Basic Overview of Cardiovascular System Physiology and Patient Case Study

CLINICAL PHARMACOLOGY:

CARDIOVASCULAR

2

CARDIOVASCULAR

HEART

VESSELS

BLOOD

-DISTRIBUTION :

OKSIGEN, NUTRIEN, WATER, ELEKTROLIT, VITAMIN, HORMON, MEDICINES etc,etc.

to our organ and tssues.

-CARRYING and

-TRANSPORTING : Carbon dioxyde; metabolism production, metabolism residual

- CONTRIBUTOR : immune sys - TERMOREGULATION

→PUMPING : OXYGEN and NUTRIEN to whole organ and tissues

→‘ROAD’ / pipe for distribution Oxygen and Nutrient

→ 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

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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 ?

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 ?

HYPERTENSION

Hypertension

SBP > 140 mmHg DBP> 85 mmHg

Heart

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Vital organs risk

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

Management Strategy Assessed The Patient Risk Profile

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Blood Pressure (mm Hg)

Risk Factors & Disease History

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 RISK V. HIGH RISK

IV. Associated Clinical Condition

V. HIGH RISK V. HIGH RISK V. HIGH RISK

WHO – ISH, 1999

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

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

→ ACE-inhibitors

→ CALCIUM CHANNEL BLOCKERS

→ ARBs (angiotensine receptor blockers)

→ aldosterone receptors antagonists

→ α– adrenoceptor antagonists

→ central sympatholytic actions → arteriolar dilators

→ peripheral sympathetic inhibitors

INITIAL

PHARMACOTHERAPY

Pharmacotherapy

based on : Efficacy, Safety, + Costly (WHO-ISH, 1999) Class of

drug

Compelling indication

Possible indications

Compelling C.I Possible 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

•Pregnancy

•Hyperkalaemia

•Renal artery stenosis (bilateral)

- Blocker Prostatic hypertrophy •Glucose intolerance

•dyslipidemia

Orthostatic hypotension

Angiotensin II Receptor antagonist

ACE– inhibitor cough Heart failure •Pregnancy

•Hyperkalaemia

•Renal artery stenosis

(bilateral) ¹⁶

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)

Dihydropyridines

Non dihydropyridines

Amlodipine 2,5- 10 mg

Felodipine 2,5- 20 mg

Isradipine 5 - 20 mg

Nicardipine 60 - 40 mg

Nifedipine 30 –120 mg

Nisaldipine 20 – 60 mg

Benzothiazepin (diltiazem) 120 – 360 mg Phenylalkilamine 50 – 100 mg (mibefrazil)

Veropamil 90 – 180 mg

STEP CARE: RIGID VS LIBERAL

Old New approach

Some variation of : 1. Diuretic or β-blocker

2. Vasodilatation 3. Combination 4. Central agents

Evidence based and patient guided choice

Diuretics

β - blocker

CCB

ACEI

ARB

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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

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 ( C H F )

DECOMPENSATIO CORDIS

GAGAL JANTUNG KONGESTIF

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 ( C H F )

DECOMPENSATIO CORDIS GAGAL JANTUNG

CONGESTIVE / CHRONIC

ACUTE H F/PULMONARY EDEMA

▪Increased exertion

▪Emotion

▪Salt in diet

▪Noncompliance etc.

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)

STRATEGY CHF

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 3

^rd

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 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

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

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

→ ATHEROSCLEROTIC ANGINA = CLASSIC ANGINA

= ANGINA OF EFFORT

→ VASOSPASTIC ANGINA

= REST ANGINA

= VARIANT ANGINA

= PRINZMETAL’S ANGINA

→ UNSTABLE ANGINA

= CRESCENDO ANGINA

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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

... major determinant of coronary insufficiency :

myocardial fiber tension (→ the higher the tension, the greater the oxygen requirement )...

MYOCARDIAL OXYGEN REQUIREMENT

INTRAMYOCARDIAL FIBER TENSION

DIASTOLIC FACTORS

BLOOD VOLUME VENOUS TONE

SYSTOLIC FACTORS

PERIPHERAL RESISTANCE

HEART RATE

HEART FORCE

EJECTION

+ +

TIME

+

+ + +

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STABLE ANGINA

Effort increases

demand Vasospasm may

reduce supply

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

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

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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)

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 :

→ amlodipine

→ felodipine

→ nicardipine

→ nifedipine

→ nimodipine

→ nisoldipine, etc.

NON-DIHYDROPYRIDINE :

→ bepridil

→ diltiazem

→ verapamil

VASODILATATION

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.

Adverse Drug Reaction

Impaired/

failure organ

^Multiple

disease state

polypharmacy compliance

Altered organ response

Altered drug concentration

Homeostatic regulation

Adverse Drug

Reactions

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OXYGEN CONSUMPTION

ANGINA ATTACK

LONGTERM / UNCONTROLED

MYOCARD INFARCTION

CARDIAC ARREST → DEATH

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)

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 ( I^Kr );

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.

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

TERIMA KASIH

WASSALAMU'ALAIKUM W W