CLINICAL PHARMACOLOGY:

CARDIOVASCULAIR

-DISTRIBUTION :
OKSIGEN, NUTRIEN,
WATER, ELEKTROLIT,
VITAMIN, HORMON,
MEDICINES etc,etc.
to our organ and tssues.

CARDIOVASCULAR
-CARRYING and
-TRANSPORTING : Carbon
dioxyde; metabolism
production, metabolism
residual
- CONTRIBUTOR : immune sys
- TERMOREGULATION

HEART

PUMPING : OXYGEN and

NUTRIEN to whole organ
and tissues

VESSELS
ROAD / pipe for distribution
Oxygen and Nutrient

BLOOD

CARRYING MATERIAL &

GARBAGES from
the body to out side .

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 39C; 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

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

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

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
- BLOCKERS
ACE-inhibitors
CALCIUM CHANNEL BLOCKERS
ARBs (angiotensine receptor blockers)

INITIAL
PHARMACOTHERAPY

aldosterone receptors antagonists

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

-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

15

Choice of initial drugs

Diuretics
- 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 blocker
2. Vasodilatation
3. Combination
4. Central agents

New approach
Evidence based and patient
guided choice
ARB

Diuretics

ACEI

- 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

JNC VIII

Pada pasien 60 tahun atau lebih yang tidak memiliki

diabetes atau penyakit ginjal kronik, maka target terapi
tekanan darah sekarang <150/90 mHg.
Pada pasien 18-59 tahun tanpa kormobiditas mayor, dan
pada pasien 60 tahun atau lebih yang memiliki diabetes,
penyakit ginjal kronik, atau keduanya, maka target terapi
tekanan darah yang baru adalah <140/90 mmHg.
Terapi lini pertama dan selanjutnya sekarang harus
dibatasi menjadi empat golongan obat: diuretik-tipe
thiazide, calcium channel blocker (CCB), ACE Inhibitor, dan
ARB.
Alternatif lini kedua dan ketiga termasuk dosis yang
lebih tinggi atau kombinasi dari diuretik-tipe thiazide,
calcium channel blocker, ACE Inhibitor, dan ARB.

21

JNC VIII

Beberapa obat sekarang didesain sebagai alternatif lini

selanjutnya yaitu: beta-blockers, alphablockers,
alpha1/beta-blockers (mis. carvedilo), vasodilating betablockers (mis. nebivolol), central alpha2/-adrenergic
agonists (mis. clonidine), direct vasodilators (mis.
hydralazine), loop diuretics (mis. furosemide), aldosterone
antagoinsts (mis. spironolactone), dan peripherally acting
adrenergic antagonists (mis. reserpine).
Saat memulai terapi, pasien keturunan Afrika tanpa
penyakit ginjal kronik harus menggunakan CCB dan
thiazide daripada ACE Inhibitor.
Penggunaan ACE Inhibitor dan ARB direkomendasikan pada
seluruh pasien dengan penyakit ginjal kronik tanpa melihat latar
belakang etnis, baik sebagai terapi lini pertama atau sebagai22
tambahan pada terapi lini pertama.

JNC VIII
ACE Inhibitor dan ARB tidak boleh digunakan pada
pasien yang sama secara bersamaan.
CCB dan diuretik tipe thiazide harus digunakan daripada
ACE Inhibitor dan ARB pada pasien lebih dari 75 tahun
dengan fungsi penurunan fungsi ginjal karena adanya
risiko hiperkalemia, peningkatan kreatinin, dan penurunan
fungsi ginjal yang lebih parah.

23

CONGESTIVE HEART FAILURE

(CHF)
DECOMPENSATIO CORDIS
GAGAL JANTUNG

24

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 .
25

CONGESTIVE HEART FAILURE

(CHF)
DECOMPENSATIO CORDIS
GAGAL JANTUNG

CONGESTIVE / CHRONIC
Increased exertion
Emotion
Salt in diet
Noncompliance
etc.

ACUTE H F/PULMONARY EDEMA

26

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

27

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 -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.

28

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)

29

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 1 -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
30

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 ).

31

ANGINA PECTORIS
CHEST PAIN
NYERI DADA

32

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
= PRINZMETALS ANGINA
33

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

34

... 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
35

STABLE ANGINA

Vasospasm may
reduce supply

ents
v
e
r
is p pply
s
o
Sten ased su
e
i n cr

Symptoms:
Crushing sensation
in chest or neighbouring areas
Associated with effort
Relieved by rest or
nitroglycerin

Effort
increases
demand
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

36

VARIANT ANGINA = vasospastic angina = Prinzmetals angina

uces
d
e
r
m
s
Vasospa ply
sup

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.
37

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)

38

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)
39

CALCIUM CHANNEL-BLOCKING MEDICINES

DIHYDROPYRIDINE :

NON-DIHYDROPYRIDINE :

amlodipine
felodipine
nicardipine
nifedipine
nimodipine
nisoldipine, etc.

bepridil
diltiazem
verapamil

VASODILATATION
40

-ADRENOCEPTOR-BLOCKING AGENTS
obat-obat yang bekerja menghambat
reseptor 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

41

 BLOKER AGENTS :
- Atenolol
- Carvedilol
- Labetalol
- Metopolol
- Nadolol
- Pindolol
- Propranolol
- Timolol, etc.

42

Adverse Drug Reaction

Impaired/
failure
organ

Multiple
disease state

polypharmacy

compliance

Altered organ
response

Altered drug
concentration

Adverse Drug
Reactions

Homeostatic
regulation
43

OXYGEN CONSUMPTION
ANGINA ATTACK
LONGTERM / UNCONTROLED
MYOCARD INFARCTION
CARDIAC ARREST DEATH

44

CARDIAC ARRHYTHMIAS

ARITMIA CORDI
CORD

45

ARITMIA CORDIS : malfunction of the electrical impuls

impul
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)

46

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
47

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 -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.

48

CLAS Ia : quinidine; procainamide; disopyramide (norpace

CLAS Ib : lidocaine (xylocaine); mexiletine; tocainide

CLAS Ic : flecainide; indecainide; propafenone (rythmonor

moricizine
CLAS II : propranolol; esmolol; sotalol
CLAS III: amiodarone; bretylium; dofetilide; ibutilide
CLAS IV: verapamil; diltiazem
Others : adenosine; digoxin; magnesium sulfate

49

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
50