Hypertension

Pharmacotherapy I
First Semester 2013-2014
References
Ch. 19 (Hypertension) in Pharmacotherapy; a pathophysiologic approach. 8th edition 2011.
Ch. 14 (Essential hypertension) in pplied !herape"tics# !he Clinical $se o% &r"gs' ed. (oda)(im*le' 10th
edition' 201+.
,oint -ational Committee on Pre.ention' &etection' E.al"ation' and !reatment o% High /lood Press"re. !he
se.enth report o% the ,oint -ational Committee on Pre.ention' &etection' E.al"ation' and !reatment o% High
/lood Press"re. (,-C 0) ,1 200+; 289#2230)02.
201+ E4H5E4C 6"idelines %or the management o% arterial hypertension# the !as7 8orce %or the management
o% arterial hypertension o% the E"ropean 4ociety o% Hypertension (E4H) and o% the E"ropean 4ociety o%
Cardiology (E4C). , Hypertens. 201+ ,"l;+1(0)#1281)+20
4H Position rticle. Com*ination therapy in hypertension. ,o"rnal o% the merican 4ociety o% Hypertension
4(1) (2010) 42920.
CC85H 2011 E:pert Consens"s &oc"ment on Hypertension in the Elderly. ,o"rnal o% the merican
College o% Cardiology ;ol. 20' -o. 20' 2011.
Hypertension in the Elderly# Pharmacotherapy 8oc"s. Pharmacist<s =etter. ,"ne 2011.
2
Learning Objectives
1. &escri*e arterial *lood press"re (/P)' the reg"lation o% /P' and the pathophysiology o% hypertension.
2. >denti%y cardio.asc"lar (C;) complications that are associated ?ith hypertension (hypertension)related target)
organ damage) and list ma@or C; ris7 %actors.
+. Classi%y /P as o"tlined *y the 4e.enth Aeport o% the ,oint -ational Committee on Pre.ention' &etection'
E.al"ation' and !reatment o% High /lood Press"re (,-C0).
4. &escri*e the appropriate proced"res and criteria needed to diagnose hypertension.
2. 4tate the o.erall p"rpose o% treating hypertension.
3. >denti%y appropriate /P goals that are determined *ased on patient)speci%ic presentations.
0. >denti%y /P goals recommended *y the ,-C0.
8. Aecommend li%estyle modi%ications %or the management o% hypertension' and descri*e the e%%ecti.eness o% these
modi%ications.
9. B"tline recommended management o% patients ?ith prehypertension and hypertension.
10. Compare and contrast the clinical characteristics (pharmacology5mechanism o% action' *ene%its' ad.erse e%%ects'
interactions' "niC"e dosing considerations' contraindications' and monitoring) o% antihypertensi.e dr"gs.
11. >denti%y %irst)line dr"g therapy options %or hypertension according to the ,-C0.
12. B"tline dr"g therapy recommendations %or patients ?ith hypertension and compelling indications (i.e.' le%t
.entric"lar dys%"nction' post91>' coronary artery disease' dia*etes' chronic 7idney disease' and rec"rrent stro7e
pre.ention)' and descri*e s"pporting e.idence %or these recommendations.
1+. &escri*e special considerations %or antihypertensi.e management in older indi.id"als and those at ris7 %or
orthostatic hypotension.
14. >denti%y the clinical "se and characteristics o% alternati.e antihypertensi.e agents.
12. =ist important components o% patient co"nseling regarding hypertension' li%estyle modi%ication' and dr"g therapy.
13. >denti%y potential ca"ses %or lac7 o% responsi.eness to therapy.
10. &escri*e the rationale' *ene%its' and appropriate "se o% com*ination dr"g therapy %or hypertension.
18. &e.ise appropriate therapy and monitoring plans %or patients ?ith hypertension.
19. Compare and contrast the goals o% treatment and pharmacotherapy %or managing hypertensi.e "rgency and
emergency.
20. >denti%y patients ?ith resistant hypertension and recommend pharmacotherapy %or these patients. 3
Definition
4
Hypertension: Persistent elevation in arterial blood pressure.
Terminology
Arterial BP is the press"re in the arterial ?all
meas"red in millimeters o% merc"ry (mm Hg).
Systolic pressure: the pea7 press"re e:erted in
the arteries ?hen *lood is p"mped into them
d"ring .entric"lar systole.
Diastolic pressure: the lo?est press"re e:erted in
the arteries ?hen *lood is draining o%% into the
.essels do?nstream d"ring .entric"lar diastole.
Pulse pressure: the di%%erence *et?een the
systolic and diastolic press"re (normallyD 40 mm
Hg).
Mean arterial bloo pressure !MAP": the a.erage
press"re responsi*le %or the dri.ing *lood
%or?ard thro"gh the arteries into the tiss"es
thro"gho"t the cardiac cycle
1PD (15+ 4/P) E (25+ &/P)
1PD diastolic press"re E 15+ p"lse press"re
5
#ote:
Historically more emphasis ?as placed on diastolic than on systolic *lood press"re as a predictor o%
cardio.asc"lar mor*id and %atal e.ents.
Ho?e.er' a large n"m*er o% o*ser.ational st"dies has demonstrated that cardio.asc"lar mor*idity
and mortality *ear a contin"o"s relationship ?ith *oth systolic and diastolic *lood press"res.
$piemiology
Forld?ide prevalence o% hypertension is estimated to incl"de 1
*illion indi.id"als. !here are an estimated 0 million deaths per year
that may *e related to the diagnosis o% hypertension.
!he pre.alence o% hypertension di%%ers *ased on age% se&% an
et'nicity
/P .al"es increase (it' age.
1ost patient ha.e pre'ypertension BP .al"es *e%ore they are
diagnosed ?ith hypertension.
1ost hypertension diagnoses occ"r *et?een the t'ir an fift'
ecaes of life)
*p to t'e age of ++ years' more men than ?omen ha.e hypertension.
,rom t'e ages of ++ to -. years' slightly more ?omen ha.e
hypertension than men' ?ith this se: di%%erence *ecoming greater in
the .ery elderly (G02 years).
6
7
$tiology
!he ca"se o% hypertension is "n7no?n in the ma@ority o%
cases (primary hypertension)' *"t %or those ?ith secondary
hypertension' speci%ic ca"ses are indicated.
$ssential or primary 'ypertension# H 90I patients'
hypertension res"lts %rom an "n7no?n pathophysiologic
etiology . !his %orm o% hypertension cannot *e c"red' but it
can be controlle)
Seconary 'ypertension: small percentage o% patients
ha.e a speci%ic ca"se o% their hypertension; either
conc"rrent medical conditions or are endogeno"sly
ind"ced. >% the ca"se can *e identi%ied' hypertension in
these patients 'as t'e potential to be cure.
Pseuo'ypertension
/'ite01oat 2ypertension an Mas3e 2ypertension
Resistant 'ypertension
8
Seconary 1auses of 2ypertension
9
Seconary 1auses of 2ypertension !cont4"
10
Coarctation o% the aorta is a *irth de%ect in ?hich the aorta' the ma@or artery %rom the
heart' is narro?ed. !he narro?ing res"lts in high *lood press"re *e%ore the point o%
coarctation and lo? *lood press"re *eyond the point o% coarctation. 1ost commonly'
coarctation is located so that there is high *lood press"re in the "pper *ody and arms
and lo? *lood press"re in the lo?er *ody and legs. 4ymptoms can incl"de localiJed
hypertension' cold %eet or legs' decreased e:ercise per%ormance' and heart %ail"re
1oarctation of t'e aorta
P'eoc'romocytoma
Pheochromocytoma is a rare t"mor in part o% the adrenal gland. >n most cases' the
t"mors are not cancero"s and do not spread to other parts o% the *ody. /"t' in
a*o"t +0 percent o% cases' the t"mors are cancero"s.
1ost people ?ith pheochromocytoma ha.e hypertension *eca"se the t"mor
ca"ses the adrenal gland to prod"ce too m"ch adrenaline or noradrenaline.
Patients can ha.e attac7s o% high *lood press"re that occ"r in s"dden' short *"rsts'
or the high *lood press"re can *e more contin"o"s and long lasting.
Renovascular isease
Aeno.asc"lar disease is a
progressi.e condition that
ca"ses narro?ing or *loc7age
o% the renal arteries or .eins.
>tKs the general term "sed %or
three disorders#
renal artery occl"sion'
renal .ein throm*osis'
renal atheroem*olism
Pat'op'ysiology
!he pat'op'ysiology of primary 'ypertension is heterogeneo"s'
*"t "ltimately e:erts its e%%ects thro"gh the t?o primary
determinants o% *lood press"re# cariac output an perip'eral
resistance)
1"ltiple %actors that control /P are potential contri*"ting
components in the de.elopment o% essential hypertension.
h"moral (i.e.' the renin9angiotensin9aldosterone system LA4M)
.asodepressor mechanisms (;asc"lar Endothelial 1echanisms)'
a*normal ne"ronal mechanisms'
de%ects in peripheral a"toreg"lation'
and dist"r*ances in sodi"m' calci"m' and natri"retic hormones.
most anti'ypertensives specifically target t'ese mec'anisms an
components of t'e RAAS)
14
15
,actors involve in t'e pat'ogenesis of 'ypertension
17
50 2umoral !role of t'e RAAS"
18
6) #euronal Regulation
Pathologic dist"r*ances in any o% the %o"r ma@or
components o% the ne"roreg"lation system co"ld
concei.a*ly lead to chronically ele.ated /P. !hese
systems are physiologically interrelated#
a"tonomic ner.e %i*ers
adrenergic receptors N1'N2' O1' O2
*aroreceptors' thro"gh the ninth cranial ner.e and
.ag"s ner.es
central ner.o"s system# stim"lation o% certain areas
?ithin the central ner.o"s system (n"cle"s tract"s
solitari"s' .agal n"clei' .asomotor center' and the area
postrema) can either increase or decrease /P
7) Perip'eral Autoregulatory 1omponents:
1. Aenal
2. =ocal o:ygen tension
.) 8ascular $not'elial Mec'anisms: a de%iciency in the local
synthesis o% .asodilating s"*stances (prostacyclin and
*rady7inin' nitric o:ide) or e:cess .asoconstricting
s"*stances (angiotensin >> and endothelin >)
+) $lectrolytes an Ot'er 1'emicals: Pop"lation)*ased
st"dies indicate that high salt diets are associated ?ith a
high pre.alence o% stro7e and hypertension.
4ome st"dies sho? that dietary calci"m s"pplementation
res"lts in a modest /P red"ction in patients ?ith H!-.
Potassi"m (Potassi"m depletion may increase peripheral
.asc"lar resistanceP)
19
1lassification of BP 9 :#1-
!he ,-C0 classi%ication o% /P in ad"lts (age 18 years) is base on t'e average o%
t?o or more properly meas"red seated /P readings %rom t?o or more clinical
enco"nters
>t incl"des four categories# normal% pre'ypertension% stage 5 'ypertension% an
stage 6 'ypertension)
20
>% systolic and diastolic *lood press"re .al"es yield di%%erent classi%ications' the highest category is "sed %or
the p"rpose o% determining a classi%ication.
Prehypertension is not considered a disease category' *"t identi%ies patients ?hose /P is li7ely to increase
into the classi%ication o% hypertension in the %"t"re.
8or certain patients' /P .al"es ?ithin the prehypertension range are considered a*o.e goal.
2ypertensive crises
2ypertensive crises are clinical sit"ations ?here
/P .al"es are .ery ele.ated' typically greater than
1805110 mm Hg.
Hypertensi.e crisis can *e di.ided into#
5) 2ypertensive emergencies are e:treme ele.ations in
/P that are accompanied *y ac"te or progressing
target)organ damage.
6) 2ypertensive urgencies are high ele.ations in /P
?itho"t ac"te or progressing target)organ in@"ry.
21
1ariovascular Ris3 an Bloo Pressure
Ais7 o% stro7e' myocardial in%arction' angina' heart %ail"re'
7idney %ail"re' or early death %rom a C; ca"se are irectly
correlate (it' BP.
4tarting at a /P o% 112502 mm Hg' ris7 o% C; disease
do"*les ?ith e.ery 20510 mm Hg increase.
E.en patients ?ith prehypertension ha.e an increased ris7
o% C; disease.
!reating patients ?ith hypertension ?ith antihypertensi.e
dr"g therapy pro.ides signi%icant *ene%its.
22
1ariovascular Ris3 an Bloo Pressure
4/P is a stronger predictor o% C; disease than &/P in
ad"lts older than 20 years o% age and is the most
important clinical /P parameter %or most patients.
Patients (it' ;solate systolic 'ypertension (&/P .al"es
less than 90 mm Hg and 4/P .al"es Q140 mm Hg) ha.e
higher p"lse press"re .al"es.
>n these patients pathophysiologic changes in their
arterial .asc"lat"re are consistent ?ith aging. !hese
changes decrease the compliance o% the arterial ?all and
R ris7 o% C; mor*idity and mortality.
23
1linical Presentation of 2ypertension
<eneral
!he patient may appear .ery healthy' or may ha.e the presence o%
additional C; ris7 %actors#
1. ge ( 22 years %or men and 32 years %or ?omen)
2. &ia*etes mellit"s
+. &yslipidemia (ele.ated lo?)density lipoprotein)cholesterol' total cholesterol'
and5or triglycerides; lo? high)density lipoprotein)cholesterol)
4. 1icroal*"min"ria
2. 8amily history o% premat"re C; disease
3. B*esity (*ody mass inde: +0 7g5m
2
)
0. Physical inacti.ity
8. !o*acco "se
Symptoms
1ost patients are asymptomatic. =silent 3iller=
Signs
Pre.io"s /P .al"es in the prehypertension or hypertension category.
24
Diagnostic $valuation of BP
Diagnostic proceures aim at:
1. esta*lishing *lood press"re le.els;
2. identi%ying secondary ca"ses o% hypertension;
+. e.al"ating the o.erall cardio.asc"lar ris7 *y searching %or other
ris7 %actors' target organ damage and concomitant diseases or
accompanying clinical conditions.
T'e iagnostic proceures comprise:
9 repeated *lood press"re meas"rements
9 medical history (%amily and clinical)
9 physical e:amination
9 la*oratory and instr"mental in.estigations.
25
50 Measuring bloo pressure
>n general the diagnosis o% hypertension sho"ld *e *ased on m"ltiple
*lood press"re meas"rements (2) ' ta7en on separate occasions (2)+) o.er
a period o% time' altho"gh in partic"larly se.ere cases the diagnosis can
*e *ased on meas"rements ta7en at a single .isit.
/lood press"re can *e meas"red *y a merc"ry sphygmomanometer or
other non)in.asi.e de.ices (a"sc"ltatory or oscillometric semia"tomatic
de.ices).
o%%ice)*ased /P meas"rements are considered the gold standard .al"es
that g"ide antihypertensi.e dr"g therapy.
Correct /P meas"rements reC"ire that the clinician listen thro"gh a
stethoscope that is placed o.er the *rachial artery %or the appearance o%
the %i.e phases o% the (orot7o%% so"nds
26
27
Recommenations for measuring BP
Patients sho"ld re%rain %rom nicotine or ca%%eine ingestion %or +0 min"tes and *e seated
?ith the lo?er *ac7 s"pported in a chair and ?ith their *are arm s"pported and resting
near heart le.el.
8eet sho"ld *e %lat on the %loor (?ith legs not crossed).
1eas"ring /P in the s"pine or standing position may *e reC"ired "nder special
circ"mstances (s"spected orthostatic hypotension' .ol"me depletion' or dehydration).
!he meas"rement en.ironment sho"ld *e relati.ely C"iet and pro.ide pri.acy.
1eas"rement sho"ld *egin only a%ter a 2)min"te period o% rest.
properly siJed c"%% (pediatric' small' reg"lar' large' or e:tra large) sho"ld *e "sed.
29
P'ases of t'e >orot3off souns 'ear ('en inirectly
measuring bloo pressure)
Virtual_Sphyg[1].swf
Ambulatory an self bloo pressure monitoring
Either o% these may *e ?arranted in patients ?ith s"spected ?hite coat
hypertension (?itho"t hypertension)related target)organ damage) to
di%%erentiate ?hite coat %rom essential hypertension.
!hey may *e help%"l in patients ?ith#
apparent dr"g resistance'
hypotensi.e symptoms ?hile on antihypertensi.e therapy'
episodic hypertension'
a"tonomic dys%"nction' 5and
to identi%y SnondippersS ?hose /P does not decrease *y Q10I d"ring sleep and ?hich
may portend increased ris7 o% /P)related complications
As a comparison% t'e normal upper limit for BP in most patients is:
140590 mm Hg %or o%%ice)*ased meas"rement'
1+0580 mm Hg %or /P1 (1+2582 mm Hg ?hile a?a7e and 120502 mm Hg ?hile
asleep)'
1+2582 mm Hg %or sel%)/P meas"rements.
-ote#
the threshold %or accepta*le .al"es is lo?er than that o*tained d"ring o%%ice)*ased
meas"rements
30
1ain indications %or am*"latory /P monitoring are %or
patients in ?hom the diagnosis o% hypertension or response
to therapy is "nclear %rom o%%ice .isits. 8"rther indications
incl"de s"spected syncope or hypotensi.e disorders'
e.al"ation o% .ertigo' and diJJiness.
m*"latory /P monitoring is also important %or a.oiding
o.ertreatment in the elderly ?ith ?hite)coat hypertension
and also to ens"re diagnosis and treatment o% those ?ith
mas7ed hypertension
m*"latory /P is a *etter predictor o% ris7 than clinic or
o%%ice /P meas"rement in older patients ?ith isolated
systolic hypertension
31
Pseuo'ypertension
Pse"dohypertension is ?hen *lood press"re meas"rements
are ele.ated *"t the *lood press"re is act"ally normal.
Pse"dohypertension is not .ery common' and it is almost
al?ays %o"nd in older patients !/2?@"
Pseuo'ypertension is usually suspecte in cases ('ere:
!he *lood press"re reading is .ery high o.er time' *"t the
patient has no signs o% organ damage or other complications
ttempting to treat the meas"red high *lood press"re ca"ses
symptoms o% lo? *lood press"re (diJJiness' con%"sion'
decreased "rine o"tp"t)
Fhile a %inger *lood press"re meter or other similar de.ices
may pro.ide some "se%"l data in cases o% s"spected
pse"dohypertension' the only ?ay to con%irm the diagnosis
is *y directly meas"ring the intraarterial bloo pressure)
!his is done inserting a needle directly into a small artery.
32
T'e 1oncept of /'ite 1oat an
Mas3e 2ypertension
Office SBP mmHg
H
o
m
e
/
A
m
b
u
l
a
t
o
r
y

S
B
P

m
m
H
g
True
hypertensive
True
Normotensive
White Coat HTN
as!e" HTN
True
Normotensive
as!e" HTN
True
hypertensive
#$$
%&$
%'$
%($
%#$
%$$
%$$ %#$ %($ %'$ %&$ #$$
%)*
Masked HTN:
people who are truly
hypertensive but in
whom the diagnosis
is missed by office
BP measurements.
White-coat HTN:
BP may be elevated
in the office but not
on ambulatory BP
Resistant 2T#
Aesistant
hypertension is
de%ined as that in
?hich patients %ail
to attain their /P
goal ?hile treated
?ith a three)dr"g
regimen that "tiliJes
%"ll (ma:im"m)
antihypertensi.e
doses' one o% ?hich
is a di"retic.
34
Diagnostic algorit'm for 'ig' Bloo Pressure incluing
Office% ABPM an 2ome Bloo Pressure Measurement
BP: 140-179 / 90-109
ABPM (If available) Clinic BPM HBPM
Yes
Hypertension Visit 2
Target Organ Damage
or Diabetes
or Chronic Kidney Disease
or BP 180/110?
Hypertension Visit 1
BP Measurement,
History and Physical
examination
Hypertensive
Urgency /
Emergency
Diagnosis
of HTN
No
In the absence of end-organ
damage, the diagnosis of
mild hypertension should
not be made until the blood
pressure has been measured
on at least three to six visits,
spaced over a period of
weeks to months.
Diagnostic algorit'm for 'ig' Bloo Pressure incluing
Office% ABPM an 2ome Bloo Pressure Measurement
BP: 140-179 / 90-109
ABPM (If available)
Clinic BP
HBPM
Diagnosis
of HTN
Awake BP
135 SBP or
85 DBP
Or 24-hour
130 SBP or
80 DBP
Awake BP
< 135/85 and
24-hour
< 130/80
Continue to
follow-up
Diagnosis
of HTN
Hypertension visit 3
160 SBP or
100 DBP
140 SBP or
90 DBP
< 140 / 90
Diagnosis
of HTN
Continue to
follow-up
< 160 / 100
Hypertension visit 4-5
ABPM or HBPM
or
135
SBP or
DBP 85
< 135/85
Diagnosis
of HTN
Continue to
follow-up
or
1linical $valuation !1ont4"
Once it 'as been etermine t'at t'e patient 'as persistent
'ypertension% an evaluation s'oul be performe to ascertain t'e
follo(ing information:
!o determine the e:tent o% target organ damage.
!o assess the patientKs o.erall cardio.asc"lar ris7 stat"s.
!o r"le o"t identi%ia*le and o%ten c"ra*le ca"ses o%
hypertension.
37
60 <uielines for family an clinical 'istory !$S1"
comprehensi.e %amily history sho"ld *e o*tained ?ith partic"lar
attention to hypertension' dia*etes' dyslipidaemia' premat"re
coronary heart disease' stro7e' peripheral artery or renal disease.
70 <uielines for p'ysical e&amination !$S1"
Courtesy J.P. Desprs 2006
Mid distance
Last rib margin
Iliac crest
/aist 1ircumference Measurement
.0 Laboratory investigations !$S1"
!he patient may ha.e normal .al"es and still ha.e hypertension. Ho?e.er' some may ha.e
a*normal .al"es consistent ?ith either additional C; ris7 %actors or H!-)related damage.
1omments on 1linical $valuation
1any g"idelines ad.ocate Tro"tine la*oratory testingU in
e.al"ation o% patients ?ith high /P. &espite s"ch
recommendations' there is little e.idence to s"pport ro"tine
la*oratory testing' and clinicians sho"ld ta7e a more deli*erati.e
and reasoned approach to ordering tests. Ao"tine testing
increases costs and may ha.e ad.erse e%%ects s"ch as an:iety'
pain5discom%ort' additional testing' complications %rom s"ch
testing' and time and tra.el *"rden.
!he most important role %or testing in an elderly patient ?ith
hypertension is to assess %or organ damage and modi%ia*le C;&
ris7 %actors' incl"ding to*acco smo7ing' hypercholesterolemia'
dia*etes mellit"s' and e:cessi.e alcohol inta7e.
45
2ypertension Management !<oals"
Hypertension is treated ?ith *oth lifestyle moifications and
p'armacot'erapy.
!he presence o% speci%ic complications o% hypertension or comor*idities
(sometime re%erred to as Tcompelling inicationsU) in any gi.en patient
sho"ld *e considered ?hen selecting speci%ic pharmacotherapy to treat
hypertension.
!he overall goal of treating 'ypertension is to red"ce associated
mor*idity and mortality. !hese mani%est as hypertension)associated
complications ?hich are the primary ca"ses o% death in patients ?ith
hypertension.
the speci%ic choice o% dr"g therapy is signi%icantly in%l"enced *y e.idence
demonstrating s"ch ris7 red"ction.
Surrogate goal of t'erapy is to achie.e a desired target /P .al"e
46
2ypertension0Associate 1omplications
At'erosclerotic 8ascular Disease:
Coronary artery5heart disease
1yocardial in%arction L1>M
c"te coronary syndromes
Chronic sta*le angina
Carotid artery disease#
>schemic stro7e
!ransient ischemic attac7
Peripheral arterial disease
*dominal aortic ane"rysm
Ot'er forms of 18 isease
=e%t .entric"lar dys%"nction (heart %ail"re)
1'ronic 3iney isease
47
Ris3 factors for 'ypertension0associate complications
T'ese are consiere major 18 ris3 factors t'at increase t'e li3eli'oo of
eveloping 'ypertension0associate complications% not 'ypertension)
/1>' *ody mass inde:; C;' cardio.asc"lar; 68A' glomer"lar %iltration rate.
48
Hypertension
Cigarette smo7ing
B*esity (/1> Q+0 7g5m2)
Physical inacti.ity
&yslipidemia
&ia*etes mellit"s
(idney disease
1icroal*"min"ria or
estimated 68A V 30 ml5min
d.anced age
1ales Q 22 yrs
8emales Q 32 yrs
8amily history o% premat"re
atherosclerotic .asc"lar disease
1ales V 22 yrs
8emales V 32 yrs
,raming'am Ris3 Scoring
$stimating iniviual ris3 for 18 isease is essential for all patients (it'
'ypertension)
,raming'am ris3 scoring is considered an appropriate ?ay to predict indi.id"al
10)year ris7 %or coronary artery disease (C&)' &yslipipidemias' therosclerosis'
and Coronary Heart &isease).
ll patients ?ith hypertension ?ho do not ha.e a history o% hypertension)
associated complications or dia*etes' (considered a C& ris7 eC"i.alent
condition) sho"ld ha.e 8ramingham ris7 scoring *eca"se their 10)year ris7 can
*e#
lo( or moerate ris3 !A5BC"%
moerately 'ig' ris3 !5BC96BC"% or
'ig' ris3 !D6BC")
;entifying patients (it' ,raming'am ris3 scores E5BC is clinically relevant
because more aggressive anti'ypertensive treatment is neee in t'is
population.
8or patients ?ith hypertension)associated complications or dia*etes'
8ramingham ris7 scoring is not needed *eca"se 10)year ris7 o% C& is ass"med to
*e Q20I.
49
,raming'am Point Scale for $stimating 5B0?ear 12D
Ris3 if D 6 ris3 factors !MenF/omen"
51
<oal BP etermination
base on patient specific
'istory an cariovascular
ris3 assessment !A2A 6BB-"
2ome(or3
Fhat is the ,)c"r.e phenomenonP
52
Benefits of Lo(ering BP
Fhy treat H!-P
+2)40I in stro7e mor*idity and mortality
20)22I C& e.ents
21I .asc"lar mortality
22I in CH8
+2I in =;H
53
<eneral Approac' to Treatment
li%estyle modi%ications
dr"g therapy
!he choice o% initial dr"g therapy depends on the
degree o% /P ele.ation and presence o% compelling
indications.
54
55
Dietary Approaches to
Stop Hypertension
The effects of implementing these
modifications are dose and time
dependent, and could be greater for
some individuals.
For overall
cardiovascular risk
reduction, stop smoking.
Dietary Soium
=ess than 2+00mg 5 day
(1ost o% the salt in %ood is Whidden<
and comes %rom processed %ood)
Dietary Potassium
&aily dietary inta7e Q80 mmol
1alcium supplementation
-o concl"si.e st"dies %or hypertension
Magnesium supplementation
-o concl"si.e st"dies %or hypertension
Lifestyle Recommenations for 2ypertension:
Dietary
2ig' in:
X8resh %r"its
X8resh .egeta*les
X =o? %at dairy prod"cts
X&ietary and sol"*le
%i*re
XPlant protein
Lo( in:
X4at"rated %at and
cholesterol
X4odi"m
;ncrease Potassium ;nta3e
ne? recommendation %rom the H is to increase dietary potassi"m
inta7e.
dhering to a &4H eating plan ?ill "s"ally ass"re an inta7e o% the
recommended 4.0 g daily.
>mplementing potassium supplementation o"tside o% dietary so"rces %or
the sole p"rpose o% lo?ering /P s'oul be avoie *eca"se o% potential
harm %rom hyper7alemia.
1oreo.er' potassi"m s"pplementation in patients ?ith hypertension ?ho
are treated ?ith either a potassi"m)sparring di"retic' aldosterone
antagonist' angiotensin)con.erting)enJyme inhi*itors (CE>)' or an
angiotensin receptor *loc7er (A/) may ca"se hyper7alemia.
!his can also occ"r in patients ?ith hypertension and chronic 7idney
disease ?ho are treated ?ith potassi"m s"pplementation.
http://www.nhlbi.nih.gov/guidelines/hypertension/index.htm
Lifestyle Recommenations for 2ypertension:
/eig't Loss
Height' ?eight' and ?aist circ"m%erence (FC) sho"ld *e meas"red and *ody
mass inde: (/1>) calc"lated %or all ad"lts.
Hypertensive and all patients
BMI over 25
- Encourage weight reduction
- Healthy BMI: 18.5-24.9 kg!
2
Waist Circumference Men Women
- Euro"id# $u%-$aharan &'rican# Middle Ea(tern )94 c! )8* c!
- $outh &(ian# +hine(e# ,a"ane(e )9* c! )8* c!
-or "atient( "re(cri%ed "har!acological thera"y: weight lo(( ha(
additional antihy"erten(i.e e''ect(. /eight lo(( (trategie( (hould
e!"loy a !ultidi(ci"linary a""roach and include dietary education#
increa(ed "hy(ical acti.ity and %eha.iour !odi'ication
CMAJ 2007;176:1103-6
Exercise should be prescribed as an adjunctive to pharmacological
therapy
Lifestyle Recommenations for 2ypertension:
P'ysical Activity
Should be prescribed to reduce blood pressure
Type Cardiorespiratory Activity
- Walking, jogging
- Cycling
- Non-competitive swimming
Time - 30-60 minutes
Intensity - Moderate
Frequency - Four to seven days per week
F
I
T
T
Lifestyle Recommenations for 2ypertension:
Alco'ol
Low risk alcohol consumption
Women: maximum of 9 standard drinks/week
Men: maximum of 14 standard drinks/week
0-2 standard drinks/day
A standard drink is about 142 ml or 5 oz of wine (12% alcohol). 341 mL or 12 oz of
beer (5% alcohol) 43 mL or 1.5 oz of spirits (40% alcohol).
Lifestyle Recommenations for 2ypertension:
Stress Management
Hy"erten(i.e "atient(
in who! (tre(( a""ear( to %e an i!"ortant i((ue
Indi.iduali0ed cogniti.e %eha.ioural
inter.ention( are !ore likely to %e
e''ecti.e when rela1ation techni2ue(
are e!"loyed.
Beha.iour Modi'ication
s'oul lifestyle moifications be t'e primary
treatment@
=i%estyle modi%ications are germane to the appropriate
treatment o% hypertension' *"t they ha.e not *een
sho?n to pre.ent C; disease in patients ?ith
hypertension.
s recommended in the H and the E4C g"idelines
%rom 2000' initiation o% dr"g therapy sho"ld not *e
delayed "nnecessarily' especially %or patients ?ith C;
ris7 %actors.
62
P'armacological management of
2ypertension
1any effective rugs are a.aila*le.
1ost antihypertensi.e dr"gs lo?er
*lood press"re *y red"cing cardiac
o"tp"t and5or decreasing peripheral
resistance.
>no(lege o% their antihypertensi.e
mechanisms and sites o% action allo?s
acc"rate prediction o% e%%icacy and
to:icity.
rational use o% these agents' alone or in
com*ination' can lo?er *lood press"re
?ith minimal ris7 o% serio"s to:icity in
most patients.
1ategories of anti2T# rugs:
!5" Diuretics 9 rugs t'at alter soium G (ater balance: H/P *y depleting *ody o% -a Y
Z *lood .ol"me Y perhaps *y other mechanisms.
!6" Sympat'oplegic agents 9 red"ce the e%%ect o% the sympathetic ner.o"s system# Z/P
*y Z P;A' inhi*i[ng cardiac %"nc[on' Y R .eno"s pooling in capacitance .essels. (!he
latter 2 e\ects Z CB). !hese agents are %"rther s"*di.ided.
Centrally acting sympathoplegic dr"gs
6anglion)*loc7ing agents (o*solete)
Postganglionic sympathetic ner.e terminal *loc7ers
drenoceptor *loc7ers
PraJosin Y other alpha
1
*loc7ers
/eta *loc7ers
!7" Direct vasoilators% ?hich Z press"re *y rela:ing .asc"lar smooth m"scle ]dilate
resistance .essels R capacitance as ?ell.
Bral .asodilators
Calci"m channel *loc7ers
Parenteral .asodilators
!." Agents t'at bloc3 prouction or action of angiotensin ]Z P;A Y (poten[ally) *lood
.ol"me.
ngiotensin)con.erting enJyme (ace) inhi*itors
ngiotensin receptor)*loc7ing agents
P'armacot'erapy:
Primary agents
iuretic (primarily a thiaJide)type)' A1$ in'ibitor(CE)>)'
angiotensin ;; receptor bloc3er (A/)' or calcium c'annel
bloc3er (CC/) are considered primary
!hese agents sho"ld *e "sed to treat the ma@ority o% patients
?ith hypertension *eca"se e.idence %rom o"tcomes data ha.e
demonstrated C; ris7 red"ction *ene%its ?ith these classes.
4e.eral ha.e s"*classes ?here signi%icant di%%erences in
mechanism o% action' clinical "se' side e%%ects' or e.idence %rom
o"tcomes st"dies e:ist.
B 0Bloc3ers are e%%ecti.e antihypertensi.e agents that
pre.io"sly ?ere considered primary agents.
!hey are no? pre%erred either to treat a speci%ic compelling
indication' or in com*ination ?ith one o% the a%orementioned
primary antihypertensi.e agents %or patients ?itho"t a
compelling indication.
65
Diuretics
Fell st"died# Class o% agents %or H!- "se%"l in Heart 8ail"re
=o? acC"isition cost' cost e%%ecti.e
Pro.en mortality *ene%it in hypertension
E%%ecti.e in ?hites and %rican mericans
Mec'anism# &ecrease P;A in the long term
Monitor for# Hypo7alemia (lo? potassi"m)' hyper"racemia'
hyperglycemia' hypercalcemia' ad.erse lipid e%%ects'
gynecomastia (spirionlactone)
Fhich gentP (!hiaJides or =oops)
ClCr Q +0 ml5min thiaJide (all pro*a*ly ?or7 eC"ally ?ell)
ClCr V +0 ml5min loop di"retics or com*ination
66
67
68
69
70
71
72
73
74
75
A1$ ;n'ibitors
Practical note#
>nitiate ?ith small doses
Contin"e %or 2)4 ?ee7s *e%ore assessing *ene%its
1ay ta7e +)3 months %or ma:im"m *ene%it (H8) *"t 1)2 months %or H!-
Mec'anism# /loc7 con.ersion o% ngiotensin > to angiotensin >> and *loc7s
*rea7do?n o% *rady7inin (.asodilator)
Sie $ffects#
Hypotension (monitor /P)
Aenal >ns"%%iciency (monitor 4cr)
Potassi"m retention (monitor ()
Co"gh (especially in ?omen and elderly)
Aare# angioedema
Contraindicated in A4 and angioedema
>ey option for dia*etics (?ith nephropathy)' patients ?ith heart %ail"re'
myocardial in%arction
&ecreased e%%icacy in older %rican mericans.
76
Angiotensin ;; Receptor Bloc3ers !ARBs"
4imilar anti)H!- e%%icacy to CE inhi*itors and atenolol
(perhaps less 4E<s and &5C rates)
-ot in%erior to CE<s %or o"tcomes (B-!A6E! -E,1
2008)
d.antages may *e in red"ced incidence o% co"gh and
angioedema (.s. CE inhi*itors) altho"gh angioedema has
*een reported
pparently no e%%ects on lipids' %asting gl"cose altho"gh
ha.e a signi%icant "ricos"ric e%%ect
Hyper7alemia can occ"r to compara*le le.el as ?ith CE
inhi*itors
77
78
79
80
81
82
1omments on t'e previous table
83
1alcium 1'annel Bloc3ing Agents !11B4s"
Mec'anism# red"ce cardiac ?or7 *y negati.e
chronotropic (heart rate)' negati.e inotropic (contractility)
and systemic .asodilation (rela: sm. m"scles o% arterioles)
P'armacologic ;ssues# relati.e e%%ects on cond"ction
system' negati.e inotropism' .asodilatation
Monitor# HA' /P' EC6' P()P& interaction ?ith dr"gs.
;ssues# Edema ?ith higher doses o% dihydropriydines'
C^P+4 inhi*ition o% .erapamil5diltiaJemP
84
85
87
B0Bloc3ers
Mec'anism# red"ce cardiac ?or7 *y negati.e inotropic' negati.e
chronotropic and hypotensi.e (central and renin *loc7ing) e%%ects
P'armacologic ;ssues# &i.erse gro"p# %irst pass e%%ect' modest hal%)li%e'
.aria*le protein *inding' cardioselecti.ity (dose dependent)' intrinsic
sympathomimetic acti.ity' alpha)*loc7ade
Monitor# 4E<s are e:tension o% pharmacologic e%%ects' *radycardia'
hypotension' depression' impotence' dia*etes (*loc7 signs and symptoms
o% hypoglycemia)' reacti.e air?ay disease' ad.erse lipid e%%ects (decrease
H&=' increase !6) ' a*r"pt ?ithdra?al.
Clinical trials ha.e sho?n signi%icant cardio.asc"lar mor*idity and
mortality *ene%its in non)elderly
1omments# $se%"l ?ith select comor*idities e.g. ischemic heart disease'
(angina' myocardial in%arction)' heart %ail"re' ho?e.er ha.e recently *een
considered less %a.ora*le .s. other options %or some patients (1eta)
analysis# =indholm=ancet 2002;+42#1242)2+ )
88
89
90
/eta *loc7ers ha.e *een "sed %or hypertension' *"t e.idence %or
a *ene%it in the elderly has not *een con.incing. !hey may ha.e a
role in com*ination therapy' especially ?ith di"retics. /eta
*loc7ers are indicated in the treatment o% elderly patients ?ho
ha.e hypertension ?ith C&' H8' certain arrhythmias' migraine
headaches' and senile tremor. ltho"gh earlier *eta *loc7ers
ha.e *een associated ?ith depression' se:"al dys%"nction'
dyslipidemia' and gl"cose intolerance' these side e%%ects are less
prominent or a*sent ?ith ne?er agents.
alpha)*eta *loc7ers are important in hypertensi.e "rgencies
(la*etalol) and congesti.e H8 (car.edilol).
!here<s a higher ris7 o% orthostatic hypotension ?ith these
agents.
Car.edilol (>A and 4A) m"st *e ta7en ?ith %ood. Car.edilol is only
a.aila*le orally.
91
P'armacot'erapy:
Alternative agents
>t is necessary to "se other agents s"ch as I0bloc3ers% central a60
agonists% a irect renin in'ibitor !Alis3iren"% arenergic in'ibitors
!Reserpine"% an vasoilators !Mino&iil% 2yralaJine" in some
patients.
these agents are potent'
many o% them ha.e a m"ch greater incidence o% ad.erse e%%ects.
they do not ha.e compelling o"tcomes data sho?ing red"ced
mor*idity and mortality in hypertension.
!hey are generally reser.ed %or patients ?ith resistant
hypertension' and sho"ld only *e "sed as add)on therapy ?ith
other primary antihypertensi.e agents.
92
93
Alp'a50Bloc3ers
Agents#
&o:aJosin (Card"ra_)' PraJosin (1inipress_)' !eraJosin (Hytrin_)' !ams"losin
(8loma:_)
Avantages
$se%"l in patients ?ith dyslipidemia# ne"tral or *ene%icial e%%ect on lipids
$se%"l in patients ?ith hypertension and *enign prostatic hypertrophy
Disavantages
Can prod"ce %irst dose syncope
Common 4Es (2)20I)# &iJJiness' headache' lethargy' palpitations
Brthostatic hypotension can occ"r
Early termination o% do:aJocin arm o% ==H! d"e to negati.e o"tcome
(higher H8' stro7e' C;& ris7) o% do:aJocin .s. chlorthalidone (,1
2000#28+;1930)02)
94
Alis3iren
Bral direct plasma renin inhi*itor ?hich decreases
plasma renin acti.ity *y inhi*iting con.ersion o%
angiotensinogen to ng 1
ppro.ed %or H!- (alone or in com*ination)
P># *sorption "n7no?n' Cma: ?ithin 1)+ hrs' $C
decreased *y 00I ?ith high %at meals' 22I eliminated
"nchanged' some C^P+4 meta*olism
;ssues# Contraindicated in pregnancy' angioedema
potential' co"gh V CE inhi*itors *"t early
Dose# 120mg5once daily "p to +00mg5d
95
1entrally acting alp'a60Agonists
Agents#
Clonidine (Catapress_)' 6"ana*enJ ' 6"an%acine' 1ethyldopa
(ldomet_)
Avantages
Clonidine# .ery C"ic7 onset and "se%"l %or hypertensi.e "rgencies
Clonidine# as a patch is applied once a ?ee7 impro.ing adherence
1ethyldopa is a "se%"l antihypertensi.e d"ring pregnancy
Disavantages
1any %reC"ent (2)40I) 4Es limit the "se o% these agents (e.g. &ry
mo"th' dro?siness' diJJiness' constipation' ?ea7ness' na"sea Y
.omiting' agitation' orthostatic hypotension)
*r"pt ?ithdra?al o% therapy res"lts in a rapid (24)48hr) re*o"nd
hypertension
96
Perip'erally Acting Arenergic Bloc3ers
Agents:
6"anadrel' 6"anethidine' Aeserpine
Avantages
Aeserpine is generally ?ell tolerated at lo? doses
=o? Cost
Disavantages
Common 4Es (2)40I) %or 6"anadrel' 6"anethidine# signi%icant
orthostatic hypotension' syncope' diarrhea' dro?siness' %atig"e'
decreased e@ac"lation' peripheral edema' nasal st"%%iness' co"gh'
palpitations' 4B/' leg cramps
Aeserpine 4Es# -asal congestion' acti.ation o% P$& .oid in P$&
patients. Possi*le dose related depression .oid in patients ?ith
depression history
97
Direct 8asoilators
Agents:
HydralaJine' 1ino:idil
Avantages
/oth are potent .asodilators
HydralaJine >; is a sa%e choice %or eclampsia
1ino:idil co"ld *e added to a regimen in case o% a resistant
hypertension
Disavantages
1ino:idil 4Es# Hirs"tism' transient EC6 (! ?a.e) changes
HydralaJine common 4Es# Headache' na"sea 5 .omiting'
diarrhea'
Ae%le: tachycardia and A4 acti.ation %or *oth
98
1ombination Drug T'erapy
99
Notes:
Treatment is determined by highest BP category.
Initial combined therapy should be used cautiously in those at risk
for orthostatic hypotension.
Drug 1ombinations
Fhen com*ining dr"gs' "se %irst)line therapies.
!?o dr"g com*inations o% *eta *loc7ers' CE inhi*itors and angiotensin
receptor *loc7ers ha.e not *een pro.en to ha.e additi.e hypotensi.e
e%%ects. !here%ore these potential t?o dr"g com*inations sho"ld not *e
"sed "nless there is a compelling (non *lood press"re lo?ering) indication
Com*inations o% an CE> ?ith an A/ do not red"ce cardio.asc"lar e.ents
more than the CE> alone and ha.e more ad.erse e%%ects there%ore are
not generally recommended
Ca"tion sho"ld *e e:ercised in com*ining a non dihydropyridine CC/ and
a *eta *loc7er to red"ce the ris7 o% *radycardia or heart *loc7.
1onitor ser"m creatinine and potassi"m ?hen com*ining ( sparing
di"retics' CE inhi*itors and5or angiotensin receptor *loc7ers.
>% a di"retic is not "sed as %irst or second line therapy' triple dr"g therapy
sho"ld incl"de a di"retic' ?hen not contraindicated.
Preferred: fully additive effects
Acceptable: Partially additive
Less effective: little or no additional
reduction in BP
102
103
104
105
106
107
;nitiation of Drug T'erapy 9 #o 1ompelling ;nications
!he initial antihypertensi.e dr"g sho"ld *e starte at t'e lo(est ose an
graually increase epening on t'e BP response to t'e ma&imum
tolerate ose)
>% the antihypertensi.e response to the initial dr"g is inadeC"ate a%ter reaching
full ose !not necessarily ma&imum recommene ose"% a secon rug
from anot'er class s'oul be ae% pro.ided the initial dr"g is tolerated.
>% the person is ha.ing no therape"tic response or signi%icant ad.erse e%%ects' a
dr"g %rom another class sho"ld *e s"*stit"ted. ;f a iuretic is not t'e initial
rug% it is usually inicate as t'e secon rug)
>% the antihypertensi.e response is inadeC"ate a%ter reaching the %"ll dose o% 2
classes o% dr"gs' a third dr"g %rom another class sho"ld *e added.
/'en t'e BP is 6BF5B mm 2g above goal% rug t'erapy s'oul generally be
initiate (it' 6 anti'ypertensive rugs% one of ('ic' s'oul be a t'iaJie
iuretic; ho?e.er' in the elderly' treatment m"st *e indi.id"aliJed
Choice o% antihypertensi.e agent may *e less important than getting to *lood
press"re goal.
/e%ore adding ne? antihypertensi.e dr"gs' possi*le reasons %or inadeC"ate /P
response sho"ld *e e:amined.
108
1onsierations in primary anti'ypertensive rug c'oice
Antihypertensive
Agent
Situations with
Potentially Favorable
Effects
Situations with
Potential Unfavorable
Effects Avoid Use
CE> =o?)normal potassi"m'
predia*etes'
microal*"min"ria in
patients ?itho"t dia*etes
High)normal
potassi"m or
hyper7alemia
Pregnancy'
*ilateral renal
artery stenosis'
history o%
angioedema
A/ =o?)normal potassi"m'
predia*etes'
microal*"min"ria in
patients ?itho"t dia*etes
High)normal
potassi"m or
hyper7alemia
Pregnancy'
*ilateral renal
artery stenosis
!hiaJide di"retic Bsteoporosis or at
increased ris7 %or
osteoporosis' high)normal
potassi"m
6o"t' hyponatremia'
predia*etes (as
monotherapy)' lo?)
normal potassi"m
High)normal re%ers to patients in the high end o% the normal range' *"t not a*o.e the range.
=o?)normal re%ers to patients in the lo? end o% the normal range' *"t not *elo? the range.
1O#T4D
109
Antihypertensive
Agent
Situations with
Potentially Favorable
Effects
Situations with
Potential Unfavorable
Effects Avoid Use
CC/#
dihydropyridine
Aayna"dKs syndrome'
elderly patients ?ith
isolated systolic
hypertension'
cyclosporine ind"ced
hypertension
Peripheral edema' le%t
.entric"lar dys%"nction
(all e:cept amlodipine
and %elodipine)' high)
normal heart rate or
tachycardia
CC/#
nondihydropyridine
Aayna"dKs syndrome'
migraine headache'
arrhythmias' high)
normal heart rate or
tachycardia
Peripheral edema' lo?)
normal heart rate
4econd or third
degree heart
*loc7' le%t
.entric"lar
dys%"nction
110
Think about:
The costs: affordable regimens that do not compromise efficacy should
be designed. Generic antihypertensive products are less expensive than
brand-name products.
The frequency of administration: since it can influence patients'
adherence to regimens.
1ontrainications
Treatment Algorit'm for ;solate Systolic 2ypertension (it'out
Ot'er 1ompelling ;nications
INITIAL TREATMENT AND MONOTHERAPY
Thiazide diuretic
Long-acting
DHP CCB
Lifestyle modification
therapy
ARB
TARGET <140 mmHg
The reason that an ACE
inhibitor is not included
is due to the lack of
randomized controlled
trials with hard clinical
outcomes in patients
with isolated systolic
hypertension.
CONSIDER
Nonadherence
Secondary HTN
Interfering drugs or
lifestyle
White coat effect
If partial response to monotherapy
Triple therapy
Dual combination
Combine first line agents
If blood pressure is still not controlled, or there are adverse effects,
other classes of antihypertensive drugs may be combined (such as
ACE inhibitors, alpha adrenergic blockers, centrally acting agents, or
nondihydropyridine calcium channel blocker).
T'iaJie0type iuretics: a traitional first0line t'erapy
for most patientsK
:#1- guielines recommend thiaJide)type di"retics ?hene.er
possi*le' as %irst)line therapy %or most patients' ?hich is
consistent ?ith the traditional pharmacotherapy o%
hypertension.
Ho?e.er' A2A guielines do not recommend thiaJide)type
di"retics as pre%erred o.er an CE inhi*itor' A/' or CC/ %or %irst)
line therapy.
!reatment ?ith either an CE>' A/' CC/ or thiaJide di"retic is
considered accepta*le according to the most recent e.idence)*ased
g"idelines
!he *nite >ingom guielines strati%y patients *ased on age
and race; they recommend#
an CE inhi*itor %irst)line %or patients yo"nger than age 22 years' and
either a CC/ or thiaJide)type di"retic %irst)line %or patients age 22
years or older and %or *lac7 patients.
113
B0bloc3ers versus ot'er first0line rug t'erapies
Clinical trials data c"m"lati.ely s"ggests that O)*loc7ers may not
red"ce C; e.ents to the e:tent that CE inhi*itors' CC/s' or A/s
do. !hese data are %rom three meta)analyses o% clinical trials
e.al"ating /)*loc7er9*ased therapy %or hypertension.
$sing a O)*loc7er as a primary antihypertensi.e agent is optimal
?hen a thiaJide)type di"retic' CE inhi*itor' A/' or CC/ cannot *e
"sed as the primary agent.
$sing a O)*loc7er in a yo"ng patient ?ith hypertension that is
tho"ght to ha.e high adrenergic dri.e' as e.idenced *y an ele.ated
heart rate' may still *e clinically reasona*le.
O)/loc7ers still ha.e an important role as an alternati.e add)on
agent to red"ce /P in patients ?ith hypertension *"t ?itho"t
compelling indications.
114
Patients (it' 1ompelling ;nications
Compelling indications represent speci%ic comorbi conitions
?here e.idence %rom clinical trials s"pports "sing speci%ic
antihypertensi.e classes to treat *oth the compelling indication and
hypertension.
!he ,-C0 report identi%ies si& compelling inications.
&ata %rom clinical trials demonstrate a red"ction in C; mor*idity
and5or mortality that @"sti%ies "se in patients ?ith hypertension and
?ith s"ch a compelling indication.
4ome compelling indications incl"de recommendations that are
pro.ided *y other national treatment g"idelines' or %rom ne?er
clinical trials' ?hich are complementary to the ,-C0 g"idelines.
115
)2,
)Post0M;
)2ig' 1AD ris3
)DM
)1'ronic >iney Disease
)Recurrent stro3e Prevention
Treatment of 2ypertension in Patients (it' #on Diabetic
1'ronic >iney Disease
Chronic kidney
disease and
proteinuria *
ACEI/ARB:
Bilateral renal
artery stenosis
ACEI or ARB (if ACEI not tolerated)
Combination with other agents
Additive therapy: Thiazide diuretic.
Alternate: If volume overload: loop diuretic
Target BP: < 130/80 mmHg
* albumin:creatinine ratio [ACR] > 30 mg/mmol
or urinary protein > 500 mg/24hr
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB
+o!%ination( o' a &+EI and a &3B are ("eci'ically not reco!!ended in the a%(ence o' "roteinuria
Treatment of 2ypertension in association (it'
Diabetes Mellitus
More than 3 drugs may be needed to reach target values for diabetic patients
If Creatinine over 150 mol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should
be substituted for a thiazide diuretic if control of volume is desired
Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg
Diabetes
with
Nephropathy
> 2-drug
combinations
ACE Inhibitor
or ARB
without
Nephropathy
1. ACEInhibitor or
ARB
or
2. Thiazide diuretic
or DHP-CCB
Monitor (eru! "ota((iu! and creatinine care'ully in "atient( with +45 "re(cri%ed an &+EI or &3B
+o!%ination( o' an &+EI with an &3B are ("eci'ically not reco!!ended in the a%(ence o' "roteinuria
A combination of 2 first line
drugs may be considered as
initial therapy if the blood
pressure is >20 mmHg systolic
or 610 mmHg diastolic above
target
Treatment of 2ypertension
for Patients with 1erebrovascular Disease
$trongly con(ider %lood "re((ure reduction
in all "atient( a'ter the acute "ha(e o'
(troke or 7I& .
An ACEI / diuretic
combination is preferred
Stroke
TIA
Combinations of an ACEI with an ARB are not recommended
Treatment of 2ypertension in Patients with Recent ST
Segment $levation0M; or non0ST Segment $levation0M;
Long-acting
Dihydropyridine
CCB*
Beta-blocker and
ACEI or ARB
Recent
myocardial
infarction
Heart
Failure
?
NO
YES
Long-acting CCB
If beta-blocker
contraindicated or
not effective
*Avoid non dihydropyridine CCBs (diltiazem, verapamil)
Treatment of 2ypertension in Patients (it' ;sc'emic
2eart Disease
Caution should be exercised when combining a non DHP-CCB and a beta-blocker
If abnormal systolic left ventricular function: avoid non DHP-CCB (Verapamil or
Diltiazem)
Dual therapy with an ACEI and an ARB are not recommended in the absence of
refractory heart failure
The combination of an ACEi and CCB is preferred
1. Beta-blocker
2. Long-acting CCB
Stable angina
ACEI are recommended for most
patients with established CAD*
ARBs are not inferior to ACEI in IHD
Short-acting
nifedipine
*Those at low risk with well controlled risk factors may not benefit from ACEI therapy
Treatment of 2ypertension (it' Left 8entricular Systolic
Dysfunction
Beta-blockers used in clinical trials were bisoprolol, carvedilol and
metoprolol.
If additional therapy is needed:
Diuretic (Thiazide for hypertension; Loop for volume control)
for CHF class III-IV or post MI: Aldosterone Antagonist
Systolic
cardiac
dysfunction
ACEI and Beta blocker
if ACEI intolerant: ARB
Titrate doses of ACEI or ARB to those used in clinical trials
If ACEI and ARB are contraindicated: Hydralazine and Isosorbide
dinitrate in combination
If additional antihypertensive therapy is needed:
ACEI / ARB Combination
Long-acting DHP-CCB (Amlodipine)
Non
dihydropyridine
CCB
Special Populations:
5) 2ypertension in Oler People
red"ctions in C; mor*idity and mortality in older patients ?ith
isolated systolic hypertension' ?ith t'iaJie0type iuretics and
long0acting i'yropyriine 11Bs.
1entrally acting agents an alp'a50bloc3ers sho"ld generally *e
a.oided or "sed ?ith ca"tion in the elderly *eca"se they are
%reC"ently associated ?ith diJJiness and post"ral hypotension.
Diuretics an A1$ in'ibitors pro.ide signi%icant *ene%its and can
sa%ely *e "sed in the elderly' *"t smaller)than)"s"al initial doses
might *e needed.
initial rug oses may *e lo?er' and dosage titrations sho"ld occ"r
o.er a longer period o% time to minimiJe the ris7 o% hypotension.
n interim goal of a SBP o% *elo? 130 mm Hg may *e necessary %or
those ?ith .ery high initial 4/P' *"t the ultimate goal sho"ld still *e
less than 140 mm Hg' less than 1+0 mm Hg' or less than 120 mm
Hg' depending on C; ris7 and comor*id conditions o% the patient.
122
Special populations:
6) Patients at ris3 for ort'ostatic 'ypotension
Ort'ostatic 'ypotension is a signi%icant drop in /P ?hen standing
and can *e associated ?ith diJJiness and5or %ainting. >t is de%ined as
a 4/P decrease o% greater than 20 mm Hg or &/P decrease o%
greater than 10 mm Hg ?hen changing %rom s"pine to standing.
$se o% .enodilators (N )*loc7ers' mi:ed N5O)*loc7ers' nitrates' and
phosphodiesterase inhi*itors) increase ris7 o% orthostatic
hypotension.
>n patients ?ith these ris7s' antihypertensi.e agents sho"ld *e
starte in lo( oses' especially di"retics' CE inhi*itors' and A/s.
123
Special populations:
7) 2ypertension in c'ilren an aolescents
Define as: 4/P and5or &/P that is greater than 92
th
percentile %or se:' age' and
height on at least three occasions. /P *et?een the 90
th
and 92
th
percentile' or
eC"al to or greater than 120580 mm Hg in adolescents' is considered
prehypertension
4tage > hypertension is diagnosed i% a child<s /P is greater than the 92th percentile *"t less than
or eC"al to the 99th percentile pl"s 2 mm Hg. 4tage >> hypertension is diagnosed i% a child<s /P is
greater than the 99th percentile pl"s 2 mm Hg.
Seconary 'ypertension is more common in children and adolescents. n
appropriate ?or7"p %or secondary ca"ses is essential#
(idney disease (e.g.' pyelonephritis' glomer"lonephritis)
Coarctation o% the aorta
1edical or s"rgical management o% the "nderlying disorder "s"ally normaliJes
/P.
#onp'armacologic treatment' partic"larly ?eight loss in those ?ho are
o.er?eight.
CE inhi*itors' A/s' /)*loc7ers' CC/s' and thiaJide type di"retics are all
accepta*le choices in children.
s ?ith ad"lts' consideration %or initial agents sho"ld *e *ased on the presence
o% compelling indications.
124
125
SBP (mmHg) DBP (mmHg)
Age BP Percentile of Height Percentile of Height
(Year) Percentile 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
12 50th 102 103 104 105 107 108 109 61 61 61 62 63 64 64
90th 116 116 117 119 120 121 122 75 75 75 76 77 78 78
95th 119 120 121 123 124 125 126 79 79 79 80 81 82 82
99th 127 127 128 130 131 132 133 86 86 87 88 88 89 90
BP Levels for Boys by Age an 2eig't Percentile
SBP (mmHg) DBP (mmHg)
Age BP Percentile of Height Percentile of Height
(Year) Percentile 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
12 50th 101 102 104 106 108 109 110 59 60 61 62 63 63 64
90th 115 116 118 120 121 123 123 74 75 75 76 77 78 79
95th 119 120 122 123 125 127 127 78 79 80 81 82 82 83
99th 126 127 129 131 133 134 135 86 87 88 89 90 90 91
BP Levels for <irls by Age an 2eig't Percentile
Special populations:
.) Pregnancy
2ypertension uring pregnancy is categoriJe as:
5) Preeclampsia' de%ined as a ele.ated /P greater than or eC"al to
140590 mm Hg that appears a%ter 20 ?ee7s gestation accompanied
*y ne?)onset protein"ria (+00 mg524 ho"rs)' can lead to li%e)
threatening complications %or *oth mother and %et"s.
6) $clampsia' the onset o% con."lsions in preeclampsia' is a medical
emergency.
7) <estational 'ypertension is de%ined as ne?)onset hypertension
arising a%ter midpregnancy in the a*sence o% protein"ria'
.) 1'ronic 'ypertension is ele.ated /P that is noted *e%ore the
pregnancy *egan.
+) Superimposition of preeclampsia on c'ronic 'ypertension
126
Special populations:
.) Pregnancy 9 preeclampsia
Delivery is indicated i% pending or %ran7 eclampsia is present.
Bther?ise' management consists o% restricting activity% berest%
an close monitoring)
ntihypertensi.e agents are "sed prior to ind"ction o% la*or i% &/P
is greater than 102 to 110 mm Hg ?ith a target &/P o% 92 to 102
mm Hg.
;ntravenous 'yralaJine is most commonly "sed' and intravenous
labetalol is also e%%ecti.e. ;mmeiate0release oral nifeipine has
*een "sed' *"t it is not appro.ed *y the 8ood and &r"g
dministration (8&) %or hypertension and "nto?ard %etal and
maternal e%%ects (hypotension ?ith %etal distress) ha.e *een
reported.
127
Special populations:
.) Pregnancy 9 c'ronic 'ypertension
>t is contro.ersial ?hether treating ele.ated /P in patients ?ith
chronic hypertension in pregnancy is *ene%icial. Ho?e.er' ?omen
?ith chronic hypertension prior to pregnancy are at increase ris3
of a number of complications' incl"ding#
s"perimposed preeclampsia'
preterm deli.ery'
%etal gro?th restriction or demise'
placental a*r"ption'
heart %ail"re'
ac"te 7idney %ail"re.
128
Special populations:
.) Pregnancy 9 c'ronic 'ypertension
Met'ylopa is still considered the dr"g o% choice.
&ata indicate that "teroplacental *lood %lo? and %etal hemodynamics are
sta*le ?ith methyldopa. 1oreo.er' it is .ie?ed as .ery sa%e' *ased on long)
term %ollo? "p data (0.2 years) that has not demonstrated ad.erse e%%ects on
childhood de.elopment.
B0Bloc3ers% labetalol an 11Bs are also reasona*le alternati.es.
A1$ in'ibitors an ARBs are 7no?n teratogens and are a*sol"tely
contraindicated.
Alis3iren also sho"ld not *e "sed in pregnancy.
129
130
2T# an ot'er concomitant conitions
5) Pulmonary isease an perip'eral arterial isease
&ata s"ggests that carioselective L0bloc3ers can sa%ely *e "sed in
patients ?ith asthma or chronic o*str"cti.e p"lmonary disease.
Peripheral arterial disease' noncoronary atherosclerotic .asc"lar disease'
is a coronary artery disease ris7 eC"i.alent. !he 2000 H g"idelines no?
recommend a /P goal o% less than 1+0580 mm Hg in this pop"lation.
A1$ in'ibitors may *e ideal in patients ?ith symptomatic lo?er e:tremity
peripheral arterial disease ?ho also ha.e hypertension' as they decrease
C; e.ents in these patients. 11Bs may also *e *ene%icial *eca"se o% their
.asodilatory e%%ects on the peripheral arteries.
B0Bloc3ers ha.e traditionally *een considered pro*lematic in patients
?ith peripheral arterial disease *eca"se o% possi*le decreased peripheral
*lood %lo? secondary to "nopposed stim"lation o% )receptors that
res"lts in .asoconstriction. Ho?e.er' /)*loc7ers are not contraindicated in
peripheral arterial disease and ha.e not *een sho?n to ad.ersely a%%ect
?al7ing capa*ility.
131
2T# an ot'er concomitant conitions
6) $rectile ysfunction
1ost antihypertensi.e agents are associated ?ith erectile
dys%"nction in men.
Centrally acting agents are associated ?ith higher rates o% se:"al
dys%"nction and sho"ld *e a.oided in men ?ith erectile
dys%"nction.
st"dy o% men prospecti.ely screened %or erectile dys%"nction a%ter
*eing re%erred %or n"clear stress test imaging sho?ed that erectile
ysfunction (as a stronger preictor of severe coronary 'eart
isease t'an traitional ris3 factors (age' smo7ing' hypertension'
dia*etes' and dyslipidemia).
132
2ypertensive urgency
>deally managed *y ad@"sting maintenance therapy *y adding a ne?
antihypertensi.e and5or increasing the dose o% a present
medication. !his is the pre%erred approach to these patients as it
pro.ides a more graual reuction in /P.
AeC"ires /P red"ctions ?ith oral antihypertensi.e agents to stage 1
.al"es o.er a period o% se.eral ho"rs to se.eral days. ll patients
?ith hypertensi.e "rgency sho"ld *e ree.al"ated ?ithin 0 days
(pre%era*ly a%ter 1 to + days).
c"te administration o% a short)acting oral antihypertensi.e
(captopril' clonidine or la*etalol) %ollo?ed *y care%"l o*ser.ation
%or se.eral ho"rs to ass"re a grad"al red"ction in /P is an option %or
hypertensi.e "rgency.
133
2ypertensive emergencies
2ome(or3: /'at parenteral agents can be use for t'e treatment of
'ypertensive emergencies
4o"rce# chapter 2 in Pharmacotherapy Principles Y Practice
135
Patient $ucation
ssess patientKs "nderstanding and acceptance o% the diagnosis o%
hypertension
&isc"ss patientKs concerns and clari%y mis"nderstandings
Fhen meas"ring /P' in%orm the patient o% the reading *oth .er*ally and
in ?riting
ss"re patient "nderstands their goal /P .al"e
s7 patient to rate (1910) his or her chance o% staying on treatment
>n%orm patient a*o"t recommended treatment' incl"ding li%estyle
modi%ication. Pro.ide speci%ic ?ritten in%ormation "sing standard
*roch"res ?hen a.aila*le
Elicit concerns and C"estions and pro.ide opport"nities %or patient to
state speci%ic *eha.iors to carry o"t treatment recommendations
EmphasiJe#
the need to contin"e treatment
that control does not mean c"re
ele.ated /P is "s"ally not accompanied *y symptoms
136
;niviualiJe Treatment Regimens
>ncl"de the patient in decision)ma7ing
4impli%y the regimen to once)daily dosing' ?hene.er
possi*le
>ncorporate treatment into patientKs daily li%estyle
4et realistic short)term o*@ecti.es %or speci%ic components
o% the medication and li%estyle modi%ication plan
Enco"rage disc"ssion o% diet and physical acti.ity' ad.erse
dr"g e%%ects and concerns
Enco"rage sel%)monitoring ?ith .alidated /P de.ices
1inimiJe the cost o% therapy' ?hen possi*le
&isc"ss adherence at each clinical enco"nter
Enco"rage grad"al s"stained ?eight loss
137
,ollo(0up an Monitoring
,our aspects of treatment must al(ays be consiere#
a) /P response to attain goal'
*) adherence ?ith li%estyle modi%ications and pharmacotherapy'
c) progression to hypertension)associated complications'
d) dr"g)related to:icity.
T'erefore:
Bnce antihypertensi.e dr"g therapy is initiated' most patients sho"ld ret"rn %or
follo( up an ajustment of meications at appro:imately monthly inter.als "ntil
the /P goal is reached.
1ore %reC"ently %or those ?ith 4tage >> H!- or comor*id conditions
%ter /P goal achie.ed 9 contin"e %ollo? "p e.ery +)3 months
Serum potassium an creatinine sho"ld *e monitored at least 192 times5year.
Laboratory mar3ers 9 at least semi)ann"ally
1ore o%ten i% necessary d"e to speci%ic dr"g
Cardio.asc"lar ris7 %actors sho"ld *e treated to their respecti.e goals' and to*acco
a.oidance sho"ld *e promoted .igoro"sly.
Contin"ally monitor %or sie effects or averse rug reactions
138
Monitoring Drug T'erapy
&ependent on any
presenting symptoms
8atig"e' =ethargy
Con%"sion
T&epressedU
4hortness o% *reath
/P and HA
=a*oratory data
/P' HA and AA
&epression 4cale
"sc"ltation5P8!
Therapeutic
Toxic
Subjective
Objective
Example: Beta blocker
1ase stuy
,!' a 22)year)old %rican)merican ?oman' comes to yo"r clinic
?ith a recent diagnosis o% hypertension.
4he is 2<2U (132 cm) tall and ?eighs 130 po"nds (02.0 7g) ?ith a
*ody mass inde: (/1>) o% 23.3 7g5m2.
,! does not "se to*acco or drin7 alcohol' and e:ercises a*o"t once
a ?ee7.
Physical e:am ?as "nremar7a*le' *"t an electrocardiogram
re.ealed le%t .entric"lar hypertrophy.
/aseline la*oratory tests ?ere signi%icant %or %asting *lood gl"cose
o% 124 mg5d= (3.88 mmol5=)' ser"m creatinine o% 1.2 mg5d= (1++
mmol5=)' total cholesterol o% 200 mg5d= (2.18 mmol5=)' high)
density lipoprotein cholesterol o% 40 mg5d= (1.04 mmol5=)'
triglycerides o% 200 mg5d= (2.23 mmol5=)' and lo?)density
lipoprotein cholesterol o% 120 mg5d= (+.11 mmol5=). $rinalysis ?as
positi.e %or microal*"min"ria.
/lood press"re today ?as 132583 mm Hg.
1ase stuy !Muestions"
Fhat signs o% target organ damage does ,! e:hi*itP
>s more e:tensi.e testing %or identi%ia*le ca"ses o% hypertension
indicated at this timeP
/ased on the in%ormation presented' create a care plan %or ,!<s
hypertension. !his sho"ld incl"de#
(1) goals o% therapy'
(2) a patient)speci%ic therape"tic plan'
(+) a plan %or appropriate monitoring to achie.e goals and a.oid
ad.erse e%%ects.
Fhat antihypertensi.e agents are less e%%icacio"s in %rican
mericansP
Sources:
pplied !herape"tics
Pharmacotherapy Principles Y Practice