Upload
triponia-steffy-oktia
View
217
Download
0
Embed Size (px)
Citation preview
ESSENTIAL HYPERTENSION , COMBINATION OF CCB AND ARB,
CHOICE AGENTS
BYDr. BAMBANG SN, Sp. PD
DEPARTMENT OF INTERNAL MEDICINEGENERAL HOSPITAL OF Dr. SOEDARSO
PONTIANAK
Presented on Round Table Discussion of Hypertension
April, 07th 2013, Pontianak, West Kalimantan
I. INTRODUCTIONHypertension is still an important problem in the world time by time, because of highly prevalence and its serious complication esspecially cardio vascular disease (CVD).
More than 95% cases is essential hypertension, the rest is secondary.Associated with modern style, the risk factors such as sedantary life, physical inactivity, hyperlipidemie, obesity, distress, and tobacco smoking have important role on pathogenesis essential hypertension.
Life style modification is a basic way in management of hypertension before or together medication treatment.
Provider must recognize profile of anti-hypertensive agent that will be given to hypertensive patient for safety and better result.
Blood pressure can be controlled by medication besides life style modification to avoid or delay acute or chronic complication esspecially CVD.
II. PATHOGENESIS II. PATHOGENESIS There are many factors contribute to controle blood There are many factors contribute to controle blood
pressure, such as genetic, obesity, stress, sodium pressure, such as genetic, obesity, stress, sodium intake, nephron number and endothelium derived intake, nephron number and endothelium derived factors.factors.
Renin angiotensin aldosteron system is the most Renin angiotensin aldosteron system is the most important system, that regulate blood important system, that regulate blood pressurepressure
When thWhen thisis system does uncontrole, blood pressure will system does uncontrole, blood pressure will go up persistanly and hypertension will accure. go up persistanly and hypertension will accure.
To control and lower blood pressure, we have to stop To control and lower blood pressure, we have to stop production of angiotensinproduction of angiotensin II II or eliminate its effect on or eliminate its effect on the receptor.the receptor.
All conditions as risk factors of All conditions as risk factors of hypertension produce oxidatif stress, that hypertension produce oxidatif stress, that affect endothelial dysfuction and smooth affect endothelial dysfuction and smooth muscle activation.muscle activation.
Treatment of hypertension must be started Treatment of hypertension must be started by lifestyle modification and then followed by lifestyle modification and then followed drug medication.drug medication.
Lifestyle modification incluLifestyle modification includede weight weight reduction, eating plan, sodium reduction reduction, eating plan, sodium reduction intake, phisycal activity and moderation intake, phisycal activity and moderation alcohol consumption and so on.alcohol consumption and so on.
Some of Factors Involved in Controlling Blood Pressure
Excess Reduced Stress Genetic Obesity Excess Reduced Stress Genetic Obesity EndotheliumEndothelium sodium nephron alteration derivedsodium nephron alteration derived intake number factors intake number factors
Renal Decreased Sympathetic Renin Cell Hyper-Renal Decreased Sympathetic Renin Cell Hyper- sodium filtration nervous over angiotensin membrane insulinemiasodium filtration nervous over angiotensin membrane insulinemia retention surface activity excess alteration retention surface activity excess alteration
Fluid VasoFluid Vaso volume constrictionvolume constriction
Preload Contractability Functional Preload Contractability Functional StructuralStructural constriction constriction hypertrophyhypertrophy
BLOOD PRESSURE = CARDIAC OUTPUT X PERIPHERAL RESISTANCEBLOOD PRESSURE = CARDIAC OUTPUT X PERIPHERAL RESISTANCE Hypertension = Increased CO and/or Increased PRHypertension = Increased CO and/or Increased PR
AutoregulationAutoregulation
The Renin-Angiotensin-Aldosteron System.
Adrenal Kidney Intestine CNS Peripheral nervous Vaskular Heart cortex system smooth muscle Adrenergic facilitation Aldosteron Contractility Symphatetic discharge Distal Nephron Sodium and Thirst Vasopressin VasoconstrictionReabsorption water reabsortion salt appetite release
Maintain or increase Total peripheral Cardiac ECFV resistance output
ANGIOTENSINOGEN Renin ANGIOTENSIN I Converting enzyme ANGIOTENSIN II
Angiotensinase A
Macula densa signalRenal arteriolar pressureRenal nerve activity
ANGIOTENSIN III
Angiotensinogen
Angiotensin I
Angiotensin II
AT1 Receptor AT2 Receptor
VasoconstrictionSalt/water retentionRemodelling
AntiproliferativeCell differentiationTissue repair
VasodilationNatriu-/diuresisAnti-remodelling
NO
BK IIReceptor
ChymaseTrypsinPeptidase
Renin
ACE-Kininase II
Bradykinin
InactiveDegradationproducts
ACE-I
ARB
The Role of ACE Inhibitor and ARB in Decreasing Blood Pressure
Renin-Angiotensin Aldosterone System
Angiotensinogen
Non-ACE pathways(eg, chymase)
Vasoconstriction Cell growth Na/H2O retention Sympathetic activation
Renin Angiotensin I
Angiotensin IIACE
Cough,angioedema
Benefits? Bradykinin Inactive
fragments
Vasodilation Antiproliferation
(kinins)
Aldosterone AT2
AT1
III. Classification of Hypertension
• The classification of hypertension is changed time by time according to the improvement and development knowledge and experiences.
• To be called hypertension, if blood pressure the same or more 140/90 mmHg.
Blood Pressure Classification (JNC 7)
Normal <120 and <80
Prehypertension 120–139 or 80–89Stage 1 Hypertension 140–159 or 90–99Stage 2 Hypertension >160 or >100
BP Classification SBP mmHg DBP mmHg
Blood Pressure Classification (ESH)
CategoryCategory SSyystolistolicc (mmHg)(mmHg)
DDiiastoliastolicc (mmHg) (mmHg)
OptimalOptimal <120<120 anandd <80<80Normal Normal 120–129120–129 anandd 80–8480–84High High NormaNormall 130–139130–139 and/and/
oror85–8985–89
HHyypertenpertentiontionGradeGrade 1 ( 1 (mild)mild) 140–159140–159 and/and/
oror90–9990–99
GradeGrade 2 ( 2 (moderatemoderate)) 160–179160–179 and/and/oror
100–109100–109
GradeGrade 3 ( 3 (severesevere)) 180180 and/and/oror
110110Guidelines Committee. J Hypertens 2003;21:101153
Table 2. Awareness hypertension people
• How serious and dangerous of hypertension because it has many complications, acute and chronic esspecially cardiovascular events.
• It is our task and responsibility to socialize and inform about hypertension and its implication to all people, esspecially those at risk.
• Unfortunetelly not all people know about their blood pressure, also hypertension patients do not understand well and not allert to seek medical acces.
IV. Prevalence of Hypertension
• In fact, prevalence of hypertension is increased time by time.
• It is influenced by several condition and risk factors. The older people the higher blood pressure.
Franklin, S.S., J Hypertens 1999; 17 (suppl 5): S29-S36
Hypertension is one of the most frequent clinical discorders.
0
10
20
30
40
50
60
70
18-29 30-39 40-49 50-59 60-69 70-79 80+
SBP > 140 mm Hg DBP > 90 mm Hg
age (yrs)
prev
alen
ce o
f hyp
erte
nsio
n (%
)
4 11
21
44
54
64 65
Prevalence of Hypertension
V. Complication of hypertension
• Clinical trials proved, the high corellation between hypertension and prevalence of stroke.
• People with hypertension have high risk to have chronic renal diseases. The higher blood pressure the hinger the risk decreasing of renal function.
• Systolic blood pressure interact with diabetes mellitus to increase risk of cardiovascular disease.
BP directly correlates with risk of stroke
Adapted from He and Whelton, J Hypertens, 1999.
<112 112- 118- 121- 125- 129- 132- 137- 142- ≥151<71 71- 76- 79- 81- 84- 86- 89- 92- ≥98
Rel
ativ
e ris
k of
str
oke
mm Hg
0
1
2
3
45
6
7
8
9
Systolic BPDBP
Systolic BP
Diastolic BP
MRFIT
Hypertension Linked To Chronic Renal Disease Among 332,544 Men Screened for MRFIT
0
50
100
150
200
250
<8080-84
85-8990-99
100-109110
180 160-179 140-159 130-139 120-129 <120
Systolic BP (mm Hg) Diastolic BP (mm Hg)
Adapted from Klag MJ, et al. N Engl J Med. 1996;334(1):13-18.© Massachusetts Medical Society
250
200
150
100
50
0Age
-Adj
u st e
d R
ate
o f E
S RD
Per
1 00 .
0 00
P er s
o n-Y
e ar s
Elevated systolic BP interacts with diabetes to increase CVD risk
MRFIT: men with diabetes and elevated systolic BP are at greater risk of CVD than those without
diabetes
0
50
100
150
200
250
300
<120 120-139 140-159 160-179 180-199 ≥200
CVD
dea
ths
per 1
0,00
0 pe
rson
-ye
ars
Systolic BP (mm Hg)
Patients with diabetesPatients without diabetes
Stamler et al, Diabetes Care, 1993.
VI. Treatment of Hypertension• Trials and experiences indicate that decreasing blood
pressure decreasing prevalence all complication.• Every lowering systolic blood pressure of 23 mmHg, lower
incidens of stroke, heart failure and myocardial infartion.• Doctors have to initiate treatment as soon as possible for
patients with hypertension, to ovoid and eliminate acute or chronic complication.
• There are 2 ways approachs, the 1st is nonfarmacologic and the 2nd is farmacologic. Don’t wait to treat hypertension, more earlier more better result.
In every 23 mmHg reduction in Systolic Blood In every 23 mmHg reduction in Systolic Blood Pressure, Pressure, lowers incidence of........lowers incidence of........
-42%
-26%-29% -30% -31%
-45%
-30%
-15%
0%
Per
cent
Red
uctio
n
*Fatal and nonfatal heart failure and nonfatal myocardial infarction and sudden death **Fatal and nonfatal heart failure and nonfatal myocardial infarction, sudden death and stroke
* **Stroke All cardiac
end pointsMIHeart
Failure
All fatal/ nonfatal cardiovascular
end points
Algorithm for Treatment of Hypertension
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling Indications
Lifestyle Modifications
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension(SBP 140–159 or DBP 90–99
mmHg) Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling Indications
Not at Goal Blood Pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
http://www.nice.org.uk/download.aspx?o=CG034fullguideline.Accessed June 2006
UK NICE Guidelines: Treatment for Recent Diagnosis of Hypertention
*If ACE inhibitor (ACEI) not tolerated
ACEI (or ARB*) + CCB orACEI (or ARB*) + thiazide diuretic
<55 years
ACEI (or ARB*) + CCB + diuretic
CCB or thiazide-type diureticACEI (or ARB*)
55 years or black at any age
Add further diuretic therapy, α-blocker, or β-blocker.
Consider seeking specialist advice
Step 1
Step 2
Step 3
Step 4
Lifestyle ModificationJNC VII
Drugs RecomendationJNC VII/ WHO
• Diuretic• Beta blocker• ACE inhibitor• Calcium channel blocker• Angiotensin receptor blocker
Diuretic
AT1 receptorblocker
Calcium antagonist
ACE inhibitor
Alpha blocker
Beta blocker
European Society Of Hypertension
2003
Possible combination of different classes of anti hypertension drugs
Most rationalcombination
Proven bene-ficial in trialsJournal. Of Hypertension 2003
Current Guidelines Recommend Initiating Combination Therapy Early in Patients with Stage 2 Hypertension or High Cardiovascular Risk
• JNC 7 guidelines state1:“When BP is more than 20 mmHg above systolic goal or 10 mmHg above diastolic goal, consideration should be given to initiate therapy with 2 drugs...”
• ESH/ESC guidelines state2:“A combination of two drugs at low doses should be preferred as first step treatment when initial BP is in the grade 2 or 3 range or total cardiovascular risk is high or very high.”
1Chobanian et al. Hypertension 2003;42:1206–52 2Mancia et al. J Hypertens 2007:25:110587
ESH = European Society of HypertensionESC = European Society of CardiologyJNC = Joint National Committee
Angiotensin II Effects
– Vasoconstriction– Aldosteron secretion– Sodium reabsorption– Symphatic activation– Vasopressin release– Hypertrophy and proliferation of
myocardium and vascular cells
ARB
AT Receptors:•Heart•Vascular•Lung•Liver•Kidneys•Adrenal, Prostate•Placenta, Brain
Angiotensin Receptor Blocker
• Angiotensin Receptor– Mostly on heart and vascular– Another organs : lungs, liver, kidneys,
adrenal gland, postate gland, brain, placenta
– AT1 & AT2
– AT1 effects dominantly on cardiovascular organ
counter-regulation synergi
Synergisticlowering BP
Increased cllinical effects
Amlodipin Arteriodilation Peripheral Edema Effective in low renin level Decreased myocardial ischemia
Amlodipin Stimulates RAS Minimal effect on
CHF and kidneys
Rational Concept of CCB-ARB
Valsartan Venodilation Decreased peripheral edema Effective in high renin level No effect on cardiac ischemia
Valsartan Inhibits RAS Usefull on CHF and
kidneys BP
ARB minimizes CCB side effect– peripheral edema
CCB mendilatasi arteri
Diameter vena tidak berubah
ARB mendilatasi arteri dan vena
Single mechanism of CCB
Combination mechanism of CCB+ARB
Opie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:4273White et al. Clin Pharmacol Ther 1986;39:4348
Gustaffson. J Cardiovasc Pharmacol 1987;10(Suppl 1):S12131
Illustration modified from www.lotrel.com
Artery Dilation
(CCB andARB)
Vein Dilation(ARB)
Capillary bed
Opie. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:4273White et al. Clin Pharmacol Ther 1986;39:438; Gustaffson. J Cardiovasc Pharmacol
1987;10(Suppl. 1):S12131; Messerli et al. Am J Cardiol 2000;86:11827