Download - JNC8 & Chlorthalidone
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Whats New In
Hypertension
JNC VIII & Chlorthalid
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JNC VIII
An executive summary of the ev
and desined to provide recommendations
For
All Clinicians
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!anel "ist
#ore than $%%nominees from vexpertise inCardioloyHypertension'ndocrinoloy!harmacoloyNephroloy
Clinical (rials etc)
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*oal +!
,nderlined !oints di-erent from
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0ru !rescri1ed
Population Drug Prescrib
Non Black Thiazide-type diuretic,Calcium channel blocker Angiotensin-con"erting einhibitorAC#$!, orAngiotensin receptor bloc
Black Thiazide-type diuretic,Calcium channel blocker CC
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Population Drug Prescrib
&ithDiabetes'ellitus
Thiazide-type diuretic,Calcium channel blocker Angiotensin-con"erting einhibitorAC#$!, orAngiotensin receptor bloc
&ith C(D AC#$ or A%B to impro"e kidnoutcomes)
0ru !rescri1ed
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2%3$ Hypertension *uide#anaement Alorithm
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Adults aed 4 35
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*eneral !opulation
2
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2
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0ia1etes or C60 !atients
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7trateies to 0oseAntihypertensive 0ru
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A 7tart one dru titrate tmaximum dose and then second dru
+ 7tart one dru and the
Antihypertensive 0ru
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C
+ein with 2 drus at the stime
either as 2 separate pills oa sinlepill com1ination
Antihypertensive 0ru
+lood !ressure 4 38%93
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:ole of Chlorthalidon
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(hia;ide vs (hia;ide.li"ac!hysioloical action is sclinical bene*ts are mo
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'volution of Chlorthalidone
+se o doses o .. to /.. mg dail
Dose o 01, 1. or 1 mg daily - BPreduction
2)1 mg and 1 mg daily, o3erbest e4cacy-to5side e3ect rat
6andmark Trial7 '%F$T,89#P
6andmark Trial7 A669AT
Feasibility o /)1 mgdose
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0ual #ode of action
%eduction in pe"ascular resistan
%eduction inplasma "olume
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"on term action
P:% reduction 7 theories
Interference with intracellular Ca2+ releaby nor- adrenaline
Inhibition of Rhokinase activity
Reduction in arterial edema
Reduction in vascular reactivity
:ao 77 et al Ind) J) !harmac) 3?@$ ?$B.?3 Dhu D et al Hypertension) 2%% Ee1F$@2G2??.Btext1oo< of cardiovascular medicine th 'd) 3BB/ #usso #N +ra; J #ed +
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"on half life of chlorthalidone
o Chlorthalidone has the longest elimination o /. hrs)
o The diuretic e3ect sets in ater to ; hours
reaches its ma-0 hr)
Carter B6 e
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CTD- $nternationale
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(he 7ystolic Hypertension inthe 'lderly !roram @7H'!
89#P %esearch ro
Cohort 4,736; 43% men
Age
60 yrs old; mean 71.6 yrs old
Eligibility Systolic ! 160"1# mm$g and iastolic ! m
esign o'ble blind; (lacebo control
)hera(y Chlorthalidone *atenolol as ste( "+
'ration 4. years
! change Systolic ! 1" mm$g
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ChangeinBP
(
mmHg)
Years
7H'!Chane in +lood !ressure
Placebo(n=2,371)
Active ! (n=2,3"#)
Years$ 1 2 3 % # $ 1 2 3
&'stolic BP&'stolic BP iastoliastol
Pla(n=
A(n
7H'! :esults
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7H'!G :esults
C96%T9A6$DN# :8) P6AC#B
89#P Cooperati"e %esearch roup)JAMA) 2@@2?/17;115;/=)
%% @C$!.)/= .
.)0; .
.)=/ .
.)/> .
.)>0 .
8troke
C9D
C9F
C:D
Death.) 2)/2)..)= .)/ .)> 2) 2)=
Fa"ors chlorthalidone Fa"ors placebo
7 l d f l 7
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C
umulati"e8t
roke
%ate
Per2..Pers
ons
'onths o FolloE-up
7H'!G Eatal and Non.fatal 7tro
# t lit : d ti
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#ortality :eduction
'%F$T
@ centres 9CTK and / centres chlorthalidone
9CTK group had a == higher mortality)
Patients Eere shited to chlorthalidone
6ater Eith chlorthalidone the trend Eas re"ersthe same group had a > loEer risk)
Circulation) 2
#:EI(G Impact on Lutcomes Af
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ierence eteen S 8ers's 9C
p7witchin Erom HC(D to Chlortha
'ultiple %isk Factor $nter"
%esearch roup)
'%F$T 'ultiple %isk Factor
$nter"ention Trial? 8$special
#ultiple :is< Eactor Intervention
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#ultiple :is< Eactor InterventionChanges From Baseline at 48 Mont
#rnst '#, et al) #y"ertension) .22
"or $nteractio
"or $nteraction )..2
"or $nteraction H )..2
#ultiple :is< Eactor Intervention
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pComparison of Diuretic Therap
Ad
Dorsch 'P, et al) #y"ertensio
Chlorthalido
ne9CTKDrug8topped
Chlorthalidone "s DrugH )...29CTK "s Drug 8toppedChlorthalidone "s 9CTK
AdJusted estimates Eere controlledor by age, race, smoking status,'%F$T randomized group, diuretic
dose, 8BP, 6D6, 9D6, and baseline
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Chlorthalidone 7afety
>#lectrolyteimbalance
>9ypokalemia>6ipid pro*le>9yperglycemi
Indian 'xperiencewith low dos
http://www.google.co.in/imgres?imgurl=http://www.hypertension-bloodpressure-center.com/images/malignant_hypertension.jpg&imgrefurl=http://www.hypertension-bloodpressure-center.com/hypertension-symptoms.html&usg=__rquxM6c41KRCGPcw9GOqbB_k64U=&h=283&w=300&sz=57&hl=en&start=18&zoom=1&tbnid=IYGIzLJvFLAOkM:&tbnh=109&tbnw=116&prev=/images?q=hypertension&hl=en&sa=G&gbv=2&tbs=isch:1&itbs=1 -
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chlorthalidone @C(0
5at're o st'dy 'ration 5o. o (atr
1 6." mg Chlorthalidone
6." mg Chlorthalidone : atenolol
"4 ees 3
" 6." mg Chlorthalidone :2eto(rolol
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7+! reduction with monotherap
p valu
0+! reduction with monotherap
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0+! reduction with monotherap
p valu
'l t l t h
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'lectrolyte chane
St'dy =ro'(s 8isit Sodi'm !otassi'm
Chlorthalidoneaseline 13.37 4."1
End 13."# 3.#7
Pareek et al, Current 'edical %esearch and pinions
A""HA( report on hypo
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A""HA( report on hypo
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p p
Trials lasting less than a year ha"e shoEn s
change in lipid le"els, 6ong term studies hato shoE ad"erse e3ect on lipid concentratio
8maller doses noE in use do not alter lipid p
'-ect on 1lood suar in India
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'-ect on 1lood suar in Indiatrial
St'dy =ro'(s 8isit >S
Chlorthalidoneaseline 101.4# 137.13
End 10.7 13."4
Pareek et al, Current 'edical %esearch and pini
Hyperlycemia with
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yp ychlorthalidone
A669AT
There Eas no e3ect o change in F le"el onand renal outcomes)
89#P
NeE cases o diabetes >)/ "s 0)1 in place No signi*cant increase in C:D mortality com
urEitz et al Ann $nt 'ed 22>7 0;, 2@@, Paul ( E
C(0 vs HC(D
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C(0 vs HC(D
&hich EayL
Potency
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Potency
Chlorthalidone is 2)1 to ). times as potent ahydrochlorothiazide)
Carter +" et
9CTK 1.mg 1mg2)1mg
Chlorthalidone 1mg 2)1m/)1 mg
7uperior to HC(D
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A randomized, single blinded clinical trial sthat, ater > Eeeks patients Eho Eere takmgMday chlorthalidone e
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+etterniht time control of +
5ighttime mea*mm o $g
Chlorthalidone " mg?day -13.
$ydrochlorothiaide 0 mg?day -6.4
The higher potency o chlorthalidone resulted in duration o action that pro"ided night time bloodcontrol and hence Eas e3ecti"e in pro"iding addiprotection rom stroke and myocardial inarction
+arry "C Hy
Pleiotropic bene*ts o
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Chlorthalidone
%educes platelet aggregationess potential o clot ormation
Better blood oE
Promotes angBetter blood$ess load o
%educes "ascular permeabilityBetter blood supply
$ess load on heart
etter circ'latory (erormance
ess load on heart
%yan &oodman
Chlorthalidone O)) Cl
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Apart
'illions o hypertensi"e patients ha"e bea less e3ecti"e drug 9CTK! that almostdid not protect them as Eell as CTD Eou
Norman Kaplan Hypertension Octobe
Clinical expert opinio
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Clinical expert opinio
0r Henry +lac