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HIPERTENSI

Dr, Suhaemi, SpPD,Finasim


DEFINISI
 Tekanan Darah (TD): refleksi kardiovaskular

 TD sistolik : dipengaruhi oleh curah jantung (CO),


dapat berubah dalam waktu singkat (aktifitas fisik ringan,
emosi)

 TD diastolik : refleksi dari resistensi perifer, bila vasokonstriksi


arteriol → TD diastolik ↑
sukar dipengaruhi faktor emosi dan aktifitas fisik ringan

 HIPERTENSI : kondisi abnormal hemodinamik (fungsi


pengaturan/kontrol)
→ batasan hipertensi dipakai kriteria TD sistolik
dan/atau TD diastolik
If we do not treat the hypertension

http://www.lifespan.org/adam/graphics/images/en/18166.jpg
Consequences of Hypertension
Consequences of Hypertension

http://www.massgeneral.org/vascularcenter/body/stroke.jpg
Hypertensive nephropathy

http://www.ndt-educational.org/images/Marcantonifig1.jpg
Fundoscopy/ Vascular
DEFINISI

• Tekanan nadi (pulse pressure) = TD sistolik – TD


diastolik

• Tekanan arteri rata-rata (mean arterial


pressure/MAP) = (TD sistolik + 2xTD diastolik)
3
BP = CO x SVR

SV x HR
 BP : blood pressure
 SVR: systemic vascular-resistance
 SV : stroke volume
 HR : heart rate
Blood Pressure
Determining Factors
Cardiac Output:
Peripheral
Stroke Volume Resistance **
Heart Rate
Vasodilators
Force of Contraction
ACE Inhibitors
Beta Blockers
Calcium Channel
BP
Blockers

Blood Volume **

Diuretics ACE Inhibitors


DEFINISI

• HIPERTENSI PRIMER (90 – 95%)


hipertensi yang tidak diketahui penyebabnya

• HIPERTENSI SEKUNDER (5 – 10%)


hipertensi yang diketahui penyebabnya
Patogenesis Hipertensi

MULTIFAKTORIAL
PATOGENESIS
Hipertensi primer : Penyakit multifaktorial

• Interaksi faktor-faktor risiko seperti : diet / asupan


garam, stres, ras, obesitas, merokok, genetis
• Sistim saraf simpatis : tonus simpatis dan variasi diurnal
• Keseimbangan antara modulator vasodilatasi dan
vasokonstriksi pembuluh darah : endotel, remodeling
endotel, otot polos dan interstitium
• Pengaruh sistim otokrin setempat  sistem RAA
Renin - Angiotensin
Glomerulus and Bowman’s Capsule

Juxtaglomerular
Cells

Decreased BP
Renin Release

Formation of
Angiotensin

Increased Vasoconstriction
Increased Aldosterone
with Increased Na++ and
Fluid Retention
FAKTOR2 YANG BERPENGARUH PADA PENGENDALIAN TD
asupan Na jumlah stress perubahan obesitas faktor2 yg
berlebih nefron genetis berasal dari
Endotel

retensi permukaan Aktifitas Renin perubahan hiper-


Na ginjal filtrasi Berlebih Angiotensin membran sel insulinemia
Saraf simpatiis release

­volume konstriksi vena


cairan

konstriksi hipertrofi
Preload  kontraktilitas fungsional struktural

TEKANAN DARAH CURAH JANTUNG TAHANAN PERIFER


Hipertensi
= Peningkatan CJ
X Peningkatan TP
dan/atau
=
autoregulation
Kaplan
Hipertensi Sekunder
Sleep apnea
Drug-induced or related causes
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Chronic steroid therapy and Cushing’s syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease

JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314


• According to the National Institutes of Health
(NIH), if hypertension (HTN) is left untreated
– 1/2 of hypertensive clients will die of heart disease
– 1/3 of hypertensive clients will die of a stroke
– Rest of clients will die of renal failure
Blood Pressure Classification JNC VII
BP SBP DBP
Classification mmHg mmHg
Normal <120 and <80
Prehypertension 120–139 or 80–89
Stage 1 140–159 or 90–99
Hypertension
Stage 2 >160 or >100
Hypertension
Mengapa Tekanan Darah
Harus Diturunkan ?
FRAMINGHAM STUDY
HIPERTENSI :
The Disease Continuum
Early Paradigm
Natural History of CVD Progression
Elevated BP Target Organ Damage
More Recent Paradigm

Vascular Dysfunction Elevated BP Target Organ Damage

A Proposed Future Paradigm

Endothelial Vascular Elevated BP Target Organ


Dysfunction Damage
? Dysfunction LVH
Angina
Pectoris
Renal MI Stroke
Damage
Hypertension Syndrome
It’s More Than Just Blood Pressure

Decreased
Arterial
Obesity Compliance Endothelial
Dysfunction

Abnormal Lipid Abnormal Glucose


Metabolism Metabolism

Accelerated HYPERTENSION Neurohormonal


Atherogenesis Dysfunction

LV Hypertrophy Renal-Function
and Dysfunction Changes
Blood-Clotting
Abnormal Insulin
Mechanism
Metabolism
Changes

Kannel WB. JAMA. 1996;275:1571-1576. Weber MA et al. J Hum Hypertens. 1991;5:417-423. Dzau VJ et al. J
Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5.
Routine steps for accurate measurement
of blood pressure

• Rest the patient (seated) for at least 5 mins in a quiet


confortable room
. Use a calibrated sphygmomanometer (a validated and recently
calibrated electronic device may may also be used)
. Choose cuff with appropriate width of bladder
. Record with cuff at heart level
. Deflate cuff at 2 mmHg/sec
. First sound = systolic reading, disappearance = diastolic
reading
. Repeat measurement at least x2 (first visit: x3) & take average
value
. Take BP in both arms at least once; record which arm is used;
patient position ( seated, supine, standing) & pulse rate.
. Measure BP at + 1 & 5 mins after standing ( especially in older
patients and those with diabetes).
BP Measurement Techniques
Method Brief Description
In-office Two readings, 5 minutes apart, sitting
in chair. Confirm elevated reading in
contralateral arm.
Ambulatory BP Indicated for evaluation of “white-coat”
monitoring HTN. Absence of 10–20% BP decrease
during sleep may indicate increased
CVD risk.
Self-measurement Provides information on response to
therapy. May help improve adherence
to therapy and evaluate “white-coat”
HTN.

JNC 7 2003
How to measure blood pressure accurately

 ……… sphygmomanometer
 Patient should be seated and relaxed, preferably for several
minutes
prior to to the measurement and in a quiet room.
 Appropriate cuff size.
 Average the readings. If the first two readings differ by more than 10 mmHg
systolic or 6 mmHg diastolic or if the initial readings are high, take several
readings after five minutes of quiet rest, until consecutive readings do not
vary by greater than these amounts.
 Ideally, patients should not take caffeine-containing beverages or
smoke for at least two hours before blood pressure is measured,
………………….. Australia, 2004
CV Mortality Risk Doubles with
Each 20/10 mm Hg BP Increment*
8
7
6

CV 5
mortality 4
risk
3
2
1
0
115/75 135/85 155/95 175/105
SBP/DBP (mm Hg)

*Individuals aged 40-70 years, starting at BP 115/75 mm Hg.


CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure
Lewington S, et al. Lancet. 2002; 60:1903-1913.
JNC 7. JAMA. 2003;289:2560-2572.
Preparation for measurement
• Patient should
abstain from eating,
drinking, smoking
and taking drugs that
affect the blood
pressure one hour
before
measurement.
Preparation for measurement

• Because a full
bladder affects the
blood pressure it
should have been
emptied.
Preparation for measurement

• BP take in quiet
room and
comfortable
temperature, must
record room
temperature and
time of day.
BLOOD PRESSURE: MEASUREMENT
Ascultatory method of
blood pressure measurement Nokolai Korotkoff, 1905
Blood Pressure Assessment:
Patient preparation and posture
Standardized Preparation:

Patient
√ 1. No acute anxiety, stress or pain.
2. No caffeine, smoking or nicotine in the
preceding 30 minutes.
3. No use of substances containing adrenergic
stimulants such as phenylephrine or
pseudoephedrine (may be present in nasal
decongestants or ophthalmic drops).
√ 4. Bladder and bowel comfortable.
5. No tight clothing on arm or forearm.
6. Quiet room with comfortable temperature
7. Rest for at least 5 minutes before measurement
√ 8. Patient should stay silent prior and during the
procedure.
Measuring Blood Pressure

Slide 9-36
Complications of Hypertension:

Hypertension
is a risk factor
TIA, stroke LVH, CHD,
HF
Retinopathy Renal
Peripheral vascular failure
disease
TIA = transient ischemic attack; LVH = left ventricular hypertrophy; CHD = coronary heart disease
HF = heart failure.
Cushman WC. J Clin Hypertens. 2003;5(Suppl):14-22.
Benefits of Lowering BP

Average Percent Reduction


Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure50%
Framingham Heart Study (1983)

CV Risk Profile
703
700
8 Year Probability Per 1,000

600
500 459
400
326
300
210
200
100 46

Systolic BP: 105 >>> 185 105 >>> 185 105 >>> 185 105 >>> 185 105 >>> 185
Cholesterol: 185 335 335 335 335
Glucose Intol.:0 0 + + +
Cigaretes: 0 0 0 + +
ECG-LVH: 0 0 0 0 +

Kannel, 1983
CXR:
Cardiomegaly
pleural effusions
interstitial edema
Pulmonary venous redistribution
Echocardiography

“Confirm” diagnosis with transthoracic echocardiography


– LV dimensions and ejection fraction
– Systolic versus diastolic function
– Valvular disease
– Pulmonary hypertension

All patients, Class 1C


Bagan 3. Sisi kerja obat anti HT
Bagan 4. Sistem RAA
National Heart, Lung, and Blood
Institute
National High Blood Pressure
U.S. Department of
Education Program
The Seventh Report of the
Health and Human
Services

Joint National Committee on


National Institutes
Prevention, Detection,
of Health
Evaluation, and Treatment of
High Blood Pressure (JNC 7)
National Heart, Lung,
and Blood Institute
Lifestyle Interventions for Prevention or Treatment
of Hypertension

Intervention Blood Pressure Effect


Exercise 5-10 mm Hg (>30 min >3x/wk)
Weight reduction 1-2 mm Hg/Kg

Alcohol intake reduction 1 mm Hg/drink/d

Sodium intake reduction 1-3 mm Hg/40 mmol/d

DASH diet 3-10 mm Hg 

Adapted from Cushman et al. Endocrine Practice 1997;3:106 & Sacks, et al. NEJM 2001;334:3
JNC 7 Algorithm for Treatment of Hypertension

Lifestyle
Lifestyle Modifications
Modifications

Not
Not at
at Goal
Goal Blood
Blood Pressure
Pressure (<140/90
(<140/90 mm
mm Hg)
Hg)
(<130/80
(<130/80 mm Hg for those with diabetes or chronic
mm Hg for those with diabetes or chronic kidney
kidney disease)
disease)

Initial
Initial Drug
Drug Choices
Choices

Without
Without Compelling
Compelling With
With Compelling
Compelling
Indications
Indications Indications
Indications

Stage
Stage 11 Hypertension
Hypertension Stage
Stage 22 Hypertension
Hypertension Drug(s)
Drug(s) for
for the
the compelling
compelling
(SBP
(SBP 140-159
140-159 or
or DBP
DBP 90-99
90-99 mm
mm Hg)
Hg) (SBP
(SBP >160
>160 or
or DBP
DBP >100
>100 mmmm Hg)
Hg) indications
indications
Thiazide-type diuretics for most
Thiazide-type diuretics for most 2-drug combination for most (usually
2-drug combination for most (usually Other
Other antihypertensive
antihypertensive drugs
drugs
May
May consider
consider ACEI,
ACEI, ARB,
ARB, BB,
BB, CCB,
CCB, thiazide-type
thiazide-type diuretic
diuretic and
and (diuretics,
(diuretics, ACEI, ARB, BB, CCB)
ACEI, ARB, BB, CCB)
or
or combination
combination ACEI,
ACEI, or
or ARB,
ARB, or
or BB,
BB, or
or CCB)
CCB) as
as needed
needed

Not
Not at
at Goal
Goal
Blood Pressure
Blood Pressure

Optimize
Optimize dosages
dosages or
or add
add additional
additional drugs
drugs
until
until goal
goal blood
blood pressure
pressure is
is achieved
achieved
Consider
Consider consultation
consultation with
with hypertension
hypertension specialist
specialist

Chobanian et al. JAMA. 2003;289:2560-2572.


Target Organ Damage
 Heart
• Left ventricular hypertrophy
• Angina or prior myocardial infarction
• Prior coronary revascularization
• Heart failure
 Brain
• Stroke or transient ischemic attack
 Chronic kidney disease
 Peripheral arterial disease
 Retinopathy
Laboratory Tests
 Routine Tests
• Electrocardiogram
• Urinalysis
• Blood glucose, and hematocrit
• Serum potassium, creatinine, or the corresponding estimated GFR, and calcium
• Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density
lipoprotein cholesterol, and triglycerides
 Optional tests
• Measurement of urinary albumin excretion or albumin/creatinine ratio
 More extensive testing for identifiable causes is not generally indicated unless BP control is not
achieved
Lifestyle Modification
Modification Approximate SBP
reduction
(range)
Weight reduction 5–20 mmHg/10 kg weight
loss
Adopt DASH eating 8–14 mmHg
plan
Dietary sodium 2–8 mmHg
reduction
Physical activity 4–9 mmHg
Moderation of alcohol 2–4 mmHg
consumption
Classes of
Antihypertensive Drugs
• ACE inhibitors
• Adrenergic inhibitors
• Angiotensin II receptor blockers
• Calcium antagonists
• Direct vasodilators
• Diuretics
Combination Therapies
• -adrenergic blockers and diuretics
• ACE inhibitors and diuretics
• Angiotensin II receptor antagonists and
diuretics
• Calcium antagonists and ACE inhibitors
• Other combinations
Followup
• Followup within 1 to 2 months after initiating
therapy.
• Recognize that high-risk patients often require high
dose or combination therapies and shorter intervals
between changes in medications.
• Consider reasons for lack of responsiveness if blood
pressure is uncontrolled after reaching full dose.
• Consider reducing dose and number of agents after
1 year at or below goal.
Pregnant Women
• Chronic hypertension is high blood pressure present
before pregnancy or diagnosed before the 20th week
of gestation.
• Preeclampsia is increased blood pressure that occurs
in pregnancy (generally after the 20th week) and is
accompanied by edema, proteinuria, or both.
• ACE inhibitors and angiotensin II receptor blockers
are contraindicated for pregnant women.
• Methyldopa is recommended for women diagnosed
during pregnancy.
Antihypertensive Drugs
Used in Pregnancy

These agents* may be used with chronic hypertension


(DBP > 100 mm Hg) or acute hypertension (DBP > 105 mm Hg).

Central -agonists Methyldopa is the drug of choice.

-blockers and Atenolol, metoprolol, and labetalol appear safe


--blockers and effective in late pregnancy.

Calcium antagonists Potential synergism with magnesium sulfate may lead


to precipitous hypotension.

*Limited or no controlled trials in pregnant women.


Antihypertensive Drugs
Used in Pregnancy (continued)

These agents* may be used with chronic hypertension


(DBP > 100 mm Hg) or acute hypertension (DBP > 105).

Diuretics Diuretics are recommended for chronic


hypertension if prescribed before gestation,
but they are not recommended for
preeclampsia.
Direct Hydralazine is the parenteral drug of choice
vasodilators based on its long history of safety and
efficacy.
*Limited or no controlled trials in pregnant women.

ACE inhibitors and angiotensin II receptor blockers are contraindicated.


Mechanism of Action of
Angiotensin II Receptor Antagonists
Angiotensinogen
Alternate
Bradykinin Angiotensin I pathways
ACE
inhibitors
Angiotensin II
Inactive
peptides AIIRAs
?
AT1 receptor Ot h
e
e pt or rece r AT
AT 2 rec ptor
s

Vasodilation
? Attenuate growth and
disease progression
Modifikasi Gaya Hidup untuk
Pengendalian Hipertensi
Modifikasi Rekomendasi Penurunan Tekanan
Darah Sistolik
kurang lebih
Menurunkan berat badan Pelihara berat badan normal 5-20 mm Hg utk
(BMI 18.5-24.9)
setiap penurunan
10 kg BB
Menjalankan menu DASH Konsumsi makanan kaya 8-14 mm Hg
buah, sayur, susu rendah
lemak dan rendah lemak
jenuh

Mengurangi asupan Kurangi natrium sampai 2-8 mm Hg


tidak lebih dari 2.4 g/hari
garam/sodium atau NaCl 6 g/hari

Meningkatkan aktifitas Berolah raga erobik teratur 4-9 mm Hg


seperti berjalan kaki
fisik (30 men/hari, 4-5 hari
seminggu)
Source: The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure JNCVII. JAMA. 2003;289:2560-2572.
ESH-ESC 2007
Antihypertensive drugs

• Alpha blockers Centrally acting agents


• Vasodilators
• Calcium Channel
Blockers Angiotensin Converting
•Angiotensin Enzyme Inhibitors
Receptor
Blockers

Beta Blockers
Diuretics
Sympatholytics
Centrally acting sympatholytics
Clonidine
α-methyldopa
Guanfacine
Guanabenz
Peripherally acting sympatholytics
Metyrosine
Guanethidine, Bretylium
Reserpine
Peripheral Sympatholytics
rarely used

Metyrosine (or α-methyl-tyrosine):

inhibits tyrosine hydroxylase

rate-limiting enzyme for NE


synthesis

Bretylium, Guanethidine

uptaken into NE vesicle

prevent NE release from vesicle

Reserpine

inhibits accumulation of NE into


vesicle
Direct acting vasodilators

Hydralazine
liberates NO from vascular endothelium
decreases TPR
not used as monotherapy
bioavailability dependent on genetic
factors
adverse effects: tachycardia, hypotension,
fluid retention, lupus-like syndrome
only used in severe or refractory
hypertension
Direct acting vasodilators
Minoxidil

prodrug of N-O sulfate

K+ channel opener, reduces smooth


muscle contractility

not used as monotherapy

long duration of action (~24 hours) Minoxidil

adverse effects: tachycardia, fluid


retention, hypertrichosis

only used in severe or refractory


hypertension
Thiazide Diuretics
mechanism of action

lower plasma volume

monotherapy for mild to


moderate hypertension
Hydrochlorothiazide
ALLHAT: reduction of CVD
superior to other agents

adjunct agent

most effective in patients with


normal kidney function
Drugs interacting with Renin-Angiotensin system

ACE inhibitors: inhibit Angiotensin II formation

Angiotension receptor antagonists: block Angiotensin receptor


activation
Systemic Effects of ACE inhibitors

Reduction in
total peripheral resistance
systolic and diastolic pressure
mean arterial pressure
aldosterone secretion
cardiac remodeling
Increase in
regional blood flow in vascular beds
large artery compliance
Types of ACE inhibitors
Active Molecules
Captopril (Capoten)
Lisinopril (Prinivil)
Enalaprilat
Prodrugs: Enalaprilat

must be biotransformed for


activity by esterases
•Enalapril (Vasotec)
•Fosinopril (Monopril)
•Quinapril (Accupril)
•Ramipril (Altace) Enalapril
Side Effects
hypotension
cough
hyperkalemia
angioedema
renal insufficiency
teratogenic
skin rash
neutropenia
proteinuria (protein in urine)
ageusia (loss of taste)
Types of AT1 receptor antagonists

Losartan (Cozaar)
competitive antagonist
Valsartan (Diovan)
non-competitive
Candesartan (Atacand)
non-competitive
Losartan
Irbesartan (Aprovel)
non-competitive
Therapeutic Uses
same uses as ACE inhibitors

excellent for inhibiting cell growth

no bradykinin effects

no cough

useful for hypertension secondary to CHF

used for prevention of re-stenosis after angioplasty


Adrenergic receptor antagonists
β-adrenergic receptor antagonists
“β-blockers”
Non-selective: Propranolol, Nadolol, Timolol, Pindolol,
Labetolol
Cardioselective: Metoprolol, Atenolol, Esmolol,
Betaxolol
α1-adrenergic receptor antagonists
“α-blockers”
Non-selective: Phentolamine, Phenoxybenzamine,
Dibenamine
Selective: Prazosin, Doxazosin, Terazosin
-blockers: Side Effects
Bradycardia
Bronchospasm
Coldness of extremities
Heart failure
Contraindicated in insulin-dependent diabetes
CNS effects
Increased plasma triglyceride concentration
Decreased plasma HDL concentration
Do not use in conjunction with Ca2+ channel
lockers, conduction effects in heart
NSAID’s blunt β-blocker effects
Ca2+ channel antagonists
an initial choice for monotherapy of mild to moderate
hypertension
all antagonists are equally effective for Stage 1
hypertension
Verapamil and Diltiazem do not cause reflex tachycardia
directly inhibit cardiac chronotropy
Effective in low-renin hypertension
African-americans
Elderly
Do not cause fluid retention
Hypertension in Women

 Oral contraceptives may increase BP, and BP should be


checked regularly. In contrast, HRT does not raise BP.

 Development of HTN—consider other forms of contraception.

 Pregnant women with HTN should be followed carefully.


Methyldopa, BBs, and vasodilators, preferred for the safety of
the fetus. ACEI and ARBs contraindicated in pregnancy.
Women
• Clinical trials have not demonstrated
significant differences between men and
women in treatment response and outcomes.
• Some women using oral contraceptives may
have significant increases in blood pressure.
• High blood pressure is not a contraindication
to hormone replacement therapy.
Pregnant Women
• Chronic hypertension is high blood pressure present
before pregnancy or diagnosed before the 20th week
of gestation.
• Preeclampsia is increased blood pressure that occurs
in pregnancy (generally after the 20th week) and is
accompanied by edema, proteinuria, or both.
• ACE inhibitors and angiotensin II receptor blockers
are contraindicated for pregnant women.
• Methyldopa is recommended for women diagnosed
during pregnancy.
Antihypertensive Drugs
Used in Pregnancy

These agents* may be used with chronic hypertension


(DBP > 100 mm Hg) or acute hypertension (DBP > 105 mm Hg).

Central -agonists Methyldopa is the drug of choice.

-blockers and Atenolol, metoprolol, and labetalol appear safe


--blockers and effective in late pregnancy.

Calcium antagonists Potential synergism with magnesium sulfate may lead


to precipitous hypotension.

*Limited or no controlled trials in pregnant women.


Antihypertensive Drugs
Used in Pregnancy (continued)

These agents* may be used with chronic hypertension


(DBP > 100 mm Hg) or acute hypertension (DBP > 105).

Diuretics Diuretics are recommended for chronic


hypertension if prescribed before gestation,
but they are not recommended for
preeclampsia.
Direct Hydralazine is the parenteral drug of choice
vasodilators based on its long history of safety and
efficacy.
*Limited or no controlled trials in pregnant women.

ACE inhibitors and angiotensin II receptor blockers are contraindicated.