Hipertensi Utk Awam
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Hipertensi dan Masalah disekitarnya
Lukman Muliadi
Apakah itu Hipertensi?
• Hipertensi atau Tekanan Darah Tinggi adalah suatu keadaan dimana tekanan darah di atas normal (>140 mmHg untuk sistolik dan >90 mmHg untuk diastolik)
• Hipertensi bisa menyerang anak-anak atau orang dewasa, namun umumnya pada orang dewasa di atas 35 tahun
BP CLASSIFICATIONESH-ESC & WHO-ISH 2003 BP Classification
Systolic BP Diastolic BP JNC VII
Bp Classification
Optimal <120 / <80 <120/<80 Normal
Normal 120-129 / 80-84 120-129 /80-84 Prehypertension
High normal 130-139 / 85-89 130-139 / 85-89
Grade 1 Hypertension (mild)
140-159 / 90-99 140-159 / 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 Hypertension
Isolated Systolic Hypertension> 140 < 90
Hypertension SyndromeHypertension SyndromeIt’s More Than Just Blood PressureIt’s More Than Just Blood Pressure(Tidak hanya tekanan darah yang meningkat)(Tidak hanya tekanan darah yang meningkat)
DecreasedArterial
Compliance Endothelial Dysfunction
Abnormal Glucose
Metabolism
Neurohormonal Dysfunction
Renal-Function Changes
Blood-Clotting Mechanism
Changes
Obesity
Abnormal Insulin
Metabolism
LV Hypertrophyand Dysfunction
Accelerated Atherogenesis
Abnormal Lipid Metabolism
Hypertension
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.
The Metabolic Syndrome :
The Iceberg Concept
Hypertension Linked To Chronic Renal Disease Among 332,544 Men Screened
for MRFIT
0
50
100
150
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250
<8080-84
85-8990-99
100-109110
180 160-179 140-159 130-139 120-129 <120
Systolic BP (mm Hg) Diastolic BP (m
m Hg)
Adapted from Klag MJ, et al. N Engl J Med. 1996;334(1):13-18.© Massachusetts Medical Society
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0Age
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Apa Penyebab Hipertensi ?
• 90-95% hipertensi tidak diketahui penyebabnya
• 5-10% disebabkan penyakit lain :– Gangguan ginjal– Gangguan pembuluh darah– Ganguan hormonal: hypertiroidi
• - obat obatan : NSAID,Steroid, kontrasepsi hormonal
hipertensi(patogenesis)
TEKANAN DARAH = CURAH JANTUNG x RESAISTENSI PERIFERA
Hipertensi Peningkatan CJ Peningkatan RP
Preload Kontraktilitas Konstriksi Fungsional Hipertrofi struktural
Volume Redistribusi
Cairan Cairan
Retensi Luas hiperaktif RAS Gangguan Hiper
Na Ginjal Filtrasi S.Simpatis membran sel insulinemi
Asupan Na Gg Stress Gg
ekses genetik Genetik Obesitas EDF
HEREDITER - LINGKUNGANUmur
0 – 30 tahunPRE-HIPERTENSI
Normotensi HIPERTENSI DINI 20 – 40 tahun
HIPERTENSI (KLINIS) 30 –50 tahun
TANPA KOMPLIKASI DENGAN KOMPLIKASI
Hipertensi Jantung P.Darah Besar Otak GinjalMaligne Hipertrofi Aneurisma Iskemia Sklerosis
Gagal Diseksi Trombosis Gagal GinjalInfark Perdarahan
Gambar 1. Perkembangan alamiah hipertensi esential tanpa terapi
Perkembangan alamiah hipertensi esential tanpa terapi
Blood Pressure rises with age
0
10
20
30
40
50
60
70
%
18-29 30-39 40-49 50-59 60-69 70-79 80+
0
10
20
30
40
50
60
70
%
18-29 30-39 40-49 50-59 60-69 70-79 80+
Kannel-W. Cardioprotection and Antihypertensive Therapy, Am. J. Cardiol 1996 ; 77
In the elderly, one out of two is hypertension
Prevalence of Hypertension by age in USA
Age Group
Levels of Risk Associated with Smoking, Hypertension and Hypercholesterolaemia
Levels of Risk Associated with Smoking, Hypertension and Hypercholesterolaemia
.x1,6 x4
x3
x6
x16
x4.5 x9
Hypertension(SBP 195 mmHg)
Serum cholesterol level(8.5 mmol/L, 330 mg/dL)
Smoking
Poulter N et al., 1993
Systolic BP is a better indicator of CAD Systolic BP is a better indicator of CAD risk than diastolic blood pressure (DBP)risk than diastolic blood pressure (DBP)
0
10
20
30
40
50
60
70
80
90
100
MRFIT*: CAD death and BPMRFIT*: CAD death and BP
BP 130 150 170 190 210 DBP 80 90 100 110 120
DBP
Systolic BP
Ag
e-a
dju
ste
d C
AD
dea
th r
ate
per
10
,00
0 p
erso
n-y
ear
s
*Multiple Risk Factor Intervention Trial.
Adapted from Neaton et al, Arch Intern Med, 1992.
Systolic
mm Hg
BP directly correlates with risk of strokeBP 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
ati
ve
risk
of
stro
ke
MRFIT: elevated systolic BP MRFIT: elevated systolic BP confers increased risk of strokeconfers increased risk of stroke
mm Hg
0
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2
3
4
5
6
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9
Systolic BPDBP
Systolic BP
DBP
Elevated systolic BP interacts with diabetesElevated systolic BP interacts with diabetesto increase CVD riskto increase CVD risk
MRFIT: men with diabetes and elevated systolic BP MRFIT: men with diabetes and elevated systolic BP are at greater risk of CVD than those without diabetesare at greater risk of CVD than those without diabetes
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250
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<120 120-139 140-159 160-179 180-199 ≥200
CV
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ea
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Systolic BP (mm Hg)
Patients with diabetes
Patients without diabetes
Stamler et al, Diabetes Care, 1993.
Importance of blood pressure control
“It is estimated that in patients with
stage 1 hypertension and additional
cardiovascular risk factors,
achieving a sustained 12-mmHg reduction
in SBP over 10 years will prevent 1 death
for every 11 patients treated.”
JNC VII 2003
Millimetres matter …
“For individuals 40-70 years of age, each
increment of 20 mmHg in systolic BP or
10 mmHg in diastolic BP doubles the risk
of CVD across the entire BP range from
115/75 to 185/115 mmHg”
JNC VII. JAMA 2003;289:2560-2572BP, blood pressure; CVD, cardiovascular diseaseBP, blood pressure; CVD, cardiovascular disease
Millimetres matter …
“A 2-mmHg reduction in DBP would
result in … a 6% reduction in the risk
of
CHD and a 15% reduction in the risk of
stroke and TIAs”Cook NR, et al. Arch Intern Med 1995;155:701-709
DBP, diastolic blood pressure; CHD, coronary heart DBP, diastolic blood pressure; CHD, coronary heart disease; disease; TIA, transient ischaemic attackTIA, transient ischaemic attack
Relative importance of SBP and DBP as predictors of CHD risk as a function of age
* The difference between SBP and DBP proportional hazard regression coefficients, ie, (SBP) - (DBP), was estimated for each age group
SBP, systolic blood pressure; DBP, diastolic blood pressure;CHD, coronary heart disease
25 6545 5535 75
(SBP) -
(DBP)*
Age (years)
Favours DBP
Favours SBP
-1.0
-0.5
0.0
0.5
1.0
-1.5
p=0.008
Franklin SS, et al. Circulation 2001;103:1245-1249
Natural history of coronary heart disease
Atherosclerosis
Risk factor :• Hypertension• Hyperlipidemia• Diabetes• Insulin resistance
LV Hypertrophy
Coronary Artery Disease
Myocardial Ischemia
MyocardialInfarction
Remodelling
VentricularDilatation
Heart Failure
Death
Arrhythmia
SuddenDeath
Dzau & Braunwald, 1991
Vessel
Kidney
Hypertension
Left Ventricular Hypertrophy
Chronic Heart Failure
Myocardial Infarction
Congestive Heart Disease
ArrhythmiaArteriosclerosis
Peripheral Vascular Disease
Coronary Heart Disease
Renal Insufficiency
ESRD / Gagal Gnjal
Heart Brain
Stroke
The pioneersThe pioneersVasodilation treatment with fever-Vasodilation treatment with fever-
producing or antimalarial agents :producing or antimalarial agents :►Fries 1940s:Fries 1940s:
This was the first time we had seen reversal This was the first time we had seen reversal of the signs of malignant hypertension of the signs of malignant hypertension following an anti-hypertensive drug. It was following an anti-hypertensive drug. It was an exciting experiencean exciting experience
► Page 1949 :Page 1949 : I need hardly say this an unpleasant I need hardly say this an unpleasant
treatment butconsidering the danger of the treatment butconsidering the danger of the diseaseto the life of the patient it is a small diseaseto the life of the patient it is a small price to pay for the benefits price to pay for the benefits
A case of untreated A case of untreated hypertensionhypertension
YearYear Blood Blood pressurepressure
ComplicationComplicationss
TreatmentTreatment
19351935 136/78 (age 53)136/78 (age 53)
19371937 162/98162/98 PhenobarbitalPhenobarbital
1937-1937-19411941
170-180/90-100170-180/90-100 Low salt and low fat Low salt and low fat diet/massages/digitalidiet/massages/digitaliss
19411941 188/105188/105 Cardiac Cardiac enlargement enlargement Probable lacunnar Probable lacunnar infarctsinfarcts
19441944
1944-1944-19451945
186/108186/108
180-230/110-126180-230/110-126CHFCHF
Renal failureRenal failure
April12, April12, 19451945
Cerebral Cerebral haemorrhage-haemorrhage-death, age 63death, age 63
Pengukuran Tekanan Darah Contoh tekanan darah Normal : 120/80 mmHg
Tinggi : >140/>90 mmHg
Pengukuran Tekanan Darah
• Ada 2 angka yang terukur dalam pengukurang tekanan darah :– Sistolik (tekanan ketika jantung memompa)– Diastolik (tekanan ketika jantung menerima
darah kembali)
Sistolik (tekanan yang lebih tinggi) saat ini dianggap LEBIH BERPERAN dalam menyebabkan komplikasi: PJK, stroke dan gagal ginjal
Tehnik Pengukuran Tekanan Darah
1. Pasien harus tenang / relaks, tangan ditopang, lengan baju longgar
2. Sebaiknya ½ jam setelah makan / merokok3. “Cuff” sesuai lingkar lengan4. Manometer harus tegak lurus. Air raksa
dipompa sampai denjut hilang, diturunkan pelahan : 2-3 mm/detik.
5. Bunyi pertama = TDS, bunyi hilang = TDD 6. Hipertensi ringan diulang setelah 1 minggu
Perubahan Tekanan Darah Terkait Aktivitas
Aktivitas TDS(mmHg) TDD(mmHg)Rapat
Bekerja
Jalan
Berpakaian
Telepon
Makan
Kerja tulis menulis
Membaca
Nonton TV
Relaks
Tidur
+20.2
+16.0
+12.0
+11.5
+9.5
+8.8
+5.9
+1.9
+0.3
0.0
-10.0
+15.0
+13.0
+9.2
+5.5
+7.2+9.6
+5.3
+2.2
+1.1
0.0
-7.6
Faktor Risiko Hipertensi
• Tidak dapat dimodifikasi– Usia lanjut– Keturunan
• Dapat dimodifikasi– Kegemukan– Asupan garam berlebih– Kurang bergerak/beraktivitas– Stress– Merokok
Proof of BenefitProof of Benefit► 1960s to 1980s several major clinical trials establish the facts 1960s to 1980s several major clinical trials establish the facts
that early treatment of hypertension would prevent that early treatment of hypertension would prevent complication and prolong lifecomplication and prolong life VAS, USPHS, HDFPVAS, USPHS, HDFP
► Benefits of therapy :Benefits of therapy :ComplicationsComplications ControlControl
No. No. %%
TreatedTreated
No. No. %%
% Improvement% Improvement
Total morbid eventsTotal morbid events 563 563 9.09.0
417 417 6.66.6
2727
Total mortalityTotal mortality 342 342 5.45.4
252 252 4.14.1
2424
Cerebrovascular events ; Cerebrovascular events ; fatal & nonfatal fatal & nonfatal
140 140 2.22.2
76 76 1.21.2
5050
Fatal coronary eventsFatal coronary events 79 79 1.21.2
46 46 0.70.7
4242
Data from a subset of patients in VACS, USPHCS, HDFP, AustS, Oslo Study
Relative risk reduction of fatal events and combined fatal and non-fatal events in patients on active treatment versus placebo or no
treatment
S-D hypertension
Risk reduction
P
SIS-hypertension
Risk reduction
P Mortality
all cause
cardiovascular
noncardiovascular
-14% <0.01
-21% <0.001
-1% ns
-13% <0.02
-18% <0.01
-1% ns
Fatal and non fatal events
stroke
coronary
- 42% <0.001
- 14% <0.01
- 30% <0.001
- 23% <0.001
ESH-ESC 2003
BP Control RatesTrends in awareness, treatment, and control of high
blood pressure in adults ages 18–74
National Health and Nutrition Examination Survey, Percent
II1976–80
II(Phase 1)1988–91
II(Phase 2)1991–94 1999–2000
Awareness 51 73 68 70
Treatment 31 55 54 59
Control 10 29 27 34
Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC6.
27 % 22% 20,5% 20% 19%
6 % 24% 22,5% 17,5% 9%
< 140 / 90 mmHg < 160 / 95 mmHg USA Canada Finland Spain Australia
England France Germany Scotland India
> 65 yr only
European heart journal suppl B vol 2 ,March 2000
% Patients with controlled BP world-wide% Patients with controlled BP world-wide
Goals of treatment
JNC VII ( 2003 ) : @ < 140 / 90 mmHg or < 130 / 80 mmHg for those with Diabetes or Chronic Kidney disease. @ Achieve SBP goal especially in persons >50 years of age.
ESH ( 2003 ) : @ At least below 140 / 90 mmHg ( lower values if tolerated )@ Below 130 / 80 mmHg in Diabetics.@ Keeping in mind, however, that systolic below 140 mmHg
may be difficult to achieved in elderly( more flexible )
BP Threshold & Target BP (mmHg)
Low and medium risk >140/90 <140/90
High risk <160/90 <140/90
DM <130/<80
Goals BP
JNC 7 - WHO/ISH –ESH-ESC, 2003
AASK MAP <92
Target BP (mmHg)
Multiple antihypertensive agents are needed to achieve target BP
Number of antihypertensive agents1
UKPDS DBP <85
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
Trial 2 3 4
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure
IDNT SBP <135/DBP <85
ALLHAT SBP <140/DBP <90
Bakris GL, et al. Am J Kidney Dis 2000;36:646-661;Lewis EJ, et al. N Engl J Med 2001;345:851-860;
Cushman WC, et al. J Clin Hypertens 2002;4:393-404
Choose between
Low-dose 2-drug combinationLow-dose single agent
Not at BP goal
Full dose ofsingle agent
Switch todifferent agent
at low dose
Full dose of2-drug
combination
Add athird drugat low dose
Not at BP goal
2–3 drugcombinationat full dose
Full doses of 2–3-drugcombination
ESH–ESC: Algorithm for ESH–ESC: Algorithm for Treatment of HypertensionTreatment of Hypertension
Full-dosesingle agent
TOD = target organ damage
Marked BP elevation
High/very high CV risk
Lower BP target
Mild BP elevation
Low/moderate CV risk
Conventional BP target
Task Force for ESH–ESC. J Hypertens 2007;25:1105–87
Updated UK NICE Guidelines for the Treatment of Newly Updated UK NICE Guidelines for the Treatment of Newly Diagnosed HypertensionDiagnosed Hypertension
ACEI (or ARB*) + CCB orACEI (or ARB*) + thiazide diuretic
<55 years
ACEI (or ARB*) + CCB + diuretic
CCB or thiazide-type diuretic
ACEI (or ARB*)
55 years or black patients at any age
Add further diuretic therapy, α-blocker, or β-blocker.Consider seeking specialist advice
Step 1
Step 2
Step 3
Step 4
Management of Hypertension (JNC VII)
BP Classification
Lifestyle modification
Initial Drug
(-) compelling Indication
Therapy
(+) compelling indication
Normal Encourage
Pre-
Hypertension
Yes No AHD indicated AHD (s) for the compel- ling indications
Stage 1
Hypertension
Yes Thiazide-type D for most, may consider other AHD.
AHD(s) for the compel- ling indications.
Other AHD as needed.
Stage 2
Hypertenssion
Yes 2-AHDs combination for most (usually thiazide-type D and ACEI or ARB or BB or CCB
AHD(s) for the compel- ling indications.
Other AHDs (D.ACEI,ARB,BB.CCB)
Modified from JNC VII
Treatment initiation: ESH/ESC 2003Blood pressure
Other risk factors and disease history
Normal High normal Grade 1 Grade 2 Grade 3
No other risk factors
No BP intervention
No BP intervention
Lifestyle changes for several months, then drug treatment if preferred by the patient and resources available
Lifestyle changes for several months, then drug treatment
Immediate drug treatment and lifestyle changes
1-2 risk factors Lifestyle changes
Lifestyle changes
Lifestyle changes for several months, then drug treatment
Lifestyle changes for several months, then drug treatment
Immediate drug treatment and lifestyle changes
3 or more risk factors, target organ damage, or diabetes
Lifestyle changes
Drug treatment and lifestyle changes
Drug treatment and lifestyle changes
Drug treatment and lifestyle changes
Immediate drug treatment and lifestyle changes
Associated clinical conditions
Drug treatment and lifestyle changes
Immediate drug treatment and lifestyle changes
Immediate drug treatment and lifestyle changes
Immediate drug treatment and lifestyle changes
Immediate drug treatment and lifestyle changes
ESH/ESC Guidelines 2003. J Hypertens 2003;21:1011-1053
Diuretics
Angiotensinreceptor blockers
(ARBs)
Calcium channelblockers (CCBs)
Angiotensin-converting enzyme (ACE) inhibitors
-blockers
-blockers
Available as a single-pill combination
Less frequently used/combination used as necessary
Task Force for ESH–ESC. J Hypertens 2007;25:1105–87
ESHESC Recommendations for Combining BP-loweringDrugs and Availability as Single-pill Combinations
Mitos-mitos di seputar Hipertensi
• Tekanan darah diastolik (angka yang lebih rendah) lebih penting dari sistolik– FAKTA:
• Tekanan darah sistolik dan diastolik sama-sama penting, bahkan pada usia lanjut, tekanan darah sistolik lebih harus dikontrol
Mitos-mitos di seputar Hipertensi
• Pada orang tua, sudah biasa tekanan darahnya tinggi, sehingga tidak perlu diobati (100 + umur mmHg adalah wajar)– FAKTA:
• Baik orang muda maupun orang tua, tekanan darah HARUS di bawah 140/90 mmHg untuk mencegah komplikasi
Mitos-mitos di seputar Hipertensi
• Jika saya minum obat hipertensi dan tekanan darah saya terkontrol baik, obat tersebut tidak perlu diminum lagi– FAKTA:
• Tekanan darah terkontrol tsb. karena disebabkan oleh obat. Jika obat dihentikan maka tensi akan meningkat kembali. Hipertensi tidak dapat disembuhkan, hanya dapat dikendalikan. Jadi obat hipertensi harus terus diminum sesuai instruksi dokter
Mitos-mitos di seputar Hipertensi
• Jika kita pusing-pusing dan leher terasa kaku, itu berarti tensi kita sedang naik. Jika tidak terasa apa-apa, tensi kita normal– FAKTA:
• Hipertensi itu penyakit yang umumnya tidak bergejala. Untuk mengetahui apakah tensi kita naik atau tidak hanyalah mengukur dengan tensi meter. Periksalah tekanan darah secara teratur untuk mengetahui berapa tekanan darah kita.
• Sebagian besar hipertensi TIDAK bergejala• Tekanan darah tinggi bisa merusak organ-
organ tubuh yang berhubungan erat dengan pembuluh darah
• Hipertensi adalah penyebab utama STROKE, SERANGAN JANTUNG DAN GAGAL GINJAL
• Hipertensi dapat dikontrol untuk mencegah komplikasi tersebut
Hipertensi = “Silent Killer”
Don’t wait to treat hypertensionDon’t wait to treat hypertension““Awaiting overt signs and symptoms of Awaiting overt signs and symptoms of
coronary disease before treatment is coronary disease before treatment is no longer justified.”no longer justified.”
““In some respects, the occurrence of In some respects, the occurrence of symptoms may be regarded more symptoms may be regarded more properly as a medical failure than as properly as a medical failure than as the initial indication for treatment.”the initial indication for treatment.”
William B. Kannel, MDWilliam B. Kannel, MD
Department of MedicineDepartment of Medicine
Boston University Medical Boston University Medical CenterCenter
Kannel, Atherosclerosis and Coronary Artery Disease, 1996.
““Menunnggu sampai gejala dan tanda Menunnggu sampai gejala dan tanda penyakit jantung koroner timbul baru penyakit jantung koroner timbul baru diberi terapi sudah tidak benar .”diberi terapi sudah tidak benar .”
““Pada beberapa keadaan, timbulnya atau Pada beberapa keadaan, timbulnya atau telah adanya gejala justru telah adanya gejala justru menggambarkan kegagalan tindakan menggambarkan kegagalan tindakan medis, bukan saat baru mulai terapi.”medis, bukan saat baru mulai terapi.”
——William B. Kannel, MDWilliam B. Kannel, MD
Department of Medicine Department of Medicine
Boston University Medical Center Boston University Medical Center
10 kewajiban penderita hipertensi
1. Mengukur tekanan darah secara teratur
2. Jangan lupa mengkonsumsi obat sesuai aturan dokter
3. Mengontrol berat badan
4. Tidak mengkonsumsi garam berlebih (menghindari makanan bergaram tinggi)
5. Makan makanan rendah lemak
6. Berhenti merokok
7. Berkonsultasi dengan dokter secara teratur
8. Latihan fisik sesuai anjuran dokter
9. Menjalani kehidupan secara normal dan sehat
10. Menganjurkan keluarga (orang tua, kakak, adik, paman, anak dll) untuk memeriksakan tekanan darah secara teratur (risiko keturunan)
Obat-obat yang ideal
• Efektif menurunkan tekanan darah• Efek samping minimal• Diminum sekali sehari• Efek penurunan tekanan gradual• Memiliki “drug holiday protection” (melindungi
pasien yang lupa minum obat)• Tidak perlu memilih obat yang penurunan
tekanan darahnya cepat (kecuali kasus emergency)
Tips untuk mengurangi berat badan
• Kurangi makanan yang digoreng• Kurangi mentega, minyak dan lemak• Kurangi porsi makanan• Kurangi daging dan pilihlah ayam atau ikan
(kulit ayam disingkirkan)• Konsumsi buah dan sayuran lebih banyak• Konsumsi susu yang rendah lemak• Aktivitas fisik 30-60 menit 3-6 kali seminggu
Tips untuk mengurangi asupan garam
• Kurangi jumlah garam dalam masakan• Tambahkan bumbu dan penyedap untuk mengimbangi
rasa masakan• Kurangi kripik kentang dan jagung asin, hot dogs,
ikan asin, burger yang banyak mengandung garam• Tambahkan konsumsi buah dan sayur segar dan
bukan kalengan• Perhatikan LABEL kandungan garam dalam makanan
Obat-obat anti-hipertensi
• Bersikap sabar dalam menjalani pengobatan, tidak mengharapkan terapi yang “ajaib” yang cepat menurunkan tekanan darah
• Memberi kesempatan pada tubuh untuk menyesuaikan dengan obat yang mungkin memerlukan waktu untuk mengendalikan tekanan darah
• Obat diminum sesuai dengan anjuran dokter. Tidak menghentikan pengobatan sendiri atau merubah dosis dan segera mengunjungi dokter jika ditemukan adanya efek samping
Obat-obat anti-hipertensi
• Diuretik
• Beta bloker
• Antagonis kalsium
• ACE inhibitor
• Alfa bloker
• Angiotensin II antagonis
• Central agonist dan vasodilator
• Anti Renin
Development of Antihypertensive Development of Antihypertensive TherapiesTherapies
Directvasodilators
Alphablockers
Renin Inh
Peripheralsympatholytics
Ganglion blockers
Veratrumalkaloids
Central alpha2 agonists
Non-DHPCCBs
Beta blockers
Thiazidediuretics
DHP CCBs
ARBsACEinhibitors
Effectiveness
Tolerability
1940s 1950 1957 1960s 1970s 1980s 1990s 2005+
DHP, dihydropyridine; CCB, calcium channel blocker; ARB, angiotensin II receptor blocker.
The primary goal of treatment is to achieve maximum reduction in total
CV risk, through treatment of elevated BP and all associated
reversible risk factors ESH/ESC 2007
AMLODIPINE
• Obat yang mempunyai masa kerja panjang dari generasi kedua antagonis kalsium
• Mempunyai waktu paruh 35-48 jam
• T/P Ratio >50%
• Dosis sekali sehari
• Menurunkan tekanan darah secara gradual
• Olmesartan medoxomil is a prodrug, which is hydrolyzed to its active metabolite, olmesartan
• Absolute bioavailability 25.6%
• Time to Cmax ~2 hours
• t1/2 ~10-15 hours
• Dual elimination: – 40% renal
– 60% hepatobiliary
Schwocho LR, et al. J Clin Pharmacol 2001;41:515-527;Laeis P, et al. J Hypertens 2001;19(Suppl 1):S21-S32
Pharmacokinetics: Olmesartan
• Not metabolized by cytochrome P450 system; interactions with drugs metabolized by CYP450 unlikely
• Can be administered with or without food
• No dosage adjustment necessary for the elderly or in patients with renal or hepatic impairment
– BUT not recommended for patients with severe renal or hepatic impairment
Schwocho LR, et al. J Clin Pharmacol 2001;41:515-527;Laeis P, et al. J Hypertens 2001;19(Suppl 1):S21-S32;
von Bergmann K, et al. J Hypertens 2001;19(Suppl 1):S33-S40
Pharmacokinetics: Summary (cont.)
Olmesartan may give more prolonged AT1 blockade than
irbesartan or valsartan
0
3.16
1.78
1.19
1.84
0
1
2
3
4
5
Placebo Olmesartan 40mg
Irbesartan 300mg
Valsartan 160mg
Valsartan 320mg
Chan
ge fr
om p
redo
se to
24
hour
s in
mea
n PRA
(ng/
mL/
h)
p vs placebo <0.0001 0.005 0.058 (NS) 0.004
p vs olmesartan 0.028 0.002 0.036
n=20
PRA, plasma renin activity
Jones M, et al. Presented at ASH 2006; Abstract P-195
-13.0
-8.9 -9.2
-10.8
-14
-12
-10
-8
-6
-4
-2
0
Ch
ange
in B
P (
mm
Hg)
Olmesartan 20 mg/d
Losartan50 mg/d
Valsartan 80 mg/d
Irbesartan150 mg/d
Oparil S, et al. J Clin Hypertens 2001;3:283-291
** **
*
n=588* p0.05** p0.005
Results at Week 2 (cont.) Change in SeSBP
SeSBP, seated systolic blood pressure;BP, blood pressure
-11.5
-8.2 -7.9
-9.9
-12
-8
-4
0
Ch
ange
in B
P (
mm
Hg)
Olmesartan 20 mg/d
Losartan50 mg/d
Valsartan 80 mg/d
Irbesartan150 mg/d
Oparil S, et al. J Clin Hypertens 2001;3:283-291;Brunner HR. J Hypertens 2003;21(Suppl 2):S43-S46
* p<0.05 ** p<0.0005
** **
*
n=588
Results at Week 8 Change in SeDBP
40% 46% 16%
SeDBP, seated diastolic blood pressure; BP, blood pressure
Compliance at 1 year withantihypertensive treatment
Bloom BS, et al. Bloom BS, et al. Clin TherClin Ther 1998;20:671-681 1998;20:671-681
3843
50
5864
0
10
20
30
40
50
60
70
Diuretics Beta- blockers CCBs ACE inhibitors ARBs
Com
plia
nce
at 1
ye
ar (
%)
** p<0.007 vs ACE inhibitors p<0.007 vs ACE inhibitors
**
ACE, angiotensin-converting enzyme; ACE, angiotensin-converting enzyme; CCB, calcium-channel blocker; ARB, angiotensin II receptor CCB, calcium-channel blocker; ARB, angiotensin II receptor blockerblocker
ACEI + CCB• Less peripheral oedema• Less cough• Potentiation of the BP lowering effect• Greater reduction of CV events• Greater organ protection• Antiinflamatory vasc effect• Anti atherogenic properties• Anti diabetogeniceffects• Neutral effects on lipid profile and uric acid
Take home messages
• Kenalilah tekanan darah anda
• Kendalikanlah dengan :– Mengkonsumsi obat sesuai anjuran dokter– Rajin berkonsultasi pada dokter– Mengurangi asupan garam– Mengendalikan berat badan– Berhenti merokok
- Olah raga teratur
Summary
• Regardless of the blood pressure level, all patients should adopt appropriate lifestyle modifications
• A low dose of a diuretic should be considered as the first choice of therapy for the majority of patients without a compelling indication for another class of drug
2003 WHO/ISH Statement on Hypertension. J Hypertens 2003;21:1983-1992
Summary• Specific drug classes may differ in their effects• Main benefits are due to BP lowering• Drugs are not equal in adverse-event profiles• Major drug classes are suitable for initiation and
maintenance of therapy• Choice of drug will be influenced by patient
experience and preference, and cost and risk profile
• Long-acting drugs that provide once-daily, 24-hour efficacy are preferable
ESH/ESC Guidelines 2003. J Hypertens 2003;21:1011-1053BP, blood pressure
Thank You