 ISH/WHO has agreed to adopt in

principle the definition and classification

provided in JNC-VI. New definition
defines the lower limits of hypertension as
140 mmHg SBP and 90 mmHg DBP

 Hypertension is therefore defined as a

SBP of 140 mmHg or greater and/or a
DBP of 90 mmHg or greater in a subject
who are not taking antihypertensive
medication.

WHO/ISH Guidelines

2
Chalmers J., et al. J. Hypertension. 1999 ; 17
ESH-ESC Tekanan Darah JNC VII
mHg
optimal < 120 / < 80 normal
normal 120-129 / 80-84 Pre-Hp
nl tinggi 130-139 / 85-89 Pre-Hp
Gr 1 (rng) 140-159 / 90-99 Hp st 1
Gr 2 (sdg) 160-179 / 160 / Hp st 2
100-109 100
Gr 3 (brt) >180/>110
ISH >140 / < 90 ISH
 Hypertension
And End-Organ Damage

Left ventricular Heart Failure Coronary heart

hypertrophy disease

Persistently elevated
blood pressure

PVD Stroke
End-stage renal
disease

5
 Treatment of Hypertension
Background
• Hypertension is the major risk factor for
coronary heart disease and congestive
heart failure
• Hypertension is second only to diabetes as
the cause of renal failure
• In a recent meta analysis, treating
hypertension reduced the incidence of
stroke by 38% and coronary heart disease
by 16%
 Goal of Hypertension Therapy

To achieve the maximum reduction in

the total risk of cardiovascular / target
vital organ morbidity and mortality

Target:
BP: SBP < 130 – 140 mm Hg
DBP < 90 mm Hg
JNC. VI, 1997 & WHO – ISH, 1999
 JNC VII  WHO-ISH
1. <140/90 pada hp 1. <140/90 pada
tanpa penyulit pasien lanjut usia
2. <130/85 pada DM 2. <135/90 pada hp
atau penyakit ginjal tanpa penyulit
3. <125/75 pada
insufisiensi ginjal
dan proteinuri
>1gr/24 jam
 Pilih antara

Obat tunggal Kombinasi 2

dosis rendah dosis rendah
Sasaran belum tercapai

Obat Ganti obat Kombinasi Tambah obat

sebelumnya lain dosis sebelumnya ketiga dosis
dosis penuh rendah dosis penuh rendah
Sasaran belum tercapai

Kombinasi 2-3 macam Kombinasi 2-3 macam

obat obat dengan dosis efektif
 JNC VII, 2003 ‘Prinsip Pengobatan Hipertensi yang ideal’

Modifikasi gaya hidup

Belum mencapai target < 140/90 mmHg

Pilihan obat inisial

Tanpa indikasi wajib Dengan indikasi wajib

HP Stage 1 HP Stage 2 Obat2an untuk indikasi

mono atau biasanya wajib dan/atau obat2an
kombinasi kombinasi AH lain

Belum mencapai target tekanan darah

Optimalkan dosis atau berikan obat tambahan sampai target tercapai

Pertimbangkan konsultasi spesialis
Algorithm for the Treatment of Hypertension
Begin or Continue Lifestyle Modifications

Not at Goal Blood Pressure (<140/ 90 mmHg)

Lower goals for patients with diabetes or renal disease

Initial Drug Choices

Diuretics , Beta-Blockers, Calcium Channel Blockers ( CCBs ), ACE Inhibitor & AIIRA

Not at Goal Blood Pressure

No response or troublesome side Inadequate response but well

effects tolerated

Substitute another drug from Add a second agent from a

a different class different class ( diuretic if not
already used )

Not at Goal Blood Pressure

Continue adding agents from other classes.

Consider referral to a hypertension specialist
 Results of therapy
Effect of antihypertensive drug treatment
on cardiovascular events
% reduction of events

-10
-16
-20 -21
-30
-35
-40 -38

-50 -52
-60
CHF Strokes LVH CVD death CHD
fatal/non events

Combined results of 17 randomized placebo controlled trial (48000 pts)

with diuretics or betablocker. Moser;AJCC;1996;27:1214-1218 12
WHO-ISH:
Target blood pressure:

 young and middle age <130/85mmHg

 elderly <140/90mmHg

13
 Recommendations for antihypertensive
treatment in elderly patients
3 consecutive measurements
Threshold BP
SBP DBP Target BP
mm Hg mm Hg mm Hg

WHO/ISH 1993 160 95 <140/90

Working group on 140 90 <140/90 or

hypertension in 20 mm Hg  in SBP
the elderly (USA)

Sweden 180 100 <160/90

14
Concomitant disorders are common in
hypertensive at age 70
CHD No hypertension
Angina (n=2338)
pectoris
Hypertension
Myocardial (n=755)
infarction
Stroke
Diabetes

Claudication
Obstructive
Lung disease
%

0 5 10 15 20 25 30 35 40 45
Landahl 1996
15
Venous function is reduced with age

Muscle strength Baroreceptor function

Venous tone Plasma volume

Valvular function

Hydrostatic capillary Postural hypotension

pressure

Peripheral edemas

16
Principles of management of hypertension
in the elderly

Therapeutics strategies: ISH = diastolic

hypertension

Start with lifestyle modifications

Avoid drugs that may worsen co-morbid condition or

induce orthostatic hypotension or cognitive
dysfunction

Low starting dose - usually half recommended in

younger patients

17
 Goal of therapy <140/90 mmHg
 Choice of anti-hypertensive agent depend
on the presence of concomitant
conditions
 First line: low dose diuretics
 Beta blocker is not the drug of choice,
except in angina or post AMI
 ACEI and calcium blocker if diuretics and
beta blocker contraindicated ( asthma,
diabetes )
18
 Diuretics B-blocker
 Cerebrovascular events 0.61 0.75
 Fatal strokes 0.67
 Coronary heart disease 0.74 1.01
 Cardiovascular death 0.75 0.98
 All causes mortality 0.86 1.05

Messerli: Jama1998:279:1903-1907
19
 Diabetes Mellitus, congestive HF,
ACEI
 Angina Pectoris, post MI
Betablocker
 Isolated systolic hypertension
Diuretic/Ca antagonist

21
 Ideal Antihypertensive Agent

EFFECTIVE - for systolic & diastolic hypertension

EASY TO USE – once a day

SAFE – free of brain, heart & kidney side effects

AFFORDABLE – economical daily cost

Int’l Forum on Angiotensin Receptor Antagonist, Monte Carlo, 19999

 Calcium Channel Blockers (CCBs)

 Dihydropyridine ( DHP )
Nifedipine, Amlodipine, Felodipine
 Non-Dihydropyridine ( NDHP )
Diltiazem, Verapamil

Opie, Drugs for the Heart, 2001

 Calcium Channel Blockers (CCBs)

Advantages
• Highly effective in reducing BP in the elderly
• Favorable or neutral effects on concomitant disease
• Symptomatic relief of angina pectoris
• No metabolic side-effects

Disadvantages
• Tachycardia
• AV block
• Constipation
• Ankle edema
 Through / Peak (T/P) Ratio

• Guidelines for the Clinical Evaluation

of Antihypertensive Drugs 1988
(Cardio-renal Division of FDA) :
• The drug effect at trough
(measured as the difference from
the placebo effect) should be no less
than 1/2 to 2/3 of the peak effect,
depending on the magnitude of the 25
 Through / Peak Ratio of diltizem® CD 72 %
Diltiazem Hydrochloride Sustained Released on Essential Hypertension Evaluated by 24-
hour Ambulatory Blood Pressure Monitoring (ABPM)

Oiwa J et al., Pharma Medica 18 (5) : 139-147 : 2000

 Hypertension Efficacy of HERBESSER® CD
 Clinical Effect of Diltiazem Hydrochloride Sustained Released Preparation
(HERBESSER® CD) on Essential Hypertension
– A Double Blind Study with Diltiazem Hydrochloride Current Product

** : p<0.01 (vs baseline) Mean + S.D. n = 37 Subject : Essential hypertension ( mild to moderate ) 53 cases
Method : HERBESSER® CD 100-200 mg once a day for 12 weeks

K. Arakawa et al, J. Clinical Therapeutics & Medicines 1989 ; 5: 171

Cardio Protective Effect of HERBESSER CD
( DRS Study )

28
 Summary:
• Prevalence of hypertension in the elderly
is quite high ( 60%-71%).
• There is convincing evident that treatment
of hypertension in the elderly is beneficial,
it will reduce cardiovascular morbidity
and mortality.
• Blood pressure reduction is more
important than specific drug.
• Low dose diuretic is the first line drug
• Selection of the drugs depend on the
comorbid disease.
29
 PENANGANAN
KRISIS HIPERTENSI
 Prevalensi:
› 1% dari penderita hipertensi
› 25% dari pasien hipertensi yang datang ke
instalasi gawat darurat

 Terjadi pada penderita hipertensi

sebelumnya, biasanya karena tidak
minum obat, atau terapi tidak adekuat

Kaplan 1998
DEFINITION :
HYPERTENSIVE CRISIS
A severe elevation in BP, generally a SBP > 220 mm Hg and / or
DBP > 120 mm Hg. (JNC-VI, 1997)
1. HYPERTENSIVE EMERGENCIES
Severe elevation in BP complicated by acute target organ
dysfunction, such as coronary ischemia, stroke, intracerebral
hemorrhage, pulmonary edema, or acute renal failure.
2. HYPERTENSIVE URGENCIES
Severe elevations in BP without evidence of target organ
deterioration.

Colhum DA. Oparil S, New Engl. J. Med, 323 : 1177, 1990

HYPERTENSIVE CRISIS
(usually) DBP >130 mmHg
URGENCY
 BP within hours < 24 hours
(PARENTERAL / ORAL)
KAPLAN NM . Lancet 344:1335,1994
EMERGENCY
 BP within minutes < 1 hours
(PARENTERAL)
- Accelerated malignant hypertension
- Hypertensive encephalopathy
- Intracerebral/Subarachnoid hemorrhage
- Acute aortic dissection
- Acute left ventricular failure
- Acute myocardial infarction
- Acute glomerulonephritis
- Eclampsia
- Severe epistaxis
- Perioperative hypertension
MANAGEMENT OF HYPERTENSIVE EMERGENCIES
JNC-VI RECOMMENDATION

• Reduce Mean Arterial BP no More than 25 %

over 2 hours then Reduce to 160 / 100 mm Hg
within 2-6 hours.

• Avoid excessive falls in Blood Pressure

• Titrate with Intravenous antihypertensives.

• Guideline of treatment based on concensus
expert.
 Tekanan darah

Vasokonstriktor Iskemi organ target

Tahanan perifer
Kerusakan endotel,
Deposisi fibrin dan
trombosit, hilang
fungsi
Nekrosis fibrinoid autoregulasi
arteriol

Kaplan 1998
 Jika tidak diobati:
› Kebanyakan meninggal dalam 6 bulan
› Harapan hidup setahun 10-20%

 Jika diobati:
› Harapan hidup 5 tahun > 70%

Kaplan 1998
 Factors in the pathomechanism of
hypertensive crisis

CONTRIBUTING TO CRITICAL INCREASE IN BP

LOCAL FACTORS SYSTEMIC FACTORS

• FG, Free radicals • Renin, A II, catecholamine,
• Endothelial damage ET
• Platelet-aggregation • Vasopressin, pressure
• Mitogenic and migration factors natriuresis
proliferation • Hypovolemia
• Myointimal proliferation

FURTHER INCREASE IN BLOOD PRESSURE AGGRAVATED

ENDOTHELIAL DAMAGE LEAD TO TISSUE ISCHEMIA
Kaplan, N : Critical Hypertension
 Subjective and Laboratory
Symptoms of Hypertensive Crisis

General symptoms
Cardiac symptoms Cerebral symptoms
sweating
palpitation headache
flush
rhythm disturbances dizziness
pallor
Chest pain nausea
dizziness
dyspnea daze
fear of death
focal symptoms
tinnitus
cramp
epistaxis
coma

Renal symptoms Ocular symptoms

oliguria flashes
hematuria spotted vision
proteinuria dimmed vision
Electrolyte disturbances diplopia
azotemia blindness
uremia Zamplagione B et al : Hypertension 1996
 Accelerated-malignant hypertension with papilloedema
 Cerebrovascular
› Hypertensive encephalopathy
› Atherothrombotic brain infarction with severe hypertension
› Intracerebral hemorrhage
› Subarachnoid hemorrhage
› Head trauma
 Cardiac
› Acute aortic dissection
› Acute left ventricular failure
› Acute or impending myocardial infarction
› After coronary bypass surgery
 Renal
› Acute glomerulonephritis
› Renal crises from collagen vascular disease
› Severe hypertension after kidney transplantation

 Excess circulating catecholamines

› Pheochromocytoma crisis
› Food or drug interactions with monoamine-
oxidase inhibitors
› Sympathomimetic drug use (cocaine)
› Rebound hypertension after sudden cessation of
antihypertensive drugs
› Autonomic hyperreflexia after spinal cord injury
 Eclampsia
 Surgical
› Severe hypertension in patients requiring
immediate surgery
› Postoperative hypertension
› Postoperative bleeding from vascular suture
lines
 Severe body burns
 Severe epistaxis

Kaplan 1998
 Secara umum:
› Prinsip utama: mencegah kerusakan organ
target  secara bertahap menurunkan
tekanan darah sambil meminimalkan hipoperfusi
jaringan

› Tentukan diagnosa: - hipertensi emergensi

- hipertensi urgensi
(riwayat penyakit, pem. fisik,
foto toraks, lab)
  Obat secara intravena
 Penanganan secara intensif
 Perlu diperhatikan karakteristik masing-
masing obat
 Tekanan darah diturunkan secara
bertahap
tek. darah rata-rata  25% tek. darah
awal (dalam beberapa menit – 4 jam),
kemudian dipertahankan tidak kurang
dari 160/100 mmHg
 Obat Mekanisme Efek samping
kerja
Nitroprusid Vasodilator arteri dan Mual, hipotensi, keracunan tiosianat dan
vena sianid
Nitrogliserin Vasodilator vena Sakit kepala, mual, takikardi, toleransi
Diaksosid Vasodilator Mencetuskan iskemi, retensi natrium
Hidralasin Vasodilator Laju jantung meningkat, sakit kepala, angina
Nikardipin Antagonis kalsium Hipotensi, takikardi, mual, muntah
Trimetafan Penyekat ganglion Hipotensi, takifilaksis, efek ortostatik
Labetalol Penyekat  dan  Mual, bronkospasme, bradikardi, blok jantung
Urapidil Penyekat  dgn Hipotensi, sakit kepala, melayang
aktivitas agonis
serotonin sentral
Fentolamin Penyekat  Takikardi, sakt kepala, angina
Esmolol Penyekat  Hipotensi, mual
Enalaprilat Penghambat EKA Hipotensi, gagal ginjal
Fenoldopam Agonis dopamin Sakit kepala, hipotensi
Diltiazem Antagonis kalsium Bradikardi, sakit kepala, flushing
Grosman. ACC Current J 1999
 COMMONLY USED DRUG IN HYPERTENSIVE EMERGENCY

DILTIAZEM I.V. (HERBESSER)

• Useful for hypertensive emergency and urgency.
• Acts as calcium slow-channel blockers.
• Rapidly and gradually reduced BP.
• Predictable onset of action.
• Adverse effect : bradycardia, hypotension, headache, flushing.
• Has antiischemic effect
• Has antiarrhythmic effect (class-IV)
Organ targets HER CLON NTG NIFE

Cardioprotective
Heart rate
Dilate: coroner ++ - ++ +
Ischemic

collateral ++ - - -
Anti-

Antiarrhytmic + - - -
Vasospasm ++ - - +
Renoprotective
Afferent + - - +
GFR & RBF - -
Efferent + - - -
CGP - -
Cerebroprotective
CBF
Epstein M, 1991, Bakris GL, 1993, Mancia G, 1996, Messerly FH, 1996
HERBESSER-Injection (diltiazem HCl)
Dosage and Administration
Each ampoule of HERBESSER-Injection should be dissolve in aquadest or
NaCl or dextrose or glucose solution before use.

BOLUS I.V. INJECTION

0.20 – 0.35 mg/kg BW
Adult (50kg) : 1 Ampoule (1 – 3 minutes)

DRIP I.V. INFUSION (Flat)

5 – 15 mcg/kg BW/min
Adult (50kg) : 15mg/hour – 45 mg/hour

DRIP I.V. INFUSION (maintenance)

1 – 5 mcg/kg BW/min
Adult (50kg) : 5mg/hour – 15 mg/hour
HERBESSER  Injection
Dose Flow Chart

Intravenous bolus injection

0.2 mg / kgBW

Intravenous drip infusion 10-20 % MBP reduction

from baseline
( 5-15 ug / kgBW / minute )

Observe every 30-60 minutes

Stable BP
Switch to oral HERBESSER® CD 200
 Bila mungkin, identifikasi dan atasi
penyebab ( misal: analgetik /
antiansietas untuk nyeri )
 Awal: tempatkan pada suasana tenang,
30 menit kemudian ukur ulang TD
 Obat-obat antihipertensi oral (JNC VI)
 Penurunan tekanan darah bertahap 24-
48 jam. Penurunan mendadak ( terutama
usia lanjut ) mengurangi aliran ke
jantung, otak, dan ginjal mengakibatkan
 stroke, infark miokard dan iskemia
ginjal.
 Perhatikan:
› Sifat obat
› Mekanisme kerja obat
› Efek samping obat
 Obat Mekanisme Keterangan
kerja
Kaptopril Penghambat EKA Kontraindikasi pada stenosis arteri renalis

Nitrogliserin Vasodilator Direkomendasikan pada pasien iskemi koroner

Nifedipin Antagonis kalsium Jangan gunakan bentuk kapsul sublingual. Bisa

takikardi
Nitrendipin Antagonis kalsium Bisa menyebabkan hipotensi berat

Nikardipin Antagonis kalsium Menyebabkan hipotensi

Isradipin Antagonis kalsium Menyebabkan hipotensi

Labetalol Penyekat  dan  Jangan digunakan pada PPOK, gagal jantung

Klonidin Agonis  Bisa hipertensi bila distop tiba-tiba

Furosemid Diuretik Bisa digunakan bila obat-obat lain telah

digunakan

Grosman. ACC Current J 1999

 CONCLUSION

PERI-OPERATIVE HYPERTENSION
• Peri-operative hypertension, as part of hypertensive emergency should
be treated promptly and appropriately.
• Antihypertensive agent should be given parenterally to avoid rebound
hypertension and to minimize target organ damage.

FOR ORGAN TARGET PROTECTION

• Diltiazem effective in Target Organ Protection:
•CARDIO-, RENO-, CEREBRO- PROTECTION

DILTIAZEM INTRAVENOUS
Diltiazem intravenous : SCALABE and PREDICTABLE
• EFFECTIVE to lower blood pressure FASTER in avoiding complication of
hypertensive emergency.
 Hipertensi emergensi: turunkan tekanan
darah segera untuk mencegah
kerusakan organ target lebih lanjut.
Penurunan tekanan darah 25% dalam 2 -
4 jam pertama. Kondisi spesifik perlu
penanganan yang berbeda.
 Hipertensi urgensi: tidak ada bukti yang
mendukung bahwa penurunan tekanan
darah secara cepat menguntungkan.
Tekanan darah diturunkan dalam 24-48
jam, obat secara oral.