HER CCB in Crisis Hypertension
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Transcript of HER CCB in Crisis Hypertension
The Role of Diltiazem in the Management of Emergency
Hypertension
JNC VII Recommendation:
The Initial Goal of Therapy in Hypertensive Emergency Is to
Reduce MABP by No More Than 25% (within minute to 1 hour), then if stable, to 160/100-110 within the
next 2-6 hours.
JNC 7, The Lancet 2003
Consensus in the treatment of Crisis Hypertension (InaSH 2008)
Blood Pressure reduction target of crisis hypertensive patients:
– Parenteral anti hypertension is given based on the procedure of crisis hypertensive treatment with MAP reduction 20-25% from the baseline in the first hour.
– Target of BP reduction is 160 mmHg for Systolic and 90 mmHg for Diastolic.
•Konsensus Penanggulangan Krisis Hipertensi (InaSH 2008)
Drugs used in the emergency hypertension (InaSH 2008)
B. Diltiazem (Herbesser) IV (50 mg/ampul)– Diltiazem 10mg IV given by bolus in 1-3 menit
followed by drip infusion 50 mg/jam in 20 menit.
– When the BP reduction achieve at >20% from the baseline, the dosage is adjusted to 30 mg/jam until the BP reduction target achieved.
– Followed by maintenance dosage 5-10 mg/jam, observed in 4 hours, if stabil switch to oral.
– Precaution to the patients with AV Block and Heart Failure.
•Konsensus Penanggulangan Krisis Hipertensi (InaSH 2008)
Management of Hypertension in the stroke acute patient
I. Guidance in the acute ischemic stroke:1.Management of HypertensionBlood
Pressure elevation:• For patient with Diastolic Blood Pressure >
140 mmhg (or > 110 mmhg if in trombolytic treatment) is treated as emergency hypertensive patient and should receive drip continue; nikardipin, diltiazem, nimodipine, etc.
Guideline Stroke PERDOSSI 2011, BAB V hal 46.
Drugs used in the treatment of emergency hypertension (InaSH 2008, CHEST 2007)
• Clonidin (Catapres) IV (150 mcg/ampul)• Diltiazem (Herbesser IV); 50 mg/ampul Nicardipin (Perdipin IV (2 mg dan 10 mg/ampul) Labetalol (Normodyne) IV* Nitroprusside (Nitropress, Nipride) lV Nitroprusside in drip infus with dosage dosis
0.25-10.00 mcg/kg/menit Nitogliserin (nitrat)
•Chest 2007;131;1949-1962•Konsensus Penanggulangan Krisis Hipertensi (InaSH 2008)
Calcium Channel Blockers
Which one for which condition?
Actions of Calcium Channel Blockers on Smooth Muscle and Heart
Calcium Channel BlockersCalcium Channel Blockers
Slow Ca2+ entrySlow Ca2+ entry
Smooth muscleSmooth muscle Heart muscleHeart muscle
Oesophagus Ureter Detrusor vesicae Uterus Intestine Bronchi
Oesophagus Ureter Detrusor vesicae Uterus Intestine Bronchi
Blood vessels Blood vessels
Coronary flow Vasospasm Organ protection
Coronary flow Vasospasm Organ protection
AtherosclerosisAtherosclerosis Blood pressureBlood pressure
Sinus rate AV conduction
Sinus rate AV conduction
Contractility Cardioprotection
Contractility Cardioprotection
Dihydropyridine ( DHP ) Nifedipine, Amlodipine, Felodipine Non-Dihydropyridine ( NDHP ) Diltiazem, Verapamil
OPIE, 2001
Calcium Channel Blockers ( CCBs )
Calcium Channel Blockers
Nicardipine(dihydropyridine)
Diltiazem(benzothiazepine)
Peripheral Vasodilation1 +++++ +++
CoronaryVasodilation2 +++++ +++
Suppressionof SA Node2 + +++++
Suppressionof AV Node2 0 ++++
Suppressionof Cardiac Contractility2 0 ++
1. Frishman WH, et al. Med Clin North Am. 1988;72:523-547. 2. Adapted from Goodman and Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. 2001.
NICARDIPINE and DILTIAZEM
NICARDIPINE DILTIAZEM
Target organ Arteriole (ca Channel)
Arteriole (ca Channel)
Clinical effect Vasodilatation : BP decreased
Vasodilatation : BP decreased
Heart Rate ↑ ↓
Diltiazem and Nicardipine on HR of Hypertensive emergency patients
Nicardivine I.V. Diltiazem I.V
< 60 60 - 80 > 80
Heart Rate (beat/minute)
Clinical Data
Diltiazem Injection on Haemodynamic Control
50
100
150
200
250
50
75
100
0
5
10
15
0 0.5 1 2 3 4 5 6
250
200
150
100
50
75
50
0
10
5
0.5 1 2 3 4 5 6
Dose infused
g/kg/min
Pulse Rate
beats/min
Blood Pressure mmHg
2927
*24*
14*
14*
12*
9*
9*
* * * * * * *
* * * * * **
*******
* P0.05 vs
pretreatment level
Subjects: 29 severe systemic hypertension
Dosage : diltiazem initial dose less 10 g/kg/min, average infusion rate was 11 g/kg/min
Current Therapy Research. 1988: 43
SBP
mean
DBP
24.6%24.6%
26.9%26.9%
8.9%8.9%
205 mmHg
115.8 mmHg
154mmHg
83.3mmHg
87.178.1
Antihypertensive drugs and Heart Rate
16
Subject : 11 patients with hypertension emergency Design : Open study
Diltiazem injection Drip infusion: 5~40 μg/kg/min
Average BP reduced
224/119 mmHg to 170/95 mmHg (mean change 27.3 9.0 %, P<0.001)
HR controlled
17Current Therapeutic Research.1987: 42:1223.
Antihypertensive drugs and Heart Rate
Nicardipine i.v.
Hirayama A, Katayama Y, et al:Neurological Research 16; 97-99, 1994
35 patients who had surgical evacuation of spontaneous intracerebral haematomas after cerebral hemorrhage
Herbesser i.v.: 12, Nitroglycerin i.v.: 13, Nicardipine i.v.:10
Compare the intracranial pressure when the same blood pressure reduction level is achieved in each group.
①CPP index= CPP/ SBP△ △②CPP index coming close to 1 indicates less increase of intracranial pressure.
Comparison of intracranial pressure change by different antihypertensives.
Ch
an
ge
of
intr
acr
an
ial
pre
ssu
re
Comparison of Cerebral perfusion pressure index (CPP index) by different antihypertensives.
CP
P in
de
x
Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v.Herbesser i.v. Nitroglycerin i.v.
20
10
0
2.0
1.5
0.0
1.06.7
14.2
17.0
1.33±0.07
1.80±0.11
1.63±0.13
p<0.05
p<0.05
( mmHg )
Target
Medication
Methods
Antihypertensive drugs cause increase of ICP
Diltiazem i.v. reduced cardiac event rate Diltiazem i.v. reduced cardiac event rate in patients with unstable angina.in patients with unstable angina.
Target
Gobel E, et al. Lancet 346:1653-1657, 1995
Nitroglycerin i.v. group (n=61)
Herbesser i.v. group (n=60)
Inci
denc
e du
ring
i.v.(
%)
40
30
20
10
0Myocardial infarction refractory angina Myocardial infarction
+refractory angina
10
5
28
10
38
15
p=0.02*
p=0.007**
Methods
129 patients with unstable angina
Randomized, double blind comparative trialDiltiazem i.v. group (n=60) :25mg i.v.+5mg/h continuous i.v. (increase dose to 25mg/h)Nitroglycerin i.v. group (n=61) : Physiologic saline i.v.+1mg/h continuous i.v. (increase dose to 5mg)
Intravenous bolus injectionIntravenous bolus injection0.2 mg / kgBW0.2 mg / kgBW
Intravenous drip infusion Intravenous drip infusion ( 5-15 µg / kgBW / minute )( 5-15 µg / kgBW / minute )
10-20 % MBP reductionfrom baseline
Switch to oral HERBESSERSwitch to oral HERBESSER®® CD 200 CD 200
HERBESSERHERBESSER Injection InjectionDose Flow ChartDose Flow Chart
Stable BP
Observe every 10-20 minutes
Dose calculation
Dosis Berat Laju Infusi Mikrodrip Dosis Berat Laju Infusi Mikrodrip Dosis Berat Laju Infusi Mikrodripmcg/kg/mnt kg mg/jam tetes/menit mcg/kg/mnt kg mg/jam tetes/menit mcg/kg/mnt kg mg/jam tetes/menit
1 50 3 3 6 50 18 18 11 50 33 331 60 4 4 6 60 22 22 11 60 40 401 70 4 4 6 70 25 25 11 70 46 461 80 5 5 6 80 29 29 11 80 53 531 90 5 5 6 90 32 32 11 90 59 591 100 6 6 6 100 36 36 11 100 66 662 50 6 6 7 50 21 21 12 50 36 362 60 7 7 7 60 25 25 12 60 43 432 70 8 8 7 70 29 29 12 70 50 502 80 10 10 7 80 34 34 12 80 58 582 90 11 11 7 90 38 38 12 90 65 652 100 12 12 7 100 42 42 12 100 72 723 50 9 9 8 50 24 24 13 50 39 393 60 11 11 8 60 29 29 13 60 47 473 70 13 13 8 70 34 34 13 70 55 553 80 14 14 8 80 38 38 13 80 62 623 90 16 16 8 90 43 43 13 90 70 703 100 18 18 8 100 48 48 13 100 78 784 50 12 12 9 50 27 27 14 50 42 424 60 14 14 9 60 32 32 14 60 50 504 70 17 17 9 70 38 38 14 70 59 594 80 19 19 9 80 43 43 14 80 67 674 90 22 22 9 90 49 49 14 90 76 764 100 24 24 9 100 54 54 14 100 84 845 50 15 15 10 50 30 30 15 50 45 455 60 18 18 10 60 36 36 15 60 54 545 70 21 21 10 70 42 42 15 70 63 635 80 24 24 10 80 48 48 15 80 72 725 90 27 27 10 90 54 54 15 90 81 815 100 30 30 10 100 60 60 15 100 90 90
Contoh Perhitungan : I = ? Infusion Pump :Keterangan simbol : D = 5 mcg/kg/menit = 0.25 ml/menit x 60I = Infusion rate C = 0.1 % (gr/ml) 50 mg/50 ml ~ 100 mg/100 ml = 15 ml/jamD = Dosis (mcg/kg/menit) W = 50 kgC = Konsentrasi (%) Mikrodrip :W = Berat Badan (kg) Rumus / Formula : I = D/C x W = 0.25 ml/menit x 60
I = 5 mcg/kg/mnt / ( 50 mg/ 50 ml ) x 50 kg = 15 tetes/menit = 0.005 mg/kg/mnt x ( 50 ml/ 50 mg ) x 50 kg = 0.25 ml/menit
TABEL ALUR DOSIS PENGGUNAAN HERBESSER-INJ DRIP INTRAVENA
Effective in Controlling Blood Pressure with Target Organ Protection:
Predictable Onset of Action
Anti Ischemic and Arrhythmic Effect
Heart & Brain Protection.
Easy to Use
Intravenous Diltiazem HCl 50 mg
TERDAFTAR DI DPHO
ASKES HERBESSER Injection 50
®
Thank You