CLINICAL PHARMACOLOGY:

CARDIOVASCULAR

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-DISTRIBUTION :
OKSIGEN, NUTRIEN,
WATER, ELEKTROLIT, HEART PUMPING : OXYGEN and
NUTRIEN to whole organ
VITAMIN, HORMON,
and tissues
MEDICINES etc,etc.
to our organ and tssues.

CARDIOVASCULAR VESSELS
‘ROAD’ / pipe for distribution
-CARRYING and
Oxygen and Nutrient
-TRANSPORTING : Carbon
dioxyde; metabolism
production, metabolism
residual BLOOD  CARRYING MATERIAL &
- CONTRIBUTOR : immune sys “GARBAGES” from
- TERMOREGULATION the body to out side .

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 As a PUMP: pumping the blood
HEART 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

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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 ?
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 HEART DISEASES

HYPERTENSION;

 CONGESTIVE HEART FAILURE

or DECOMPENSATIO CORDIS;

ANGINA PECTORIS
( CHEST-PAIN 
ACUTE MYOCARDIAC INFARCTION);

 CARDIAC ARRHYTMIAS.

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KELAINAN/PENYAKIT CARDIOVASCULAR
PADA :

NEONATUS ?
INFANTS ?
CHILDREN ?
ADOLESCENS ?

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HYPERTENSION

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 Hypertension
SBP > 140 mmHg
DBP> 85 mmHg

Vital organs
Heart risk

Coronary factors Myocardium

factors • Stroke
• Multi infarct dementia
• Peripheral vascular
CHD LVH disease
• Aortic aneurysm
• Renal failure
Congestive heart failure

Arrhythmia
cordis Sudden death Disability

R. Boedhi Darmojo, 2000, WHO-ISH, 1999 8

 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

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 Management Strategy Assessed The Patient
Risk Profile
Blood Pressure (mm Hg)
Grade I (mild) Grade II Grade III
Risk Factors & Disease (moderate) (severe)
History 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 HIGH RISK HIGH V. HIGH RISK
or Diabetes
IV. Associated Clinical V. HIGH RISK V. HIGH V. HIGH RISK
Condition RISK
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

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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

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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
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ANTIHYPERTENSIVE AGENTS (CLASSES)

 DIURETICS
 β- BLOCKERS INITIAL
 ACE-inhibitors PHARMACOTHERAPY
 CALCIUM CHANNEL BLOCKERS
 ARBs (angiotensine receptor blockers)

 aldosterone receptors antagonists

 α– adrenoceptor antagonists
 central sympatholytic actions
 arteriolar dilators
 peripheral sympathetic inhibitors

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Pharmacotherapy based on : Efficacy, Safety, + Costly (WHO-ISH, 1999)
Class of drug Compelling indication Possible Compelling C.I Possible C.I
indications
Diuretics •Heart Failure Diabetes Out
•ELDERLY
•Systalic hypertension
ß-Blockers • Angina Heart Failure •Asthma & CoPD •Phslipidemia
• After M.I Pregnancy •Heart Block •Athletes, physically active
• Tachyarrhythmia Diabetes (gr 2/3 AV) patients
•Peripheral vascular disease
Calcium •Angina Peripheral Heart block Congestive heart failure
antagonists •ELDERLY vascular disease
•Systolic hypertension
ACE inhibitors •Heart Failure •Pregnancy
•LU Dysfunction •Hyperkalaemia
•After myocardial infarct •Renalartery stenosis
(bilateral)
 - Blocker Prostatic hypertrophy •Glucose Orthostatic hypotension
intolerance
•dyslipidemia
Angiotensin II Ace – inhibitor cough Heart failure •Pregnancy
Receptor •Hyperkalaemia
antagonist •Renalartery stenosis 16
(bilateral)
Choice of initial drugs
 Diuretics
 β - blockers
 Calcium channel blocker
 ACE inhibitor
 AIIRA / ARB

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Pharmacotherapy hypertension ( in
Elderly ) Diuretic

Calcium channel blocker (calcium antagonist)

Amlodipine 2,5- 10 mg
Dihydropyridines Felodipine 2,5- 20 mg
Isradipine 5 - 20 mg
Nicardipine 60 - 40 mg
Nifedipine 30 –120 mg
Nisaldipine 20 – 60 mg

Non dihydropyridines Benzothiazepin (diltiazem) 120 – 360 mg

Phenylalkilamine 50 – 100 mg
(mibefrazil)
Veropamil 90 – 180 mg

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 STEP CARE: RIGID VS LIBERAL

Old New approach

Some variation of : Evidence based and patient

1. Diuretic or β-blocker guided choice
2. Vasodilatation
ARB
3. Combination Diuretics
4. Central agents ACEI
β - blocker
CCB

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 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

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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.
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CONGESTIVE HEART FAILURE
(CHF)

DECOMPENSATIO CORDIS

GAGAL JANTUNG

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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 .

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CONGESTIVE HEART FAILURE
(CHF)
DECOMPENSATIO CORDIS
GAGAL JANTUNG

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

ACUTE H F/PULMONARY EDEMA

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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
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 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 systolic dysfunction with 3rd heart sound or 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
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rhythm.
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)

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 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

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 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 ).

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ANGINA PECTORIS
CHEST PAIN
NYERI DADA

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 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.

 ATHEROSCLEROTIC ANGINA
Type of ANGINA = CLASSIC ANGINA
= ANGINA OF EFFORT

 VASOSPASTIC ANGINA
= REST ANGINA
= VARIANT ANGINA
 UNSTABLE ANGINA = PRINZMETAL’S ANGINA
= CRESCENDO ANGINA
= ACUTE CORONARY SYNDROME
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 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
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 ... major determinant of coronary insufficiency :
myocardial fiber tension ( the higher the tension,
the greater the oxygen requirement ).................

MYOCARDIAL OXYGEN REQUIREMENT

INTRAMYOCARDIAL FIBER TENSION

+
EJECTION
TIME
+ + + + +
HEART
PERIPHERAL HEART FORCE
BLOOD VOLUME VENOUS TONE
RESISTANCE RATE

DIASTOLIC FACTORS SYSTOLIC FACTORS

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 STABLE ANGINA

Vasospasm may
reduce supply

rev ents
o sis p pply Effort
Sten ased su increases
e
in c r 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 34
 VARIANT ANGINA = vasospastic angina = Prinzmetal’s angina

sm r e duces
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.
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 Drugs used in angina pectoris

Vasodilators Cardiac depressants

Nitrates Calcium blockers Beta-blockers

Long duration

Intermediate

Short duration
(Trevor,AJ; Katzung,BG; Masters,SB; 2005)
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 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)

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 CALCIUM CHANNEL-BLOCKING MEDICINES

DIHYDROPYRIDINE : NON-DIHYDROPYRIDINE :

 amlodipine  bepridil
 felodipine  diltiazem
 nicardipine  verapamil
 nifedipine
 nimodipine
 nisoldipine, etc.

VASODILATATION
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 β-ADRENOCEPTOR-BLOCKING AGENTS

 obat-obat yang bekerja menghambat reseptor β serabut syaraf simpatis

Pada angina hal-hal yang menguntungkan :

- menurunkan heart rate
- tekanan darah turun
- kontraktilitas otot jantung turun.

kebutuhan oksigen otot jantung turun

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β – BLOKER AGENTS :

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

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 Adverse Drug Reaction

Impaired/
failure organ Multiple polypharmacy compliance
disease state

Altered organ
response

Adverse Drug
Altered drug
concentration Reactions

Homeostatic
regulation

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 OXYGEN CONSUMPTION

ANGINA ATTACK

LONGTERM / UNCONTROLED

MYOCARD INFARCTION

CARDIAC ARREST  DEATH

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CARDIAC ARRHYTHMIAS
ARITMIA CORDIS

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 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)

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 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

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 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.

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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

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