PEMILIHAN OBAT

HIPERTENSI

Dr.Didiet Pratignyo,SpPD
RSUD Cilegon
10 Mei 2012
 Pembahasan

ÞDefinisi
ÞManifestasi klinik
ÞKerusakan organ
ÞGuidelines
ÞTujuan terapi
ÞAlgoritme management hipertensi
ÞTreatment farmakologi
 Apa yang dimaksud Hipertensi ?
“Tekanan darah arteri yang tinggi dan
menetap”

“The continuous relationship between the level of

blood pressure and cardiovascular risk makes any
numerical definition and classification of
hypertension arbitrary.” 1

1
2003 European Society of Hypertension-European Society of Cardiology guidelines for the
management of arterial hypertension. Journal of Hypertension 2003 vol21 no6 p1011-1063.
 Tekanan darah Sistolik & Diastolik
• Systolic Blood Pressure:
BP  when the heart contracts and “expels” the blood
into the arteries. This is what gives rise to the pulse,
known as the “maxima”
(Tekanan darah maksimal ketika darah dipompakan
dari ventrikel kiri)
• Diastolic blood pressure:
While the heart is filling between two contractions,
the blood in the main arteries flows towards the
smallest arteries: the blood pressure in the main
arteries then falls to the “minima”
(Tekanan darah pada saat jantung relaksasi)
Pengukuran Tekanan Darah

• Penderita duduk tenang di kursi

sedikitnya 5 menit, dengan posisi
kaki di lantai dan lengan pada
posisi setinggi jantung
• Pengukuran dilakukan sedikitnya
dua kali
Pemilihan Obat?
 Manifestasi klinik
• Asymptomatic pada sebagian besar
penderita. Dapat tidak terdeteksi untuk
beberapa tahun.

• Sakit kepala (headache) dapat terjadi

jika kenaikan tekanan darah sistolik
diatas 200 mmHg atau ketika tekanan
darah naik secara mendadak.
Consequences of Hypertension: Organ Damage

Hypertension

Transient ischemic
attack, stroke LVH, CHD, CHF

Peripheral
Retinopathy arterial Chronic kidney disease
disease
CHF=congestive heart failure; CHD=coronary heart disease; LVH=left ventricular hypertrophy.
Chobanian AV et al. JAMA. 2003;289:2560-2572.
KOMPLIKASI HIPERTENSI PADA MATA
 Guidelines Hipertensi

Ada dua guidelines, yang dipakai saat ini :

• 2003 European Society of Hypertension

(ESH)-ESC guidelines

• 2003 American Joint National Committee’s

seventh guidelines (JNC-7)
Stadium hipertensi (JNC V)
Kategori Sistolik Diastolik
(mmHg) (mmHg)
Normal tinggi(perbatasan) 130 - 139 85 - 89
Stadium I (ringan) 140 - 159 90 - 99
“ II (sedang) 160 - 179 100 - 109
“ III (berat) 180 - 209 110 - 119
“ IV (sangat berat) ≥ 210 ≥ 120

Classification and follow-up blood pressure measurenments (JNC VI)

Category Systolic BP Diastolic BP Follow-up
Recomended
(mmHg) (mmHg)
Optimal < 120 < 80 Recheck in 2 years
Normal < 130 < 85 Recheck in 2 years
High-normal 130 - 139 85 - 90 Recheck in 1 years
Hypertension
Stage 1(mild) 140 - 159 90 - 99 Confirm within 2 month
Stage 2(moderate) 160 - 179 100 - 109 Evaluate or refer within 1 month
Stage 3(severe) > 180 > 110 Evaluate or refer within 1 week
BP Classification Systolic Blood Pressure Diastolic Blood Pressure
ESH 2003
Optimal <120 <80
Normal 120-129 80-84
High Normal 130-139 85-89
Grade 1 HT (mild) 140-159 90-99
Grade 2 HT (moderate) 160-179 100-109
Grade 3 (severe) >180 >110
Isolated systolic HT >140 <90

JNC VII and

Normal <120 <80
120-139 or 80-89
Prehypertension or
Stage 1 HT 140-159 90-99
>160 or >100
Stage 2 HT
 JNC 7: Treatment Algorithm for Hypertension
Lifestyle modifications

Not at goal blood pressure (<140/90 mm Hg)

(<130/80 mm Hg for those with diabetes or chronic kidney disease)

Initial drug choices

Without compelling indications With compelling indications

Stage 1 hypertension Stage 2 hypertension Drugs for compelling indications

(SBP 140–159 or DBP 90–99 mm Hg) (SBP ³160 or DBP ³100 mm Hg) Other antihypertensive drugs
Thiazide-type diuretic for most. Two-drug combination for most (diuretic, ACEI, ARB, BB, CCB) as
May consider ACEI, ARB, BB, CCB, (usually thiazide-type diuretic and needed.
or combination. ACEI or ARB or BB or CCB).

Not at goal blood pressure

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

SBP=systolic blood pressure; DBP=diastolic blood pressure; ACEI=angiotensin-

converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=b-blocker;
CCB=calcium channel blocker
JNC 7. May 2003. NIH publication 03-5233.
 Lifestyle modifikasi
Þ Menurunkan berat badan
– Mempertahankan berat badan normal
• BMI: 18.5 – 24.9
• Menurunkan tekanan darah: 5-20 mmHg
• Mengurangi berat badan : 10 kg
Þ DASH Eating Plan
– Dietary Approaches to Stop Hypertension
• Buah
• Sayur
• Diet rendah lemak
 Tujuan Terapi

• Reduction of cardiovascular and renal

morbidity and mortality. 1

• The primary focus should be on achieving the

systolic BP goal.
• Systolic BP and diastolic BP to targets < 140/90
mmHg = decrease in CVD complications.
• In patients with hypertension with diabetes or renal
disease, the BP goal is < 130/80 mmHg 1

1
JNC - VII Report, JAMA , 2003;289:2560-2572
 Pilihan obat antihipertensi
• Diuretics, beta-blockers, calcium antagonists, ACE-inhibitors,
angiotensin receptor antagonists) disesuaikan untuk terapi awal
dan pemeliharaan
• Pertimbangan :
® Pengalaman penderita terdahulu
® Beaya
® Profil risiko, kerusakan target organ, adanya penyakit
kardiovaskular, penyakit ginjal atau diabetes
® Yang disukai penderita

• Preparat long acting pemberian sekali sehari dengan efikasi

24 jam merupakan dasar pilihan
 Pertimbangan khusus
Guideline Basis for Compelling Indications for Individual
Drug Classes

High Risk Conditions Recommended Drugs

With Compelling
Indication
Diuretic -blocker ACE inhibitor ARB CCB Aldosterone Antagonist
Heart failure

Post-myocardial infarction

High coronary disease risk

Diabetes

Chronic Kidney Disease

Recurrent stroke prevention

JNC - VII Report, JAMA , 2003;289:2560-2572

 GUIDELINE RECOMMENDATION

ACE Angiotensin II Calcium Aldosterone

Diuretic -blocker Inhibitor Blocker Antagonists Antagonist

Heart Failure     

Post Heart Attack    

High CAD Risk     

Diabetes Mellitus     

Chronic Renal
Disease  
 New studies
Recurrent Stroke   

Modified from Chobanian AV, et al. JAMA 2003;289:2560-2572.

PATOFISIOLOGI
 Neurohormonal control of blood pressure
Blood Presure = Cardiac Output X Peripheral Resistance
Hypertension = Increased CO and/or Increased PR

↑ Preload Contactility Vasoconstriction

Heart Rate ↑

↑ Fluid Volume Sympathetic

Nervous
System RAAS
Renal
Excess Sodium Genetic
Sodium
Intake Alteration
Retention
 Angiotensinogen

Tissue renin

Cathepsin G
Angiotensin I
Bradykinin Elastase
Tissue ACE
ACE TPA
Chymase
Cathepsin G
Peptide

Angiotensin II
ARBs

AT1R AT2R
Sisi kerja obat anti HT
 Interaction with the Calcium Receptor
1 High vascular
Extra-Cellular Space selectivity
Ca2+
1 2
High lipophilicity
strong binding
to cell membrane

2 5
3 Gradual diffusion
towards calcium
channels

4 Fixation on calcium
3 channel receptors
4
5 Progressive and
continuous
calcium inhibition
Calcium Channel (VOC) Intra-Cellular Space
Balance Dilation of Afferent & Efferent
Oral antihypertensive drugs
1

Class Drug (Trade Name) Usual dose range in mg/day

(daily frequency)

Thiazide diuretics Chlorothiazide (Diuril) 125 - 500 (1)

Chlorthalidone (Generic) 12.5 - 25 (1)
Hydrochlorothiazide 12.5 - 50 (1)
(Microzide, HydroDIURIL)
Polythiazide (Renese) 2 - 4 (1)
Idapamide (Lozol) 1.25 – 2.5 (1)
Metolazone (Mykrox) 0.5 – 1.0 (1)
Metalozano (zaroxylyn) 2.5 – 5 (1)

Loop diuretics Bumetanide (Bumex) 0.5 – 2 (20 )

Furosemide (Lasix) 20 – 80 (2)
Torsemide (Demadex) 2.5 – 10 (1)
JNC VII, 2003
Oral antihypertensive drugs
2
Usual dose range in
Class Drug (Trade Name) mg/day (daily
frequency)

Beta-blockers Atenolol (Tenormin) 25 – 100 (1)

Betaxolol (Kerlone) 5 – 20 (1)
Bisoprolol (Zebeta) 2.5 – 10 (1)
Metoprolol (Lopressor) 50 – 100 (1-2)
Metoprolol extended release (Toprol 50 – 100 (1)
XL)
Nadolol (Corgard) 40 – 120 (1)
Propranolol (Inderal) 40 – 160 (2)
Propranolol long-acting (Inderal LA) 60 – 180 (1)
Timolol (Blocadren) 20 – 40 (2)

Beta-blockers with Acebutolol (Sectral) 200 – 800 (2)

intrinsic Penbutolol (Levatol) 10 – 40 (1)
JNC VII, 2003
Oral antihypertensive drugs
3

Class Drug (Trade Name) Usual dose range in mg/day

(daily frequency)

ACE inhibitors Benazepril (Lotensin) 10 -40 (1-2)

Captopril (Capoten) 25 – 100 (2)
Enalarpil (Vasotec) 2.5 – 40 (1-2)
Fasinopril (Monopril) 10 – 40 (1)
Lisinopril (Prinvil, Zestril) 10 – 40 (1)
Moexipril (Univasc) 7.5 – 30 (1)
Perindropril (Aceon) 4 – 8 (1-2)
Quinapril (Accupril) 10 – 40 (1)
Ramipril (Altace) 2.5 – 20 (1)
Trandolapril (Mavik) 1 – 4 (1)

JNC VII, 2003

Oral antihypertensive drugs
4
Usual dose range in
Class Drug (Trade Name) mg/day (daily
frequency)

Calcium channel Diltiazem extended release 180 – 420 (1)

blockers- non- (Cardizem CD, Dilacor XR, Tiazac) 120 – 540 (1)
Dihydropyridines Diltiazem extended release (Cardizem LA) 80 – 320 (1)
Verapamil immediate release (Calan,
Isoptin SR) 120 – 360 (1-2)
Verapamil – Coer (Covera HS, Verelan
PM) 120 – 360 (1)

Calcium channel Amlodipine (Norvasc) 2.5 – 10 (1)

blockers- Felodipine (Plendil) 2.5 – 20 (1)
Dihydropyridines Isradipine (Dynacirc SR) 2.5 – 10 (2)
Nicardipine sustained release (Cardene 60 – 120 (2)
SR)
Nifedipine long-acting (Adalat CC, 30 – 60 (1)
JNC VII, 2003
Oral antihypertensive drugs 5

Usual dose range in

Class Drug (Trade Name) mg/day (daily
frequency)

Alpa1, blockers Doxazosin (Cardura) 1 – 16 (1)

Prazosin (Minipress) 2 – 20 (2 – 3)
Terazosin (Hytrin) 1 – 20 (1 – 2)

Central alpha2 agonist and Clonidine (Catapres) 0.1 – 0.8 (20

other centrally acting Clonidine patch (Catapres-TTS) 0.1 – 0.3 (1 wkly)
drugs Methyldopa (Aldoment1) 250 – 1.000 (2)
Reserpine (generic) 0.05 – 0.25 (1)
Guanfacine (generic) 0.5 – 2 (1)

JNC VII, 2003

Indication and contraindications for the major classes of
antihypertensive drugs 1
Contraindications
Class Conditions favouring the use Compelling Possible

Diuretics (thiazides) Congestive heart failure; elderly Gout Pregnancy

hypertensive ; isolated systolic
hypertension ; hypertensives of
African origin

Diuretics (loop) Renal insufficiency ; congestive

heart failure

Diuretics (Anti- Congestive heart failure ; post- Renal failure ;

aldosterone) myocardial infarction hyperkalemia

-Blockers Angina pectoris ; post-myocardial Asthma ; chronic Peripheral vascular

infarction ; congestive heart obstructive disease ; glucose
failure (up-titration); pregnancy ; pulmonary disease intolerance ;
tacthyarrhythmias ; A-V block (grade athletes and
2 or 3) physically active
patients.
Journal of Hypertension 2003, Vol. 21 No. 6
Indication and contraindications for the major classes of
antihypertensive drugs 2
Contraindications
Class Conditions favouring the use Compelling Possible

Calcium Angina pectoris ; carotid A-V block (grade

antagonists atherosclerosis; supraventricular 2 or 3) ;
(verapamil, tachycardia congestive heart
diltiazem) failure

Angiotension- Congestive heart failure ; LV Pregnancy ;

converting dysfunction ; post-myocardial hyperkalemia ;
enzyme (ACE) infarction ; non-diabetic bilateral renal
inhibitors nephropathy ; type 1 diabetic artery stenosis
nephropathy proteinuria.

Journal of Hypertension 2003, Vol. 21 No. 6

MECHANISM OF ACTION : ACE I vs ARB

Angiotensinogen
Renin
ACEI
Angiotensin I Bradikinin Batuk
Jalur Non-ACE
Cth: khimase ACE
Angiotensin II
ARB Fragmen
inaktif
Reseptor AT1 Reseptor AT2

 Sekresi Aldosteron  Vasodilatasi

 Vasokonstriksi  Antiproliferasi (kinin)

Tekanan darah naik Tekanan darah turun

The Renin Angiotensin System: AT1 Blockade

Angiotensin I
ACE
ARB
Angiotensin II

AT1 AT2 B2 NO, PGI2

Vasoconstriction
Antiproliferation Vasodilation, etc
Differentiation
Proliferation
Regeneration
Aldosterone
Sympathetic NS
Anti-Inflammation NO
NaCl-Retention
Apoptosis? Vasodilation
Inflammation Tissue protection
Apoptosis
Adapted from Unger & Stoppelhaar 2007
Effects of Angiotensin II in the kidney
 The Cardiovascular Continuum
Coronary Artery ARB
ARB Disease
Plaque Rupture
Atherosclerosis
ARB

Endothelial Dysfunction Myocardial Infarction

Dilatation/Remodeling
Risk Factors
ARB
Heart Failure ARB
Hypertension
Hyperlipidemia End-Stage Heart Disease
Diabetes
Post test

1. Definisi Hipertensi pada individu non DM :

a) TDS ≥140 dan/atau TDD ≥ 90 mmHg
b) TDS ≥120 dan/atau TDD ≥80 mmHg
c) TDS ≥130 dan/atau TDD ≥80 mmHg
d) TDS ≥110 dan/atau TDD ≥70 mmHg

2. Definisi Hipertensi pada individu DM :

a) TDS ≥140 dan/atau TDD ≥90 mmHg
b) TDS ≥120 dan/atau TDD ≥80 mmHg
c) TDS ≥130 dan/atau TDD ≥80 mmHg
d) TDS ≥110 dan/atau TDD ≥70 mmHg
3. Definisi Hipertensi sistolik (ISH) :
a) TDS ≥140 dan/atau TDD ≥90 mmHg
b) TDS ≥120 dan/atau TDD ≤80mmHg
c) TDS ≥130 dan/atau TDD ≤80mmHg
d) TDS ≥110 dan/atau TDD ≤70 mmHg
4.Pemilihan pada kasus hipertensi + kehamilan :
a) BB b) CCB c) ACE-I d) ARB e) Diuretik
f) Metildopa
5.Pemilihan antihipertensi pada usia tua :
a) BB b) CCB c) ACE-I d) ARB e) Diuretik
6. Pemilihan antihipertensi pada kasus hipertensi +
gagal jantung kongestif :

a) BB b) CCB c) ACE-I d) ARB e) Diuretik

7. Pemilihan pd kasus hipertensi + pasca IMA &AF:
a) BB b) CCB c) ACE-I d) ARB e) Diuretik

8. Pemilihan antihipertensi pads kasus hipertensi +

penyakit ginjal kronik (CKD) :
a) BBb) CCB c) ACE-I d) ARB e) Diuretik
9. Pemilihan antihipertensi pads kasus hipertensi +
angina :
a) BBb) CCB c) ACE-I d) ARB e) Diuretik

10. Pemilihan antihipertensi pads kasus hipertensi +

disfungsi ventrikel kiri :
a) BBb) CCB c) ACE-I d) ARB e) Diuretik
Ringkasan
Þ HT asymptomatic, kontrol secara rutin

Þ Diagnosis dini – Untuk mencegah - Risiko kardio-

vaskuler dan kerusakan target organ

Þ Tekanan darah < 140/90 mmHg = menurunkan

risiko penyakit kardiovaskuler

Þ HT pada diabetes atau penyakit ginjal, tekanan

darah < 130/80 mmHg
Terima
kasih