Nitroglycerin
Erythrityl tetranitrate
Pentaerythritol tetranitrate
MECHANISMOF ACTION OFNO:
1. Nitricoxide activatessmoothmusclesolubleguanylyl cyclase toformcGMp
IncreasedintracellularcGMPinhibitscalciumentryintothe cell thereby
decreasingintracellularcalciumconcentrationcausingsmoothmuscle
relaxation.
2. NO activatesK+
channelswhichleadsto hyperpolarizationandrelaxation
3. NO actingthrough cGMP can stimulate acGMP dependentproteinkinasethat
activatesmyosinlightchainphosphatase,the enzyme thatdephosphorylatesmyosin
lightchainsleadingtorelaxation.
ORGANICNITRATES SODIUMNITROPRUSSIDE
TOLERANCE occurs withfrequent
dosingwhichdecreasestheirefficacy.
Thisis circumventedbyusingthe
smallesteffective dose of the
compoundcoupledwithinfrequentor
irregulardosing. The mechanismof
tolerance mayinvolve depletionof
tissue sulfhydryl groupsorscavenging
of NOby superoxide anionandthe
subsequentroductionof peroxynitrite
that may inhibitguanylyl cyclase.
Dilatesarterial resistancevessels>venous
vessels
Prolongedadministrationleadsto
cyanide accumulationespeciallyrenal
patients
HYPOTHYROIDSM due to accumulation
of thiocyanate ( antithyroidcompound)
CONTRAINDICATEDinpregnancy.
VENOUSDILATION>ARTERIAL DILATION
whengivenatnormal therapeutic
doses.
Rapidonsetof action
Usedextensivelytotreatanginaand MI Usedin hypertensive emergenciesand
severe cardiacfailure.
Oral bioavailabilityof manyorganic
nitratesis low because of hepaticfirst
pass metabolism( exceptIsosorbide
mononitrate)
Onlyavailable asanIV preparation.
Metabolitesare biologicallyactive and
have a longerhalf-life thanthe parent
compound.
Short half-life hence continuousIV
infusionrequired.
Unstable andsensitive tolight
Bioavailability
 It is the fraction of administereddrugthat reaches
the systemiccirculationin the unchangedform.
 Whenwe administera drug orally, first it isabsorbed
into the portal circulationand reachesthe liver.Here,

SIDE EFFECTS OF NITRODILATORS
 Headache- secondarytocerebral vasodilation
 Cutaneousflushing
 Reflex tachycardia
 Postural hypotension
2.3 POTASSIUMCHANNEL OPENERS
Usedfor severe refractoryhypertension.
Include;
 Minoxidil
 Diazoxide
 Hydralazine
MECHANISMOF ACTION
Activate ATPsensitive K+
channelsinvascularsmoothmuscle.
Hyperpolarizationof smoothmuscle
Closure of voltage gatedCa2+
channels
↓intracellularCa2+

WithlessCa2+
available tocombine withcalmodulin,there islessactivationof myosin
lightchainkinase &phosphorylationof myosinlightchains
Relaxationandvasodilation
MUST KNOW:
Hydralazine ismetabolizedbyacetylationandthusitseffectisgeneticallydetermined
due to the presence of slowandfastacetylators.
On prolongedadministration,hydralazine canleadtodrug inducedlupuserythematosis.
Minoxidil isaprodrugand isactivatedinthe livertoproduce Minoxidil sulphate ( by
phase II reaction)
SIDE EFFECTS
1. MINOXIDIL
Headaches
Flushing
Reflex tachycardia
Fluidretentionandedema
AnginainpatientswithCAD
T wave changes
Hypertrichosis
Hirsutism(utilized fortreatmentof alopeciain males)
2.4 CALCIUMCHANNEL BLOCKERS
CHEMICAL CLASSES OF CCBs
Differnotonlyintheirbasicchemical structure butalsoin theirrelative selectivity
towardcardiac versusvascularL type Ca2+
channels.
DIHYDROPIRIDINES
( mostsmoothmuscle
selectiveclass/peripherally
actingCCBs- hence used
for HTN)
PHENYLALKYLAMINES
( usedinhypertrophic
obstructive
cardiomyopathy,PSVTand
angina)
BENZOTHIAZEPINES
( usedinhypertrophic
obstructive
cardiomyopathy,PSVTand
angina)
Amlodipine verapamil diltiazem
Felodipine norverapamil
Nicardipine- longestacting,
DOC inhypertensive
emergencies
Nifedipine- hasnatriuretic
properties,↑riskof MI and
mortality
Isradipine
Nimodipine-relatively
cerebro-selective,usedto
reverse the compensatory
vasoconstrictionafterSAH

Nitredipine
Clevidipine –ultrashort
actingDHP
lacidipine
MECHANISMOF ACTION:
Blockthe L type calciumchannelslocatedonthe vascularsmoothmuscle,cardiac
myocytes,andcardiac nodal tissue (SAN,AVN)
Vascularsmoothmuscle relaxation(vasodilation)
Decreasedmyocardial contractility( -ve inotropy)
Decreasedheartrate ( -ve chronotropy)
Decreasedconductionvelocitywithinthe heart(-ve dromotropy)
SIDE EFFECTS
DHPS
 flushing
 headache
 excessivehypotension
 edema
 reflex tachycardia
 rash
NDHPS
 Bradycardia
 AV block
 Depressedcontractility
CONTRAINDICATIONS
CARDIOSELECTIVECCBS:
 pre existingbradycardia
 conductiondefects
 ccf secondaryto systolicdysfunction
 patientsonbetablockers
MUST KNOW:
CCBS undergofirstpassmetabolism.
CCBS are hepaticenzyme inhibitors.
2.5 ALPHA ADRENOCEPTOR ANTAGONISTS (α blockers)
α1 SELECTIVE ADRENOCEPTOR ANTAGONISTS
 prazosin
 doxazosin
 terazosin

 trimazosin
NON- SELECTIVE α1 BLOCKERS
 phentolamine
 phenoxybenzamine
Vascularsmoothmuscle hastwotypesof α adrenoceptors.
α1- predominantα receptoronvascularsmoothmuscle.Gq linked;activatesmoothmuscle
contractionviathe IP3 signal transductionpathway
α2 –Gi linked;↓ cAMP;smoothmuscle contraction.Those locatedpresynapticallyinhibit
release of NE
α1 antagonisteffects- vasodilationof botharteriesandveinsbutarteries>veins.
SIDE EFFECTS
 Orthostatichypotension
 Nasal congestion
 Headache
 Reflex tachycardia
 Dizziness
3. BETA BLOCKERS
NON SELECTIVE BETA BLOCKERS
 Carteolol
 Carvedilol
 Labetalol
 Nadolol
 Pindolol
 Propranolol
 Sotalol
 Timolol
B1 SELECTIVE
 Atenolol
 Esmolol
 Metropolol
 Bisoprolol
 Nebivolol
 Betaxolol
M.O.A: bindto betaadrenoceptorsandtherebyblockthe bindingof NEand E thusinhibiting
sympatheticeffectsthatact throughthese receptors(sympatholytics)
CARDIAC EFFECTS:

↓contractility(-veinotropy)
↓relaxationrate (-velusitropy)
↓heartrate (-ve chronotropy)
↓conductionvelocity(-vedromotropy)
VASCULAR EFFECTS:
vasoconstriction
SIDE EFFECTS:
 Bradycardia
 ↓exercisecapacity
 Heart failure
 Hypotension
 AV block
 Peripheral vasoconstrictioninskeletalmuscle beds- coldextremities/Raynaud’s
phenomenon
 Maskinghypoglycemia
 Bronchoconstriction
 Hallucinations
 Vividdreamsandnightmares
4. DRUGS INHIBITING CENTRAL SYMPATHETIC FLOW( CENTRALLY ACTING SYMPATHOLYTIC
DRUGS)
α2 AGONISTS- include;
 clonidine
 methyldopa
 guanabenz
 guanfacine
SIDE EFFECTS:
 Sedation
 Dry mouthand nasal mucosa
 Bradycardia(due to ↑ vagal stimulationof the SAN)
 Orthostatichypotension
 Impotence
 Nausea,constipation
 Fluidretentionandedema
 Abruptdiscontinuationof clonidine resultsinreboundhypertension(treatedwith
phentolamine)

 Methyldopacauseshemolyticanemia

ANTI-HYPERTENSIVE DRUG DOSES
RESISTANTHYERTENSION
Thisis definedasBP≥ 140/90 mmHg despite treatmentwithatleastthree drugs( includinga
diuretic) inadequate dosesandafterexclusionof false hypertensionsuchasisolatedoffice
hypertensionandfailure touse large cuffsonlarge arms.

CATEGORY POSSIBLECAUSES INTERVENTIONS
NON-ADHERENCETOTHERAPY  Instructionsnot
understood
 Side effects
 Cost of medication
and/orcost of attending
at healthcare center
 Lack of consistentand
continuousprimarycare
 Inconvenientandchaotic
dosingschedules
 Organicbrain syndrome
(e.g.memorydeficit)
 Adherence counseling
 Ensure family/social
supportmechanismfor
the patient
 Tailordosingschedules
to individualpatients
VOLUME OVERLOAD  Excesssaltintake
 Inadequate diuretic
therapy
 Progressive renal
damage
(nephrosclerosis)
Counsel onlow saltdiet,
optimize diuretictherapy,
referas appropriate
ASSOCIATEDCONDITIONS  Smoking
 Increasingobesity
 Sleepapnoea
 Insulin
resistance/hyperinsulina
emia
 Ethanol intake of more
than 30 g (three
standarddrinks) daily
 Anxiety-induced
hyperventilationorpanic
attacks
 Chronicpain
 Intense vasoconstriction
(Raynaud’s
 phenomenon),arteritis
Manage the associated
condition
IDENTIFIABLECAUSESOF
HYERTENSION
 Renovasculardisease
 Primaryaldosteronism
 Coarctation
 Cushing’ssyndrome
 Phaeochromocytoma
Investigate and/orrefer
PSEUDORESISTANCE  Whitecoathypertension’
or office elevations
 Pseudohypertensionin
olderpatients
 Use of regularcuff in
obese patients
 Out of office BP
measurement
 Ensure properBP
measurement
technique
DRUG RELATED CAUSES  Dosestoo low
 Wrong type of diuretic
Review treatmentplan

 Inappropriate
combinations
 Rapidinactivation(e.g.
hydralazine)
DRUG ANDFOOD
INTERACTIONS
 Non-steroidal anti-
inflammatorydrugs
(NSAIDs)
 Sympathomimetics:
nasal decongestants,
appetite
 Steroids(e.g.
prednisolone and
hydrocortisone)
Remove offendingdrugand
referforspecialistcare.
NON PRESCRIPTION DRUG USE
• Recreational drugs(e.g.
cocaine,amphetamines,and
anabolicsteroids)
• Excessive liquorice ingestion
• Herbal remedies(e.g.ephedra
and mahuang)
TREATMENTOF HYPERTENSION IN PREGNANCY
 First-linetreatment:methyldopa;,labetalol,hydralazine (vasodilator),andnifedipine (CCB)
 Second-line treatment:thiazides,clonidine (alpha-2agonist)
 Contraindicated:furosemide,ACE-I,ARB,renininhibitors(aliskiren)
TREATMENTOF HYPERTENSION IN CHILDREN
 Treat the underlyingcause (e.g.,surgical correctionof coarctationof the aorta)
 Lifestyle changesinchildrenwithelevatedBP(
 Pharmacologicmanagementisindicatedforsymptomatichypertension, diabetesmellitus,
CKD,and end-organdamage,aswell asif there isan insufficientresponse ornoresponse to
lifestyle changes.
o Goal: BP < 90th
percentile (BP <50th
percentile inchildrenwithDMor CKD)
o Drugs: ACE inhibitor,ARB,orcalciumchannel blocker
 In childrenwith CKDordiabetesmellitus, ACEinhibitors orARBsare
preferable.
 Hypertensiveemergency:labetalol, nicardipine,orsodiumnitroprusside
o Beta blockers are notrecommendedforinitial treatmentof hypertensioninchildren
due to theirmetabolicside effects(e.g., impairedglucose tolerance) andthe fact
that theyexacerbate asthma!

HYPERTENSIVECRISES
Hypertensivecrisesare acute,severe elevationsinbloodpressure thatmayor maynot be
associatedwithtarget-organdysfunction.Hypertensive emergencies,asubsetof hypertensive
crises,are characterizedbyacute,severe elevations inbloodpressure,oftengreaterthan180/110
mm Hg (typicallywithsystolicbloodpressure [SBP] greaterthan200 mmHg and/ordiastolicblood
pressure [DBP] greaterthan120 mm Hg) associatedwiththe presence orimpendence of target-
organ dysfunction.Hypertensive urgenciesare characterizedbya similaracute elevationinblood
pressure butare not associatedwithtarget-organdysfunction.
Althoughhypertensive emergenciescanleadtosignificantmorbidity andpotentiallyfatal target-
organ damage,only1%–3% of patientswithhypertensionwillhave ahypertensiveemergency
duringtheirlifetime (Deshmukh2011). Withinthe hypertensive crises, hypertensive emergencies
account foronlyaround one-fourthof presentationscomparedwithhypertensiveurgencies,which
account foraround three-fourths(Zampaglione 1996).Despite the low incidence of hypertensive
emergencies,hospitalizationsbecause of hypertensive emergencieshave increasedsince 2000
(Deshmukh
2011), possiblybecause of the heightenedawareness,recognition,andsubsequentdiagnosisof
hypertensive emergency.However, eventhoughmore hospitalizationsare secondaryto
hypertensive
emergencies,mortalityremainslow,withanin-hospitalmortality of around2.5% and1- and10-year
survival greaterthan90% and 70%, respectively(Deshmukh2011; Lane 2009; Webster1993).
Many riskfactors and causesare associatedwiththe development of hypertensive crises.Inasmall
longitudinalanalysisfrom Switzerland,hypertensive crises were more oftenassociatedwith female
sex,highergradesof obesity,presence of hypertensive orcoronaryheartdisease,presence of
mental illness, andhighernumberof antihypertensive medications,with the strongestassociation
relatedtopatientnon-adherence toantihypertensivemedications(Saguner2010).
Causesvarynationally,regionally, andinstitutionally,butcommon causesinclude;
 intoxications(e.g.,cocaine,amphetamines, phencyclidine hydrochloride,stimulantdiet
supplements),
 non-adherencetoantihypertensive regimens,
 withdrawal syndromes(e.g.,clonidine orβ-antagonists),
 drug-drug/drug-foodinteractions(e.g.,monoamine oxidaseinhibitorsand tricyclic
antidepressants,antihistamines,ortyramine),
 spinal corddisorders,
 Pheochromocytoma
 pregnancy,
 collagen vasculardisease (e.g.,systemiclupus erythematous)

TREATMENTGOALS
 Treatmentgoalsforhypertensive crisesdependonclassification (e.g.,emergencyvs.
urgency) andpresentingcondition.
 Many presentingconditionshave unique treatmentgoals, includingtime togoal,additional
treatmentparameters, andtreatmentmodalities,toachieve setgoals.These conditions are
consideredexceptionstothe general treatment principlesof hypertensive crisisandinmost
recentguidelines termed“compellingconditions.
 For the general treatmentof hypertensive crisis,patientsshouldbe classifiedashaving
hypertensive emergencyorhypertensiveurgency.
 Hypertensiveurgencyoftenrequiresinitiating,reinitiating, modifying,ortitratingoral
therapyand usuallydoes notrequire ICUorhospital admission.
 The treatment target for hypertensive urgencyis a gradual blood pressure reductionover
24–48 hours to the goals as laidout in the most recentrenditionof hypertension
managementguidelinesonthe basis of compellingindications.

 The more commonerror withthe treatmentof hypertensive urgencyisoveraggressive
correctionbecause nobenefit,butpotential harm, maybe associatedwithtoorapida
decrease inbloodpressure.
 Avoidingoveraggressivecorrectionisparticularlyimportantinpatientswithchronic
hypertensionbecause theirendorgansadaptto chronicallyelevatedbloodpressures,
settinga newphysiologic“norm”of autoregulation.
 Thisnew “norm” leadstooptimal organperfusionata higherbaselinebloodpressure.If this
autoregulatoryshiftisunrecognizedduringahypertensiveemergency,patientsmaybe at
riskof harm fromovercorrectionorover-normalizationof bloodpressure.
 In the treatmentof hypertensiveemergency,patientswhowouldfall intothe general
treatmentgoalsshouldbe identified,asshouldthose whowouldhave exceptionstothe
general treatmentgoals(compellingconditions).
 For patientswithout exceptions,the goal of therapy isto reduce the mean arterial
pressure (MAP) by 25% over the first hour of therapy
 Greaterreductions(bymore than25%) have beenassociatedwiththe inductionof cerebral
ischemia
 In addition,if neurologicdeteriorationisnotedduringthe initial 25% MAP reduction(or
duringsubsequentlowering),therapyshouldbe discontinued.
 Afterthe firsthour,a more gradual bloodpressure reductionisrecommended.
 For individual populationsthatqualifyforexceptionstothe general treatmentgoals
(compellingconditions),seethe textbelow.
 These populationsincludepatientswithaorticdissection,acute stroke (ischemicand
hemorrhagic),andpregnancy-associatedsevere hypertension(preeclampsia/ eclampsiaand
hypertensive emergencyinthe pregnantpatient)
 Each of these populationshasunique treatmenttargets,considerationsforsubpopulations
withinthem,oradditional considerationsduringtreatment.
TREATMENTOF HYPERTENSIVEEMERGENCY
Giventhe diverse presentationsof hypertensiveemergency,itischallengingtolabel one medication
as the drug of choice.Infact,systematicreview hasfailedtoshow the superiorityof anymedication
or medicationclasstoanotherregardingclinical outcomesof hypertensive emergency.
Choice of medicationoftendependsonarisk-benefitanalysisof eachagentconsideringthe
 affectedtargetorganon presentation,
 pharmacokinetics(PK)andpharmacodynamics(PD) of the medicationsavailable,
 Hemodynamic,adverseeffectandBPV profile of the medication options.
Preferable traitsof medicationsusedtotreathypertensive emergenciesinclude
 intravenousadministration,
 abilitytobe titratedto desiredeffectallowingfora
 “smooth”reductionof bloodpressure,
 short durationof activity,
 Minimal adverse effectprofile.
Extreme cautionshouldbe usedwithacute andprofoundloweringof bloodpressure,giventhat
over-normalizationhasledtothe inductionof ischemic
MEDICATIONSUSED IN HYPERTENSIVEEMERGENCY

 Sodiumnitroprusside isapotent arterial andvenousvasodilatorthathasbeenused
extensivelyinthe treatmentof hypertensive emergencybecause of itsfavorable PK
parameters.
 Sodiumnitroprusside isanitricoxide donor,leadingtosmoothmuscle relaxation.
 Because itworksdirectlyatsmoothmuscle,sodiumnitroprussidereducesbothafterload
and preload,givingitwide applicabilityforvarioushypertensive emergencies.
 Two PD effectsof concernwithsodiumnitroprusside are “coronary steal”andincreasesin
ICP.Coronarysteal isthe conceptof redistributingoxygenatedbloodfromdiseasedcoronary
arteriestowardnon-diseasedcoronaryarteriesbecause non-diseasedcoronaryarteriescan
preferentiallyvasodilate.
 In theory,thiswouldthenshuntoxygenatedbloodaway fromischemicareas.
 Sodiumnitroprusside mayresult inthis preferential vasodilation,leadingtoreduced
coronary perfusion pressure ,andthusshouldbe avoided inpatientspresentingwith
myocardial infarctionastheirtargetorgandamage.
 In additiontothe PD concernswithsodiumnitroprusside,potentialaccumulationof toxic
metabolitesisaconcern.
 Sodiumnitroprusside containscyanide moleculesthatare releasedduringadministration.
 Under normal circumstances,the cyanide thatisreleasedisbound bymethemoglobin-
formingcyanomethemoglobin).
 The remainingcyanide moleculesare convertedtothiocyanate bytranssulfurationinthe
liver,whichisthenexcreted inthe urine bythe kidneys.
 Patientswithchronicliverdisease, alcoholism,andmalnourishmentmayhave adecreased
capacityfor transsulfuration,leadingtoanimpairedabilityto detoxifycyanide.
 Signsof cyanide accumulationinclude
 decreasedmental
 status
 headache,
 vomiting,
 agitation
 lethargy
 coma
 tachyarrhythmias
 tachypnea
 bloodpressure lability
 unexplained lacticacid
 aniongap
 metabolicacidosis,
 shock
 death
 Although cyanide accumulationisarisk withsodiumnitroprusside,undernormal conditions,
patients candetoxify50mg of sodium nitroprusside,whichwill then require dosesgreater
than 10 mcg/kg/minute formore than 16 hours forgreaterthan 10% methemoglobinemia
(i.e.,toxicity)
 Of note,aboxedwarningexistsregarding cyanide exposure,witharecommendationto
avoidmaximum doses(i.e.,10mcg/kg/minute) formore than10 minutes, especiallyin
patientsatriskof accumulation,asnotedearlier.
 Highdosesare rarelyusedinclinical practice;therefore, cyanide toxicityisunlikelyin most
patientsduringthe acute treatmentphase.

 If toxicityis inquestion,carboxyhemoglobin and/ormethemoglobinserumconcentrations
can be sentinadditiontolaboratoryteststo elucidate lacticacidosis,and arterial and
venousbloodgases canbe obtainedtocompare the Po2 gradient(e.g.,narrowingof
venous-arterial Po2thatoccurs withcyanide toxicity).
 Cyanide concentrationsare usuallynotprocessedatmostinstitutionsandserve mainly as
confirmatory.
 If cyanide toxicityissuspected,discontinuationof sodium nitroprusside isrecommended,
togetherwithtreatmentwith eitherintravenoushydroxycobalaminandsodiumthiosulfate
or sodiumnitrite andsodiumthiosulfate.
 Thiocyanate accumulationmaycause toxicitybutis consideredlesstoxicthancyanide.
 In addition,thiocyanatehasalonghalf-life(3–7days),whichrequireshighdoses(usually
greaterthan 3 mcg/kg/minute) andextensivetreatment durations(greaterthan72 hours) to
accumulate.
 Signsof thiocyanate toxicityare relativelynonspecificbutmayinclude
 fatigue
 tinnitus
 nausea
 vomiting
 hyperreflexia
 alteredmental
 status
 miosis
 Giventhe relative nonspecificsignsof thiocyanate toxicity,serum concentrationassayscan
be beneficialif processedina time-sensitivefashion.
 Because thiocyanate iseliminatedby the kidneys,cautioniswarrantedforprolongeduse in
patients withacute renal failure whopresentwithtarget-organdamage inhypertensive
emergency,thoughshort-termuse (less than24 hours) shouldbe safe (Adebayo2015; Ram
2009).
 If thiocyanate accumulationissuspected,managementstrategies includediscontinuingthe
sodiumnitroprusside infusion, usingsupportive care,orusinghemodialysistoenhance
clearance (Nessim2006).
 One lastconsideration isthe relativecostof sodium nitroprusside.Inrecentyears,the cost
pervial of sodium nitroprusside hasconsiderablyincreasedbyaround200% in some
instances.Althoughgenericproductsare becoming more available,costanalyzesare vital in
evaluatingthe use of these products ona largerscale.
 Because of the aforementionedconcernssurrounding the use of sodiumnitroprussideasa
first-lineagent,otheragentshave beeninvestigatedextensively.
 The CCBs are one such classof medications andincludethe dihydropyridine intravenous
agentsnicardipine andclevidipine andthe non-dihydropyridine agentsdiltiazemand
verapamil (Rhoney

 2009).
 The dihydropyridine agentsare peripherallyselective L-typeCCBsthatexerttheir
antihypertensive effectsby inhibitingcalciuminflux throughcalciumchannelsalongthe
vascularsmoothmuscle. Thisinhibitionpreventssmooth muscle contractility,leadingto
vasodilationandreductionin systemicbloodpressure.
 These agentspreferentiallybindto peripheral L-type calciumchannelsin the cerebral,
coronary, peripheral,andrenal vascularsmooth.
 In contrast, the non-dihydropyridineagents diltiazemandverapamilhave preferential
effectsinthe heart inthe order of the conductionsystemsandcontractile myocardial cellsin
addition totheirperipheral effects.
 Because of these negative inotropicandchronotropiceffects,these agentsare usuallyonly
usedforselectpresentationsof hypertensivecrisis.
 Whencomparingthe dihydropyridineCCBswithsodiumnitroprusside,these agentsdonot
affect
 ICPand may be considered preferentialforpatientswith acute stroke asthe target-organ
damage on presentationof hypertensive emergency(Hemphill 2015; Gaab 1985).

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