Transcript aritmia cordis - WordPress.com

CLINICAL PHARMACOLOGY:
CARDIOVASCULAIR
SULANTO SALEH-DANU R., dr.,SpFK
DEPT. OF PHARMACOLOGY and THERAPY
DIV. OF CLINICAL PHARMACOLOGY
FACULTY OF MEDICINE – GMU
1
-DISTRIBUTION :
OKSIGEN, NUTRIEN,
WATER, ELEKTROLIT,
VITAMIN, HORMON,
MEDICINES etc,etc.
to our organ and tssues.
HEART
PUMPING : OXYGEN and
NUTRIEN to whole organ
and tissues
VESSELS
CARDIOVASCULAR
-CARRYING and
-TRANSPORTING : Carbon
dioxyde; metabolism
production, metabolism
residual
- CONTRIBUTOR : immune sys
- TERMOREGULATION
‘ROAD’ / pipe for distribution
Oxygen and Nutrient
BLOOD
 CARRYING MATERIAL &
“GARBAGES” from
the body to out side .
2
HEART
As a PUMP: pumping the blood
to whole body
Blood vessels : limited capacity
ELECTRICAL CONDUCTION SYST.:
to maintain the heart rate
and rhythm
HEART MUSCLE (MYOCARDIUM) :
need OXYGEN and other “food”
for the activity
3
SEORANG ANAK PEREMPUAN 7 TAHUN,DIBAWA ORANG TUANYA
UNTUK PERIKSA PADA SAUDARA KARENA ANAKNYA MENDERITA
DEMAM KURANG LEBIH SEMINGGU; MENGELUH SENDI-2 NYA
NYERI/SAKIT; KEJADIAN INI PERNAH DIALAMI BEBERAPA
WAKTU YANG LALU; KADANG-KADANG BICARA TAK JELAS;
TAK BISA BERGERAK/LEMAH
PADA PEMERIKSAAN SUHU 39°C; CHOREA, ERITEMA, ARTHRITIS.
UTK KONFIRMASI DILAKUKAN PEMERIKSAAN PENUNJANG :
DARAH RUTINE LENGKAP , KIMIA DARAH, dan EKG
1.. PROBLEM ?
2. OBJEKTIF ?
3. PEMILIHAN TERAPI  NON FARMAKOLOGIK
 FARMAKOLOGIK
4. PERESEPAN ?
5. INFORMASI, INSTRUKSI dan PERINGATAN-2 ?
6. MONITORING – EVALUASI INTERVENSI ?
4
HEART DISEASES
HYPERTENSION;
 CONGESTIVE HEART FAILURE
or DECOMPENSATIO CORDIS;
ANGINA PECTORIS
( CHEST-PAIN 
ACUTE MYOCARDIAC INFARCTION);
 CARDIAC ARRHYTMIAS.
5
KELAINAN/PENYAKIT
CARDIOVASCULAR
PADA :
NEONATUS ?
INFANTS ?
CHILDREN ?
ADOLESCENS ?
6
HYPERTENSION
7
Hypertension
SBP > 140 mmHg
DBP> 85 mmHg
Vital organs
risk
Heart
Coronary
factors
Myocardium
factors
CHD
LVH
Congestive heart failure
Arrhythmia
cordis
Sudden death
• Stroke
• Multi infarct dementia
• Peripheral vascular
disease
• Aortic aneurysm
• Renal failure
Disability
8
R. Boedhi Darmojo, 2000, WHO-ISH, 1999
Goal 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. VII, 03, WHO – ISH, 1999
9
Management Strategy Assessed The
Patient Risk Profile
Blood Pressure (mm Hg)
Grade I (mild)
Grade II
(moderate)
Grade III
(severe)
SBP:140-159
160-179
> 180
DBP:90-99
100-109
> 110
I. No Other Risk Factors
LOW RISK
MED RISK
HIGH RISK
II. 1-2 Risk Factors
MED RISK
MED RISK
V. HIGH RISK
III. 1-2 Risk Factors or TOD
or Diabetes
HIGH RISK
HIGH
V. HIGH RISK
IV. Associated Clinical
Condition
V. HIGH RISK
V. HIGH
RISK
V. HIGH RISK
Risk Factors & Disease
History
WHO – ISH, 1999
10
CARDIOVASCULAR RISK FACTORS;
MAYOR RISK FACTORS :
• Hypertension (as components of metabolic syndrome)
• Cigarette smoking
• Obesity ( BMI ≥ 30 )
• Physical inactivity
• Dyslipidemia
• Diabetes mellitus
• Microalbuminuria or estimated GFR< 60 ml/min
• Age >55 years – men; > 65 years for women
• Family history of premature CV disease
11
Complications of hypertension
Brain  Strokes
TIA (transient ischemic attack)
Heart
 Left ventricular hypertrophy
 Coronary artery disease
 Myocardial infarction
 Heart Failure
 Arrhythmia
Kidney  Renal failure
Retinopathy
Aneurysm (rupture) of the aorta
Peripheral artery disease
12
When Starting
PHARMACOTHERAPEUTICS
• Fail non pharmacotherapy
• Low risk (during 6-12 mo)
– SBP > 150 mm Hg
– DBP > 95 mm Hg
• Med risk (during 3-6 mo)
– SBP > 140 mm Hg
– DBP > 90 mm Hg
• High & very high risk
– Must be direct pharmacotherapy
13
ANTIHYPERTENSIVE AGENTS (CLASSES)





DIURETICS
β- BLOCKERS
ACE-inhibitors
CALCIUM CHANNEL BLOCKERS
ARBs (angiotensine receptor blockers)





INITIAL
PHARMACOTHERAPY
aldosterone receptors antagonists
α– adrenoceptor antagonists
central sympatholytic actions
arteriolar dilators
peripheral sympathetic inhibitors
14
Pharmacotherapy based on : Efficacy, Safety, + Costly (WHO-ISH,
1999)
Class of
drug
Compelling
indication
Possible
indications
Compelling C.I
Diuretics
•Heart Failure
•ELDERLY
•Systalic hypertension
Diabetes
Out
ß-Blockers
• Angina
• After M.I
• Tachyarrhythmia
Heart Failure
Pregnancy
Diabetes
•Asthma & CoPD
•Heart Block
(gr 2/3 AV)
•Phslipidemia
•Athletes, physically active
patients
•Peripheral vascular disease
Calcium
antagonists
•Angina
•ELDERLY
•Systolic hypertension
Peripheral
vascular disease
Heart block
Congestive heart failure
ACE
inhibitors
•Heart Failure
•LU Dysfunction
•After myocardial infarct
 - Blocker
Prostatic hypertrophy
Angiotensin II Ace – inhibitor cough
Receptor
antagonist
Possible C.I
•Pregnancy
•Hyperkalaemia
•Renalartery stenosis
(bilateral)
•Glucose
intolerance
•dyslipidemia
Heart failure
Orthostatic hypotension
•Pregnancy
•Hyperkalaemia
•Renalartery stenosis
(bilateral)
15
Choice of initial drugs
 Diuretics
 β - blockers
 Calcium channel blocker
 ACE inhibitor
 AIIRA / ARB
16
Pharmacotherapy
hypertension ( in Elderly )
Diuretic
Calcium channel blocker (calcium antagonist)
Dihydropyridines
Non dihydropyridines
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nisaldipine
2,5- 10 mg
2,5- 20 mg
5 - 20 mg
60 - 40 mg
30 –120 mg
20 – 60 mg
Benzothiazepin (diltiazem) 120 – 360 mg
Phenylalkilamine
50 – 100 mg
(mibefrazil)
Veropamil
90 – 180 mg
17
STEP CARE: RIGID VS LIBERAL
Old
Some variation of :
1. Diuretic or β-blocker
New approach
Evidence based and patient
guided choice
2. Vasodilatation
3. Combination
4. Central agents
ARB
Diuretics
ACEI
β - blocker
CCB
18
Choice of the initial drugs
 Should tailored to the patients, for example
in gout do not administered thiazide
 In asthmatic patients do not give beta
blocker.
 In “blacks people” ACE inhibitor or
beta-blockers are not very effective
19
LIFE STYLE MODIFICATION FOR HYPERTENSION PREVENTION and
MANAGEMENT
 Lose weight if overweight
 Limit alcohol intake to no more than 1 oz (30 mL) ethanol {e.g., 24
oz (720 mL) beer, 10 oz (300 mL) wine, or 2 oz (60 mL) 100-proof
whiskey} per day or 0.5 oz (15 mL) ethanol per day for women and
lighter weight people.
 Increase aerobic physical activity (30 to 45 minutes most days of
the week).
 Reduce sodium intake to no more than 100 mmol per day (2.4 g
sodium or 6 g sodium chloride).
 Maintain adequate intake of dietary potassium (approximately
90 mmol per day).
 Maintain adequate intake of dietary calcium and magnesium for
general health.
 Stop smoking and reduce intake of dietary saturated fat and
cholesterol for overall cardiovascular health.
20
CONGESTIVE HEART FAILURE
(CHF)
DECOMPENSATIO CORDIS
GAGAL JANTUNG
21
CONGESTIVE HEART FAILURE
DECOMPENSATIO CORDIS
GAGAL JANTUNG
Cardiac output is inadequate to provide
the oxygen needed by the body
SYSTOLIC FAILURE : the mechanical pumping
(contractility) and the ejection fraction of the reduced.
DIASTOLIC FAILURE : stiffening and loss of
adequate relaxation plays a mayor role
reducing the cardiac output .
22
CONGESTIVE HEART FAILURE
(CHF)
DECOMPENSATIO CORDIS
GAGAL JANTUNG
CONGESTIVE / CHRONIC
Increased exertion
Emotion
Salt in diet
Noncompliance
etc.
ACUTE H F/PULMONARY EDEMA
23
STRATEGY CHF
1. CORRECTION THE REVERSIBLE CAUSES;
2. INCREASING MYOCARDIAC CONTRACTILITY;
3. REDUCING CARDIAC PRELOAD
(blood volume filling heart ventricle
during diastolic phase);
4. REDUCING CARDIAC AFTERLOAD
( pressure needed for pumping the blood
to the circulation systems ;
Systolic phase)
NON-PHARMACOTHERAPY
PHARMACOTHERAPY
24
TREATMENT OF CHRONIC H F :
1. Reduce workload of the heart
a. Limit activity, put on bed rest
b. Reduce body weight
c. Control hypertension
2. Restrict sodium intake
3. Restrict water
4. Give diuretic
5. Give ACE inhibitor or ARB
6. Give digitalis
(if systokic dysfunction with 3rd heart soundor
atrial fibrillation present)
7. Give β-blocker
(to patients with stable class II-IV HF)
8. Give vasodilators
9. Cardiac resynchronization if
wide QRS interval is present in normal sinus
rhythm.
25
PHARMACOTHERAPY










DIURETICS
ALDOSTERONE RECEPTOR ANTAGONIST
ACE – inhibitors
ANGIOTENSIN RECEPTOR BLOCKERS
BETA – blockers
CARDIAC GLYCOSIDES / CARDIOTONIC
VASODILATORS
BETA AGONISTS, dopamine
BIPYRIDINES
NATRIURETIC PEPTIDE
(Katzung,BG et al., 2007)
26
MECHANISM and SITE OF ACTION
DRUGS USE IN CONGESTIVE HEART FAILURE
1. DIGOXIN (an alkaloid GLYCOSIDE / CARDIOTONIC)
 increase myocardium contractility by increasing calcium penetration to
myocardium
DOBUTAMINE ( SYMPATHOMIMETIC Group )
 increase myocardium contractility by increasing production cAMP in
bounding β1 -receptor.
2. DIURETICs Group;
 reducing afterload by reducing blood volume ( increase of urine excretion )
3. Angiotensin Converting Enzym (ACE) – Inhibitors / ARBs:
CAPTOPRIL; CANDESARTAN; dll.
 the effect dilatation peripheral blood vessels  cause decreasing
afterload
4. HYDRALAZINE  relaxation of arteriole  decreasing afterload
27
HAL-HAL YANG PERLU DIPERHATIKAN PADA
PENDERITA GAGAL JANTUNG:
1. INTERAKSI DIGOKSIN dengan
- CALCIUM  POTENSIASI DIGOKSIN.
- QUINIDIN ( golongan ANTIARITMIA CORDIS )  kadar DIGOKSIN
meningkat ( ikatan dengan protein )
2. MAKANAN / NUTRISI : JANGAN diberikan yang memperberat
kerja jantung atau yang BERINTERAKSI dengan OBAT-OBAT yang
digunakan.
3. Untuk DIGOKSIN, salah satu sifat obat ini di akumulasi ditubuh, cara
pemakaian harus memperhatikan besar obat yang diekresikan dalam
24 jam. Waktu paruh panjang ( 40 - >160 jam ).
28
ANGINA PECTORIS
CHEST PAIN
NYERI DADA
29
DRUGS USED IN THE TREATMENT
OF ANGINA PECTORIS.
 angina pectoris refers to a strangling or pressure-like pain
caused by cardiac ischemia.
The pain is usually located sub sternally but sometimes
perceived in the neck, shoulder, or epigastrium.
Type of ANGINA
 UNSTABLE ANGINA
= CRESCENDO ANGINA
= ACUTE CORONARY SYNDROME
 ATHEROSCLEROTIC ANGINA
= CLASSIC ANGINA
= ANGINA OF EFFORT
 VASOSPASTIC ANGINA
= REST ANGINA
= VARIANT ANGINA
= PRINZMETAL’S ANGINA
30
ANGINA PECTORIS
impairment oxygenation of the heart muscle
Imbalancing the supply to the need of oxygen
of the heart muscles (myocardium)
CHEST PAIN (left side) and/or
DYSPNEA,
EPIGASTRIC PAIN
31
... major determinant of coronary insufficiency :
myocardial fiber tension ( the higher the tension,
the greater the oxygen requirement ).................
MYOCARDIAL OXYGEN REQUIREMENT
INTRAMYOCARDIAL FIBER TENSION
+
+
BLOOD VOLUME
+
VENOUS TONE
DIASTOLIC FACTORS
+
PERIPHERAL
RESISTANCE
+
HEART
RATE
+
EJECTION
TIME
HEART
FORCE
SYSTOLIC FACTORS
32
STABLE ANGINA
Vasospasm may
reduce supply
Effort
increases
demand
Symptoms:
Crushing sensation
in chest or neighbouring areas
 Associated with effort
 Relieved by rest or
nitroglycerin
Diagnosis
 Possible resting ECG changes
during exercise stress test :
- ST segment elevated or depressed
- arrhythmias
- decreased BP
- ischaemic myocardium revealed by
thallium-201 or MIBI imaging
 Angiography shows
coronary artery disease
33
VARIANT ANGINA = vasospastic angina = Prinzmetal’s angina
Symptoms
-- angina pain at rest
-- angina not effort-related
-- often occurs on early morning
-- exacerbated by smoking
Diagnosis
-- ST segment elevation during
pain
-- angina induced by ergonovine
-- angoigraphy may not reveal
coronary artery diseases
-- exercise stress test of little value
Variant angina, in which vasospasms is the primary cause of coronary insufficiency,
is must less common than stable angina. However, vasospasms is often a
contributing factor in both stable and unstable angina.
34
Drugs used in angina pectoris
Vasodilators
Nitrates
Cardiac depressants
Calcium blockers
Beta-blockers
Long duration
Intermediate
Short duration
(Trevor,AJ; Katzung,BG; Masters,SB; 2005)
35
OBAT-OBAT YANG DIGUNAKAN
PADA SERANGAN ANGINA (ANGINA PECTORIS)
AIMS :  mengatasi nyeri dada atau mencegah timbulnya nyeri dada
 menghambat progresi dari atherosclerosis
 memperbaiki prognosis
SERANGAN AKUT :
 NON-FARMAKOTERAPI : segera diistirahatkan begitu serangan
nyeri muncul, baringkan pada tempat yang aliran udara baik.
 FARMAKOTERAPI :
- GLYSERIL TRINITRAT spray 400 mcg/metered dose, sublingual,
diulang tiap 5 menit sampai nyeri hilang/berkurang atau
- GLYSERIL TRINITRATE tablet 300 – 600 mcg s.l. diulang tiap
3-5 menit sampai mencapai dosis max 1.800 mcg atau
- ISOSORBIDE DINITRATE tablet 5 mg, diberikan s.l.. Diulang
tiap 5 menit. Maksimum 3 tablet.
HINDARI PEMAKAIAN PREPARAT NITRATE BERSAMA-SAMA DENGAN
SILDENAFIL (dalam waktu 24 jam) atau TADALAFIL (dalam waktu 5-6 hari)
36
CALCIUM CHANNEL-BLOCKING MEDICINES
DIHYDROPYRIDINE :
NON-DIHYDROPYRIDINE :
 amlodipine
 felodipine
 nicardipine
 nifedipine
 nimodipine
 nisoldipine, etc.
 bepridil
 diltiazem
 verapamil
VASODILATATION
37
β-ADRENOCEPTOR-BLOCKING AGENTS
 obat-obat yang bekerja menghambat
reseptor β serabut syaraf syaraf simpatis
Pada angina hal-hal yang menguntungkan :
- menurunkan heart rate
- tekanan darah turun
- kontraktilitas otot jantung turun.
kebutuhan oksigen otot jantung turun
38
β – BLOKER AGENTS :
- Atenolol
- Carvedilol
- Labetalol
- Metopolol
- Nadolol
- Pindolol
- Propranolol
- Timolol, etc.
39
Adverse Drug Reaction
Impaired/
failure
organ
Multiple
disease state
polypharmacy
compliance
Altered organ
response
Altered drug
concentration
Adverse Drug
Reactions
Homeostatic
regulation
40
OXYGEN CONSUMPTION
ANGINA ATTACK
LONGTERM / UNCONTROLED
MYOCARD INFARCTION
CARDIAC ARREST  DEATH
41
CARDIAC ARRHYTHMIAS
ARITMIA CORDIS
42
ARITMIA CORDIS : malfunction of the electrical impuls
conduction in the heart.
ARITMIA CORDIS :
1. DECREASING THE HEART RATE  SINUS BRADYCARDIA
2. INCREASE THE HEART RATE  SINUS or VENTRICULAR TACHYCARDIA;
ATRIAL or VENTRICULAR PREMATURE DEPOLARIZATION;
ATRIAL FLUTTER)
3. INCOORDINATION / AUTONOM OF THE IMPULS CONDUCTION (ATRIAL
FIBRILLATION; MULTIFOCAL ATRIAL TACHYCARDIA; VENTRICULAR
FIBRILLATION)
4. NEW PATHWAY OF THE ELECTRICAL CONDUCTION (A – V REENTRY;
W-P-W / Wolff-Parkinson-White SYNDROME)
43
ARITMIA CORDIS CLASSIFICATION
ARITMIA CORDIS from ATRIUM :
 SINUS BRADYCARDIA
 SINUS TACHYCARDIA
 MULTIFOCAL ATRIAL TACHYCARDIA
 PREMATURE ATRIAL DEPOLARIZATION (PAT)
 ATRIAL FLUTTER
 ATRIAL FIBRILLATION
ARITMIA CORDIS from VENTRICLE :
 VENTRICULAR TACHYCARDIA
 VENTRICULAR FIBRILLATION
 VENTRICULAR PREMATURE DEPOLARIZATION
ARITMIA CORDIS conduction from Atrium  Ventricle:
 A – V REENTRY
 W-P-W SYNDROME
44
PHARMACOTHERAPY
ARITMIA CORDIS
CLASSIFICATION : I; II; III; IV dan Unclassified ) :
Ia : action prolong the action potential duration (APD) and dissociate from
the channel with intermediate kinetics;
Ib : action shorten the APD in some tissue of the heart and dissociate from
the channel with rapid kinetics;
Ic : action have minimal effect on the APD and dissociate from the channel
with slow kinetics;
II : action is sympatholytic. Drugs with this action reduce β-adrenergic
activity in the heart ;
III : action is manifest by prolongation of the APD. Most action block
the rapid component of the delayed rectifier potassium current ( IKr );
IV : action is blockade of the cardiac calcium current. This action slows
conduction in region where the action potential upstroke is calcium
dependent, eg the sinoatrial and atrioventricular nodes;
Others : the effect depress ectopic focal of the heart.
45
CLAS Ia : quinidine; procainamide; disopyramide (norpace)
CLAS Ib : lidocaine (xylocaine); mexiletine; tocainide
CLAS Ic : flecainide; indecainide; propafenone (rythmonorm);
moricizine
CLAS II : propranolol; esmolol; sotalol
CLAS III: amiodarone; bretylium; dofetilide; ibutilide
CLAS IV: verapamil; diltiazem
Others : adenosine; digoxin; magnesium sulfate
46
47
VASODILATOR
systemic vascular
resistance
sympathetic nervous
system outflow
arterial pressure
Sodium excretion
renin release
aldosteron
angiotensin II
heart rate
systemic
vascular
resistance
sodium retention
plasma volume
arterial blood pressure
venous
capacitance
cardiac
contractillity
cardiac output
48