HIPERTENSI

Disusun Oleh:
Chemayanti
Surbakti
Fatimah Syam
Khairunnisa
Rambe
Yustika Rahayu
Richa Melisa

Taufik
Febrianto
M. Fadilah
Herry Febrian
Neni Arofiani

Prevalence of Cardiovascular Disease

Estimated Number of Persons With
Cardiovascular Disease in the US
10

Prevalence (millions)
20
30
40

12,200,000

CHF

4,600,000

Stroke

4,400,000

Other

60

50,000,000 (24%)

High BP
CAD

50

2,800,000

BP=blood pressure, CAD=coronary artery disease, CHF=congestive heart failure

American Heart Association . 2000

Heart andSKV-HIPERTENSI
Stroke Statistical Update.
FARMAKOTERAPI
2 1999.

Hypertensives Within Age

Group (%)

Age Distribution of Hypertensives in US

Population
(NHANES
III and the 1991 Census)
30
26%
74%
25
20
15

47.4 million
hypertensives
26.0% of US
population

21.3

19.2

13

9.5

10
5

23.7

9.6

3.7
18-29

30-39

40-49

50-59

60-69

70-79

Age Groups (y)

Franklin SS. J Hypertension. 1999;17(suppl
5):S29-S36.
FARMAKOTERAPI SKV-HIPERTENSI

80+

Ascultatory method of
blood pressure measurement

Nokolai Korotkoff, 1905

4

Blood Pressure (Tekanan Darah)

Tekanan yg ditimbulkan aliran darah
thd dinding pembuluh darah
Dinyatakan sebagai - systolic dan
diastolic
Systol = Tekanan tertinggi &
dihubungkan dgn kontraksi ventrikel
Diastol = tekanan terendah &
dihubungkan dgn relaksasi ventikel.

BP = CO X TPR
BP = Blood Pressure
CO (Q) = Cardiac Output
SV = Stroke Volume
HR= Heart Rate
TPR

= Total Peripheral Resistance

Faktor-faktor yang mempengaruhi

tekanan darah
End diastolic volume
End systolic volume
hormon

Saraf otonom

HR

Kontraktilitas otot
Volume
sekuncup

Curah jantung
Tekanan darah

Diameter
arteriol
TPR

Viskositas
darah

ESH 2003 & JNC VII(2003)

JNC 7
2003

ESC 2003

ESH-ESC 2003
BP Classification

BP

BP

Optimal

<120 / <80

<120/<80

Normal

120-129 / 8084

120-129 /8084

Prehypertensi
on

High normal

130-139 / 8589

130-139 /
85-89

Prehypertensi
on

Grade 1
Hypertension
(mild)

140-159 / 9099

140-159 /
90-99

Stage 1
Hypertension

Grade 2
Hypertension
(moderate)

160-179 /
100-109

>160 / >100

Stage 2
Hypertension

Grade 3
Hypertension
(severe)

> 180 / >110

Isolated Systolic

> 140

< 90

JNC VII(2003)
Bp
Classification
Normal

Isolated

Etiologi
Essential Hypertension
hypertension with no apparent cause 90-95%

Secondary Hypertension
hypertension of known cause

chronic renal diseases

2.5-5%
Renovascular diseases
0.5-4%
Oral contraceptive pills
0.2-1%
Coarctation of the Aorta
0.1-1%
Primary aldosteronism0.1-0.5%
Pheochromocytoma
0.1-0.2%

FAKTOR PENYEBAB
HIPERTENSI

Obesitas (Kelebihan Berat Badan)

Diet (Intake) Sodium berlebihan
Aktivitas Fisik yang rendah
Konsumsi buah, sayuran, potasium
rendah
Konsumsi alkohol yang berlebihan

KRISIS HIPERTENSI

Krisis hipertensi
Suatu keadaan peningkatan tekanan
darah yang mendadak (sistole 180
mmHg dan/atau diastole 120
mmHg), pd penderita hipertensi, yg
membutuhkan
penanggulangan
segera.
13

KLASIFIKASI KRISIS HIPERTENSI

1. Hipertensi emergensi
Kenaikan TD mendadak yg disertai
kerusakan organ target yang
progresif. Di perlukan tindakan
penurunan TD yg segera dalam
kurun waktu menit/jam.
2. Hipertensi urgensi
Kenaikan TD mendadak yg tidak
disertai kerusakan organ target.
14

Risk Factor

Age
Gender
Race
Genetic factors

Other:
obesity
high alcohol intake
high Na intake
abnormal renin values
high stress level
low birth weight
drugs

Complications of Hypertension:

Hypertension
is a risk factor
TIA, stroke

LVH, CHD,
HF

Retinopathy

Peripheral vascular
disease

Renal
failure

16

Gejala dan Tanda tekanan darah

tinggi
Mayoritas orang-orang yang menderita hipertensi ringan dan
sedang tidak
peduli akan kondisi mereka. Gejala-gejala hipertensi antara lain
adalah :
1. Kelelahan
2. Kebingungan
3. Mual dan muntah
4. Berkeringat berlebihan
5. Kulit merah atau pucat
6. Mimisan
7. Gelisah
8. Denyut jantung kuat, tidak beraturan
9. Telinga berdengung
10.Kelainan Ereksi
11.Sakit kepala
FARMAKOTERAPI SKV-HIPERTENSI

17

Pemeriksaan laboratorium
Pemeriksaan laboratorium rutin yang direkomendasikan
Sebelum memulai terapi antihipertensi adalah urinalysis,
kadar gula darah dan hematokrit; kalium, kreatinin, dan
kalsium serum; profil lemak (setelah puasa 9 12 jam)
termasuk HDL, LDL, dan trigliserida,Serta
elektrokardiogram.
Pemeriksaan opsional termasuk pengukuran ekskresi albumin
urin atau rasio albumin / kreatinin. Pemeriksaan yang lebih
ekstensif Untuk mengidentifikasi penyebab hipertensi tidak
diindikasikan Kecuali apabila pengontrolan tekanan darah
tidak tercapai.
kegunaan data Lab:
Mengindikasikan apakah terjadi efek HT ke organ target,
faktor risiko
dislipidemia, intoleransi glukose ke arah DM; dsb
FARMAKOTERAPI SKV-HIPERTENSI

18

Tes

Alasan

Urinalisis untuk darah dan

protein,
Elektrolit, kreatinin darah,
cystatin C

Dapat menunjukkan penyakit ginjal baik

Sebagai
penyebab, atau disebabkan oleh hipertensi
atau
(jarang) dapat dianggap hipertensi sekunder

Glukosa darah

Untuk mengetahui diabetes atau intoleransi

glukosa

Kolesterol HDL dan kolesterol

total
Serum

Untuk membantu memperkirakan risiko

kardiovaskular di masa depan

EKG

Membantu menetapkan adanya hipertrofi

pada
Ventrikel Kiri
Faktor resiko independen dalam perkembangan penyakit vaskular dini :
- Usia lanjut
- Peningkatan kolesterol total serum
- Penurunan kadar HDL serum
- Peningkatan glukosa serum
- Perokok
- Hipertrofi ventrikel kiri

FARMAKOTERAPI SKV-HIPERTENSI

19

Algorithm for Treatment of

Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling
Indications

Stage 1 HTN (SBP 140159

or DBP 9099 mmHg)
Thiazide-type diuretics for
most.
May consider ACEI, ARB, BB,
CCB, or combination.

Stage 2 HTN (SBP >160 or

DBP >100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic
and
ACEI, or ARB, or BB, or CCB)

With Compelling
Indications

Drug(s) for the compelling

indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB,
CCB)
as needed.

Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension
specialist. JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

"The Goal is to Get to Goal!

Hypertension

< 140/90 mmHg

-PLUSDiabetes or Renal Disease

< 130/80 mmHg

Patients should return for follow-up and

adjustment of medications every 1-2 months until

the BP goal is reached

TERAPI HIPERTENSI
Non-Farmakologi
Intake Na+
BB
intake alkohol
Olaha raga teratur
/hentikan merokok
Stres
Batasi agen2 yang
menginduksi hipertensi
Kontrasepsi oral
Simpatomimetik

Farmakologi (drug
therapy)
Diuretik
Mempengaruhi simpatetik
Central acting agent
Adrenergik blocking agent
Antagonis alfa
Antagonis beta
Antagonis campuran alfabeta
Direct vasodilator (termasuk
CaCB)
Mempengaruhi RAS
ACEIs

Lifestyle Modification
Modification
Weight reduction

Approximate SBP Reduction

(range)
5-20 mmHg/ 10 kg weight loss

Adopt DASH eating plan

8-14 mmHg

Dietary sodium reduction

2-8 mmHg

Physical activity
Moderation of alcohol
consumption

4-9 mmHg
2-4 mmHg
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

Impact of a 5 mmHg
Reduction

Overall Reduction

Stroke

14%

Coronary Heart Disease

9%

All Cause Mortality

7%
Hypertension 2003;289:2560-2572.

Reducing your weight by just 10 pounds may be enough to lower your

blood pressure. Losing weight can help to enhance the effects of high
blood pressure medication and may also reduce other risk factors, such as
diabetes and high bad cholesterol.

Thiazide
Diuretics
Mechanism: inhibit Na/K pumps in the
distal tubule
Examples:

Hydrocholorthiazide 12.5-25 mg
daily
Chlorthalidone 12.5-50 mg daily
Effective first line agent and provides
synergistic benefit
As single agent more effective if CrCl
>30 ml/min
Compelling indications: HF, High CAD
risk, Diabetes, Stroke, ISH

Aldosterone
Receptor
Antagonists
Mechanism: inhibit aldosterones
effect at the receptor, reducing Na
and water retention
Examples:

Spironolactone 25 mg daily
Can provide as much as 25
mmHg BP reduction on top of 4
drug regimen in resistant
hypertension
Monitor SCr and K
Compelling indications: HF

Nitrates
Mechanism: Direct
venodilation by release of
nitric oxide
Examples:

Isosorbide dinitrate 10
mg TID
IMDUR 30 mg daily

ACEI & ARBs

Mechanism: Inhibit vasoconstriction
by inhibiting synthesis or blocking
action of angiotensin II; provides
balanced vasdilation
Examples:

Enalapril 2.5-40 mg daily BID

Lisinopril 5 40 mg daily

In renal patients with

resistant hypertension
addition to 3-4 drug
regimen may help get
patient to goal

Monitor: SCr, K

Provide 8h nitrate free

interval daily

Compelling indications: HF, postMI, High CAD risk, Diabetes, CKD,

Irbesartan 150-300 mg daily

Losartan 25-100 mg Daily BID

Beta
Blockers
Mechanism: Competitively inhibit the
binding of catecholamines to betaadrenergic receptors
Examples:

Atenolol 25-100 mg PO daily

Diltiazem
and
Verapamil
Mechanism: Decrease calcium
influx into cells of vascular smooth
muscle and myocardium
Examples:

Diltiazem 60-480mg q6h to

daily

Metoprolol 25 -100 mg PO daily

or BID

Monitor: HR

Carvedilol 6.25-25 mg PO BID

Verapamil causes constipation

Monitor: HR, Blood Glucose in DM

Not contraindicated in asthma or
COPD but use caution
Compelling indications: HF, post-MI,
High CAD risk, Diabetes

Verapamil 60-480 q8h to daily

Relatively contraindicated in
heart failure
Compelling indications:
Diabetes, High CAD risk

Alpha2 Agonists:
Central Acting
Agents
Mechanism: false neurotransmitters
reduce sympathetic outflow reducing
sympathetic tone
Examples:

Dihydropyridine
Calcium
Channel
Mechanism: Blockers
Decrease calcium influx
into cells of vascular smooth muscle
Examples:

Clonidine 0.1-0.6 mg PO BID-TID;

patch

Amlodipine 2.5-10 mg PO daily

Methyldopa, Guanabenz,
Guanfacine

Do not use immediate release

nifedipine

Monitor: HR
Side effects often limiting: Dry mouth,
orthostasis, sedation
Clonidine patch can be useful in
elderly patients with labile blood
pressure

Felodipine2.5-10 mg PO daily

Monitor: Peripheral edema, HR

(can cause reflex tachycardia)
Good add on agent if cost is not an
issue

Vasodilators
Alpha1 Blockers
Mechanism: Inhibit peripheral postsynaptic alpha1 receptors causing
vasodilation
Examples:

Terazosin 1 20 mg daily
Doxazosin 1 16 mg daily

Mechanism: Direct vasodilation of

arterioles via increased intracellular
cAMP
Examples:

Hydralazine 20-400 mg BIDQID

Minoxidil 2.5-40 mg PO dailyBID

Cause marked orthostatic

hypotension, give dose at bedtime

Monitor: HR (can cause reflex

tachycardia), Na/Water retention

Consider only as add on therapy

Hydralazine is an alternative in
HF if ACEI contraindicated

Can be beneficial in patients with

BPH

Consider minoxidil in refractory

patients on multi-drug regimens

ACEI & ARBs

Mechanism: Inhibit vasoconstriction by inhibiting synthesis or
blocking action of angiotensin II; provides balanced vasdilation
Examples:

Enalapril 2.5-40 mg daily BID

Lisinopril 5 40 mg daily
Irbesartan 150-300 mg daily
Losartan 25-100 mg Daily - BID
Monitor: SCr, K
Compelling indications: HF, post-MI, High CAD risk, Diabetes,
CKD, Stroke

Pharmacologic Sites of
Action
Veins

Thiazides
Loops
Aldosterone Ant.
Nitrates
ACEI
ARB

Heart

Beta Blockers
Diltiazem
Verapamil
Via Central
Mechanism:
Clonidine

Arteries

Dihydropyridine
CCBs
Hydralazine
Minoxidil
Alpha1 Blockers
ACEI
ARB

Kondisi klinis yang mempengaruhi pemilihan obat antihipertensi

Penyakit
Penyakit
kardiovaskuler
Angina

Efek menguntungkan

Efek tidak
menguntungkan

Efek membahayakan

adenoreceptor bloker
CaCB

Gagal jantung

Diuretik

CaCB

adenoreceptor bloker

ACE inhibitor
Penyumbatan jantung

adenoreceptor bloker
Verapamil

Takikardia

adenoreceptor bloker CaCB

verapamil

Serangan jantung
Raynauds
phenomenon

Prazosin

adenoreceptor bloker adenoreceptor bloker

tanpa ISA
dengan ISA
CaCB
Non selektif
adenoreceptor bloker
Klonidin

Penyakit Respiratori
Asma
Penyakit penyumbatan
aliran udara kronis

adenoreceptor bloker
adenoreceptor bloker

Kondisi klinis yang mempengaruhi pemilihan obat antihipertensi (lanjutan)

Penyakit

Efek menguntungkan

Efek tidak
menguntungkan

Efek membahayakan

Penyakit metabolic
IDDM

Nonselektif
adenoreceptor bloker

NIDDM

Thiazid

Gout

Thiazid

Hiperlipidemia

adenoreceptor bloker Thiazid

Nonselektif
adenoreceptor bloker
Hidralazin

Kerusakan hati

CaCB
Penyakit
Genitourinari
Prostatism

adenoreceptor bloker Diuretic

Kerusakan ginjal

ACE inhibitor
Metildopa

CNS
Migrain
Depresi

Nonselektif
adenoreceptor bloker
Propranolol
Klonidin

Metildopa

eraksi umum obat dengan antiheipertensi

Kelas obat
antihipertensi
Thiazid diuretik

adrenoreceptor bloker

ACE inhibitor

Obat lain

Interaksi

NSAIDs

Menurunkan efek hipotensi

Digoksin

Toksisitas digoksin jika terjadi hipokalemia

Antiarrhythmics

Meningkatkan toksisitas dari amiodaron, disopyramide,

flecainide dan quinine jika hipokalemia terjadi. Aksi dari
lignokain, meksiletine dan tokainide antagonis oleh
hipokalemia

Lithium

Meningkatkan level lithium

Korticosteroid

Meningkatkan resiko hipokalemia

Anastetik

Meningkatkan efek hipotensi

Antiaritmia

Bradikardia, meningkatkan resiko toksisitas lignocain dengan

propranolol

NSAIDs

Hiperkalemia

Anastetik

Meningkatkan efek hipotensi

Lithium

Meningkatkan level lithium

Suplemen kalium

Hiperkalemia

Diuretik hemat
kalium

Hiperkalemia

raksi umum obat dengan antiheipertensi lanjutan

Angiotensin II reseptor bloker

Suplemen kalsium

Hiperkalemia

Diuretik hemat kalium

Hiperkalemia

adenoreceptor bloker

Diuretik and adenoreceptor

bloker
Kortikosteroid

Meningkatkan resiko hipotensi

pada dosis pertama
Menurunkan efek hipotensi

Prazosin

Indometasin

Menurunkan efek hipotensi

CaCB

Digoksin

Levodopa

Level digoksin meningkat

dengan diltiazem, nikardipin,
dan verapamil
Efek karbamazepin menjadi
lebih besar dengan diltiazem
dan verapamil
Efek isradipin, nikardipin, dan
nifedipin menurun oleh
primidon karbamezepin,
fenitoin dan phenobarbiton
Menurunkan efek hipotensi
yang bisa mengakibatkan krisis
hipertensi
Potensial hipotensi

Lithium

Meningkatkan level lithium

Nitrat

Meningkatkan efek hipotensi

Antiepilepsi

Metildopa

Antidepresan monoamine
oksidase inhibitor

Case Studies 1
A 55 yo west Indian women with
NIDDM, controlled by metformin, is
found on a visit to the clinic to have a
BP of 172/100 mmHg
Question:
1. Should drug therapy be initiated to
control her hypertension?
2. What antihypertensive drugs should
be avoided?

Answers case 1
1. First it is necessary to establish that the BP
reading is correct and consistent over at least
three separate occasions. The fact that her
NIDDM is controlled by metformin suggests she
may have a problem with weight control. It may
be important, therefore, to make sure that the
appropriate-sized cuff was used when her BP
was measure
2. Althought thiazid diuretics are effective
antihypertensive agent, they should be avoided
in diabetic patients because they reduce glucosa
tolerance. This is particularly important in
patient with NIDDM because of their effects on

Case studies 2
A 58 yo hypertensive female has
suffered side effects from a variety of
antihypertensive drugs. She is now
well controlled on enalapril, 20 mg
daily, but complains of a dry cough.
Her serum potassium level has also
risen.
Question: Should her treatment be
changed?

Answer case 2
The dry cough is a side effect of all ACE inhibitor (up
to 20% of patients, particularly middle aged
women, suffer this) but dose not necessary
require that the treatment should be stopped. It
appears to be an adverse effect of all ACE
inhibitors, so changing to an angiotensin II
receptor antagonist should provide similar control
of the BP without the same range of side effect, in
particular the cough. The rise in the serum
potassium level is potentially more serious, and a
possible explanation, such as concurrent therapy
with a potassium-sparing agent, must be explored
before changing to an alternative such as

Case 3: Diagnosis
AB is a 56 yo female with no
significant PMH. Her BMI is 26 kg/m2
and she has a family history positive
for Type 2 Diabetes. Her BP measured
on two consecutive clinic visits is
132/84. What is ABs BP classification?
1.
2.
3.
4.

Normal
Prehypertensive
Stage 1 Hypertension
Stage 2 Hypertension

Case 3: Therapy
What therapy should be initiated for
AB?
1.
2.
3.
4.

Enalapril 5 mg PO daily
Hydrochlorothiazide 25 mg PO daily
No therapy is indicated
Lifestyle modifications including weight
loss and DASH eating plan should be
encouraged

Case 3: Goal of Therapy

What is the goal of lifestyle modification
in AB?
1. Goal BP < 140/90, the goal is to get to
goal
2. Goal BP < 130/80, the goal is to get to
goal
3. Improve patients quality of life
4. Prevent onset of hypertension

Case 3: 3 years later

AB, now 59, returns to clinic with
marginal success at lifestyle changes.
Her BP has repeatedly measured
around 146/92. What is ABs BP
classification?
1.
2.
3.
4.

Normal
Prehypertensive
Stage 1 Hypertension
Stage 2 Hypertension

Case 1: 3 years
later
AB, now 59, returns to clinic with

marginal success at lifestyle changes.

Her BP has repeatedly measured
around 146/92. What should be done?
1.
2.
3.
4.

Enalapril 5 mg PO daily
Hydrochlorothiazide 25 mg PO daily
No therapy is indicated
Reinforce lifestyle modifications
including weight loss and the DASH
eating plan.

Case 4: Goal of Therapy

CD is a 50 yo black male with diet controlled
type 2 diabetes. Consecutive BP
measurements during recent clinic visits are
162/98 and 158/96. He is diagnosed with
Stage 2 Hypertension. What is the goal of
therapy for CD?
1. Goal BP <140/90
2. Goal BP <130/80
3. Slow the progression of diabetic renal disease
by reducing BP to <125/80
4. Improve patients quality of life

Case 4: Therapy
What therapy should be initiated for
CD?
1. A 6 month trial of lifestyle changes
should be initiated immediately
2. Hydrochlorothiazide 25 mg PO daily
3. Enalapril 10 mg PO daily
4. Enalapril / Hydrochlorothiazide 5/12.5
mg PO daily

Case 4: 5 years later cont.

He brings you his home BP log; Daily
readings over the last week are:
140/80, 128/74, 132/80, 156/88,
160/90, 130/82, 125/74.
What is the best course of action for
CD?
1. Reinforce lifestyle changes
2. Add atenolol 50 mg PO daily
3. Increase hydrochlorothiazide to 50
mg PO daily