ANTIHIPERTENSI

Dr. M. Yulis Hamidy, M.Kes., M.Pd.Ked

REGULASI TEKANAN DARAH

REFLEKS BARORESEPTOR

CO

Denyut
jantung
Isi
sekuncup

Kontraktilitas
miokard

Alir balik
vena
TEKANAN
DARAH
Resistensi
Pmblh darah
Resistensi
Perifer

Viskositas
darah

Parasimpatis

Tonus arteri
& arteriol

Volume
Darah
Kapasitas
vena

Elastisitas dinding
Pembuluh darah
SEKRESI RENIN

Simpatis

RAA

KRITERIA HIPERTENSI

ETIOLOGI HIPERTENSI

90% tidak diketahui penyebabnya

hipertensi esensial
10%:

Penyakit Ginjal
Tumor Endokrin

Hipertensi esensial:
- Faktor genetik berperan besar
- Faktor eksternal:

Stressful Lifestyle
Intake Sodium
Obesitas
Smoking

TERAPI HIPERTENSI

Tujuan terapi: menurunkan morbiditas &

mortalitas
Sasaran tekanan darah:
Muda < 140/90
Lansia/80 tahun < 160/90
Resiko yang diakibatkan hipertensi

CHF
Kerusakan Ginjal
Kerusakan Cerebrovascular
Penyakit Retina

STRATEGI TERAPI HIPERTENSI

Non farmakologis & farmakologis
- Hipertensi ringan modifikasi gaya hidup, diet
rendah garam
- Hipertensi sedang + 1 jenis obat antihipertensi
- Hipertensi berat biasanya + kombinasi 2/3
obat tergantung kondisi pasien
Pendekatan individual
Hipertensi pada pasien sering disertai adanya
penyakit lain, pilih antihipertensi yang tepat
Kepatuhan penderita
Sangat menentukan keberhasilan
Pengontrolan tensi terus menerus

PRINSIP TERAPI HIPERTENSI

Nonpharmacological therapy is an
important component of treatment of all
patients with hypertension
In some stage 1 hypertensives, blood
pressure may be adequately controlled by a
combination of:

Weight loss (in overweight individuals)

Restricting sodium intake
Increasing aerobic exercise
Moderating consumption of alcohol

TERAPI NONFARMAKOLOGIS

REDUCTION OF BODY WEIGHT

SODIUM RESTRICTION
ALCOHOL RESTRICTION
PHYSICAL EXERCISE
RELAXATION AND BIOFEEDBACK THERAPY
POTASSIUM THERAPY
TOBACCO, COFFEE, AND OTHER FACTORS

MEKANISME ANTIHIPERTENSI

Arterial pressure is the product of cardiac output and

peripheral vascular resistance
Drugs lower blood pressure by actions on peripheral
resistance, cardiac output, or both
Drugs may reduce the cardiac output by inhibiting myocardial
contractility or by decreasing ventricular filling pressure
Reduction in ventricular filling pressure may be achieved by
actions on the venous tone or on blood volume via renal
effects
Drugs can reduce peripheral resistance by acting on smooth
muscle to cause relaxation of resistance vessels or by
interfering with the activity of systems that produce
constriction of resistance vessels (e.g., the sympathetic
nervous system)

OBAT ANTI HIPERTENSI

ANTI HIPERTENSI PILIHAN PERTAMA

1.
2.
3.
4.
5.

DIURETIKA
BETA BLOKER
ACE INHIBITOR
Ca ANTAGONIS
ALFA BLOKER

ANTI HIPERTENSI TAMBAHAN

1.
2.
3.

ALFA 2 AGONIS
PENGHAMBAT ADRENERGIK
VASODILATOR

KLASIFIKASI OAH MENURUT

TEMPAT & MEKANISME KERJANYA
A. DIURETIK
1. Thiazid & sejenisnya
2. Diuretik kuat (loop diuretic)
3. Diuretik hemat kalium
B. OBAT SIMPATOLITIK
1. Adrenolitik sentral
2. Penghambat saraf adrenergik
3. Penghambat adrenergik
4. Penghambat adrenergik
5. Penghambat mixed (,) adrenergik
C. VASODILATOR
1. Arteri
2. Arteri & vena
D. Ca2+ ANTAGONIS
E. ACE INHIBITOR
F. ANTAGONIS RESEPTOR ANGIOTENSIN II

A. DIURETIK
MEKANISME ANTIHIPERTENSI
Ekskresi Na, Cl, air volume plasma
& cairan ekstrasel
Curah jantung normal
Resistensi perifer pemakaian
kronik

A. DIURETIK
1. Tiazid
Obat tunggal hipertensi ringan-sedang
Baik digunakan kombinasi dengan OAH lain
Efek menurun oleh AINS & gagal ginjal
Murah, bisa 1x/hari, efek lama
ES:

Hipo: kalemia, Mg, Na

Hiper: kalsemia, urisemia, glikemia, kolesterol
& trigliserida

Gangguan seksual
Toksisitas digitalis meningkat

A. DIURETIK
2. Diuretik kuat (furosemid)
Efektif untuk hipertensi dengan gagal
ginjal & gagal jantung
ES = tiazid kecuali hiperkalsemia
3. Diuretik hemat kalium (spironolakton)
Diuretik lemah
Hiperkalemia
Efek hipotensi sebanding hidroklortiazid

B. SIMPATOLITIK
1. ADRENOLITIK SENTRAL

Klonidin

Resistensi perifer , denyut jantung

normal
Pilihan II, kombinasi diuretika &
vasodilator
Sediaan parenteral untuk krisis
hipertensi
ES: sedasi, mulut kering, konstipasi,
retensi cairan, reaksi putus obat
(hentikan bertahap)

ADRENOLITIK SENTRAL

Metildopa

Resistensi perifer , denyut jantung

normal
Pilihan I hipertensi pada ibu hamil
Absorpsi tak lengkap, bioavailabilitas
25-50%, efek hipotensi maksimal 6-8 jam
setelah dosis oral
ES: sedasi, hipotensi postural, pusing,
sakit kepala (SSP), fenomena rebound

Guanefasin & guanebenzen

Efek & ES mirip klonidin

SIMPATOLITIK
2. PENGHAMBAT SARAF ADRENERGIK

Prototip: reserpin
Resistensi perifer , denyut & curah jantung
Mula kerja lambat, masa kerja panjang
Hipertensi ringan-sedang, kombinasi tiazid
Murah 1x sehari (0,25 mg)
ES: depresi mental, disfungsi seksual, mimpi buruk,
sekresi asam lambung, mual, muntah, diare, mulut
kering, ambang kejang turun, efek ekstra piramidal,
bradikardi
Obat lain:
- Guanetidin, jarang digunakan karena ES
hipotensi ortostatik & diare
- Guanadrel, mirip guanetidin

SIMPATOLITIK
3. PENGHAMBAT ADRENERGIK

Prototip: propranolol
Denyut jantung menurun, resistensi perifer
Menghambat pelepasan norepinefrin prasinap
Menghambat sekresi renin (1 ginjal)
Efek sentral, pilihan I hipertensi ringan-sedang
Efektif untuk usia muda
Kardioselektif, ISA (+) kurang efektif untuk MCI
ES & kontra indikasi: bronkospasme, asma
bronkial, DM, gagal ginjal, penyakit vaskuler

SIMPATOLITIK
4. PENGHAMBAT ADRENERGIK

Alfa 1 selektif: prazosin, terazosin, doksazosin,

bunazosin
Dilatasi arteriol resistensi perifer refleks
takikardi normal
Efek baik terhadap lipid darah (LDL & TG , HDL
meningkat)
Resistensi insulin menurun
Tak ada interaksi dengan AINS
Bronkodilatasi, relaksasi prostat, tidak
mengganggu aktivitas fisik
ES: hipotensi ortostatik, sakit kepala, lelah,
edema, hidung tersumbat, nausea, dll

SIMPATOLITIK
5. KOMBINASI PENGHAMBAT 1, ADRENERGIK

Obat: labetalol, carvedilol

Labetalol: resistensi vaskuler
tekanan arteri , CO tetap, IV
untuk hipertensi emergensi
Carvedilol
ratio

1- adrenergik reseptor antagonis

= 1:10
indikasi: hipertensi esensial & disfungsi
sistolik

C. VASODILATOR

Hidralazin

Dilatasi arteriol > Vena

Kombinasi dengan diuretika & beta bloker
ES: retensi Na & air, takikardi, sindroma lupus,
neuropati perifer, diskrasia darah, hepatotoksik
Kontra indikasi: aneurisma aorta dissecting

Minoksidil

Permeabilitas K+ meningkat hiperpolarisasi

Poten untuk hipertensi refrakter

C. VASODILATOR
o

Diazoksid
o

o
o
o

Aktivasi kanal K+ (ATP) hiperpolarisasi

dilatasi arteriol denyut jantung
Efektif: hipertensi ensepalopati, hipertensi
berat, pre eklamsia (IV)
T 20-60 jam, efek hipotensi 4-20 jam
Ekskresi: ginjal (1/3), hati (2/3)
ES: retensi cairan & hiperglikemia, hipotensi,
takikardi, iskemia, mual, muntah, relaksasi
uterus

C. VASODILATOR
o

Natrium nitroprusid
o

o
o

NO mengaktifkan guanilat siklase otot polos

pembuluh darah dilatasi arteriol & venule
Pilihan untuk krisis hipertensi, lebih poten dari
diazoksid, hidralazin & minoksidil
Infus IV , kerja maksimal 1-2 menit, cepat
hilang, dosis rata-rata 3 g/kg/menit
ES: hipotensi, mual, muntah, muscle twitching
Efek toksik akibat konversi menjadi sianida &
tiosianat, diperburuk oleh hipoksemia arteri
pada penderita PPOK, hipertensi rebound

D. Ca2+ ANTAGONIS
I. Verapamil, Diltiazem, Nifedipin
II. Nikardipin, Isradipin, Felodipin, Amlodipin
Golongan DHP (N, NK, I, F, A): vaskuloselektif, resistensi
perifer , efek jantung (-), aman dikombinasikan dengan
beta bloker
Bioavailabilitas oral rendah
Metabolisme lintas pertama amlodipin tinggi
Kadar puncak cepat dicapai iskemik miokardium
Absorbsi amlodipin lambat, TD turun perlahan
T pendek kecuali amlodipin 24 jam
I & A tidak meningkatkan digoksin
Metabolisme di hati, ekskresi di ginjal
ES: hipotensi, edema perifer, bradiaritmia, gangguan
konduksi, konstipasi, penghentian mendadak infark
miokard

E. ACE INHIBITOR

Resistensi perifer , tanpa refleks takikardi

Efektif untuk hipertensi ringan-berat, hipertensi
mendesak
Kombinasi diuretika (sinergis)
Menurunkan resistensi insulin
Efek hipotensi dilawan oleh AINS
ES: batuk kering, rash, gangguan pengecapan,
hipotensi, edema angioneurotik, hiperkalemia,
GGA
Kontra indikasi kehamilan trimester 2-3 (GGA,
fetus mati)
Obat: Captopril, Enalapril, Lisinopril

E. ACE INHIBITOR
FARMAKOKINETIK
a. Captopril

Bioavailabilitas 60-65%, diturunkan oleh makanan

berikan 1 jam ac

Ikatan protein plasma 30%, T 2,2 jam, ekskresi

melalui urin 40%
b. Enalapril Enalaprilat (aktif)

Bioavailabilitas 40%, tidak dipengaruhi oleh makanan

T 11 jam, ekskresi melalui urin

c. Lisinopril

Bioavailabilitas 30-50%, tidak dipengaruhi oleh makanan

Tidak terikat protein plasma, T 12 jam, ekskresi

melalui urin

MEKANISME KERJA ACE INHIBITOR

& ANTAGONIS RESEPTOR
Angiotensinogen
Renin

Kininogen
Kalikrein

sintesis
Prostaglandin
Angiotensin I
Bradikinin
1
Converting enzyme (kininase II)
Angiotensin II
Inaktif
2
Vasokonstriksi
Sekresi aldosteron
Vasodilator
Resistensi vascular
Retensi air &
Perifer
natrium
Resistensi vaskuler
perifer menurun
Tekanan darah
Tekanan darah
1. Titik tangkap ACE inhibitor, 2. Titik tangkap antagonis reseptor

F. ANTAGONIS RESEPTOR
ARB (Angiotensin Reseptor Blocker)
Irbesartan (Avapro)R, Losartan (Cozar)R,
Valsartan (Diovan)R
o Mekanisme kerja: memblok pada tempat
pengikatan angiotensin II (reseptor AT
yang ada di pembuluh darah dan
jaringan)
o Efektifitas ~ ACE inhibitor
o Efek samping sedikit karena metabolisme
bradikinin dan prostaglandin tidak
terpengaruhi

SELECTION OF ANTIHYPERTENSIVE
DRUGS IN INDIVIDUAL PATIENTS

Recent guidelines recommend diuretics as preferred initial

therapy for most patients with uncomplicated stage 1
hypertension who are unresponsive to nonpharmacological
measures.
Patients are also commonly treated with other drugs: receptor
antagonists, ACE inhibitors/AT1-receptor antagonists, and
Ca2+ channel blockers.
Patients with uncomplicated stage 2 hypertension will likely
require the early introduction of a diuretic and another drug
from a different class.
Subsequently, doses can be titrated upward and additional
drugs added in order to achieve goal blood pressures (blood
pressure <140/90 mm Hg in uncomplicated patients).
Some of these patients may require four different drugs to
reach their goal.

SELECTION OF ANTIHYPERTENSIVE
DRUGS IN INDIVIDUAL PATIENTS

A most important and high-risk group of patients

with hypertension are those with compelling
indications for specific drugs on account of other
underlying serious cardiovascular disease (heart
failure, postmyocardial infarction, or with high risk
for coronary artery disease), chronic kidney disease,
or diabetes (Chobanian et al., 2003).
A hypertensive patient with congestive heart failure
ideally should be treated with a diuretic, receptor
antagonist, ACE inhibitor/AT1 receptor antagonist,
and spironolactone because of the benefit of these
drugs in congestive heart failure, even in the
absence of hypertension.

SELECTION OF ANTIHYPERTENSIVE
DRUGS IN INDIVIDUAL PATIENTS

ACE inhibitors/AT1 receptor antagonists should be

first-line drugs in the treatment of diabetics with
hypertension in view of their well-established benefits
in diabetic nephropathy.
A hypertensive patient with symptomatic benign
prostatic hyperplasia might benefit from having an 1
receptor antagonist as part of his therapeutic
program, since 1 antagonists are efficacious in both
diseases.
A patient with recurrent migraine attacks might
particularly benefit from use of a receptor antagonist
since a number of drugs in this class are efficacious in
preventing migraine attacks.

SELECTION OF ANTIHYPERTENSIVE
DRUGS IN INDIVIDUAL PATIENTS

Patients with isolated systolic

hypertension (systolic blood
pressure >160 mm Hg and diastolic
blood pressure <90 mm Hg) benefit
particularly from diuretics and also
from Ca2+ channel blockers.

SELECTION OF ANTIHYPERTENSIVE
DRUGS IN INDIVIDUAL PATIENTS

These considerations have been addressed with

regard to patients with hypertension that need
treatment to reduce long-term risk, not patients in
immediately life-threatening settings due to
hypertension.
Rapid reduction in blood pressure has considerable
risks for the patients; if blood pressure is decreased
too quickly or extensively, cerebral blood flow may
diminish due to adaptations in the cerebral
circulation that protect the brain from the sequelae
of very high blood pressures.