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CLINICAL PHARMACOLOGY:CARDIOVASCULAIR

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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 .

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HEARTHEARTAs 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 SEORANG ANAK PEREMPUAN 7 TAHUN,DIBAWA ORANG TUANYA UNTUK PERIKSA PADA SAUDARA KARENA ANAKNYA MENDERITA UNTUK PERIKSA PADA SAUDARA KARENA ANAKNYA MENDERITA DEMAM KURANG LEBIH SEMINGGU; MENGELUH SENDI-2 NYA DEMAM KURANG LEBIH SEMINGGU; MENGELUH SENDI-2 NYA NYERI/SAKIT; KEJADIAN INI PERNAH DIALAMI BEBERAPA NYERI/SAKIT; KEJADIAN INI PERNAH DIALAMI BEBERAPA WAKTU YANG LALU; KADANG-KADANG BICARA TAK JELAS; WAKTU YANG LALU; KADANG-KADANG BICARA TAK JELAS; TAK BISA BERGERAK/LEMAH TAK BISA BERGERAK/LEMAH PADA PEMERIKSAAN SUHU 39°C; CHOREA, ERITEMA, ARTHRITIS.PADA PEMERIKSAAN SUHU 39°C; CHOREA, ERITEMA, ARTHRITIS.

UTK KONFIRMASI DILAKUKAN PEMERIKSAAN PENUNJANG :UTK KONFIRMASI DILAKUKAN PEMERIKSAAN PENUNJANG : DARAH RUTINE LENGKAP , KIMIA DARAH, dan EKGDARAH RUTINE LENGKAP , KIMIA DARAH, dan EKG

1.. PROBLEM ?1.. PROBLEM ? 2. OBJEKTIF ?2. OBJEKTIF ? 3. PEMILIHAN TERAPI 3. PEMILIHAN TERAPI NON FARMAKOLOGIK NON FARMAKOLOGIK FARMAKOLOGIKFARMAKOLOGIK 4. PERESEPAN ?4. PERESEPAN ? 5. INFORMASI, INSTRUKSI dan PERINGATAN-2 ?5. INFORMASI, INSTRUKSI dan PERINGATAN-2 ? 6. MONITORING – EVALUASI INTERVENSI ?6. MONITORING – EVALUASI INTERVENSI ?

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HEART DISEASESHEART DISEASES

HYPERTENSION; HYPERTENSION;

CONGESTIVE HEART FAILURE CONGESTIVE HEART FAILURE or DECOMPENSATIO CORDIS;or DECOMPENSATIO CORDIS;

ANGINA PECTORIS ANGINA PECTORIS ( CHEST-PAIN ( CHEST-PAIN

ACUTE MYOCARDIAC INFARCTION);ACUTE MYOCARDIAC INFARCTION);

CARDIAC ARRHYTMIAS.CARDIAC ARRHYTMIAS.

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KELAINAN/PENYAKITKELAINAN/PENYAKITCARDIOVASCULARCARDIOVASCULAR PADA :PADA : NEONATUS ?NEONATUS ?INFANTS ?INFANTS ?CHILDREN ?CHILDREN ?ADOLESCENS ?ADOLESCENS ?

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HYPERTENSIONHYPERTENSION

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Hypertension SBP > 140 mmHg DBP> 85 mmHg

HeartVital 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

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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)

Risk Factors & Disease History

Grade I (mild) Grade II (moderate)

Grade III(severe)

SBP:140-159 160-179 > 180DBP: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

WHO – ISH, 1999

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CARDIOVASCULAR RISK FACTORS;CARDIOVASCULAR RISK FACTORS;

MAYOR RISK FACTORS :MAYOR RISK FACTORS :

• Hypertension (as components of metabolic syndrome)Hypertension (as components of metabolic syndrome)• Cigarette smokingCigarette smoking

• Obesity ( BMI ≥ 30 )Obesity ( BMI ≥ 30 )• Physical inactivityPhysical inactivity

• DyslipidemiaDyslipidemia• Diabetes mellitusDiabetes mellitus

• Microalbuminuria or estimated GFR< 60 ml/minMicroalbuminuria or estimated GFR< 60 ml/min• Age >55 years – men; > 65 years for womenAge >55 years – men; > 65 years for women

• Family history of premature CV diseaseFamily history of premature CV disease

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Complications of hypertension

Brain StrokesTIA (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 When Starting PHARMACOTHERAPEUTICSPHARMACOTHERAPEUTICS• 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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ANTIHYPERTENSIVEANTIHYPERTENSIVE AGENTS (CLASSES)AGENTS (CLASSES)

DIURETICSDIURETICS ββ- BLOCKERS- BLOCKERS ACE-inhibitorsACE-inhibitors CALCIUM CHANNEL BLOCKERSCALCIUM CHANNEL BLOCKERS ARBs (angiotensine receptor blockers)ARBs (angiotensine receptor blockers)

aldosterone receptors antagonistsaldosterone receptors antagonists αα–– adrenoceptor antagonists adrenoceptor antagonists central sympatholytic actionscentral sympatholytic actions arteriolar dilatorsarteriolar dilators peripheral sympathetic inhibitorsperipheral sympathetic inhibitors

INITIAL INITIAL PHARMACOTHERAPYPHARMACOTHERAPY

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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•Renalartery stenosis (bilateral)

- Blocker Prostatic hypertrophy •Glucose intolerance •dyslipidemia

Orthostatic hypotension

Angiotensin IIReceptor antagonist

Ace – inhibitor cough Heart failure •Pregnancy•Hyperkalaemia•Renalartery stenosis (bilateral)

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Choice of initial drugsChoice of initial drugs DiureticsDiuretics

ββ - blockers - blockers Calcium channel blockerCalcium channel blocker

ACE inhibitorACE inhibitor AIIRA / ARBAIIRA / ARB

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Pharmacotherapy hypertension ( in Elderly ) Diuretic

Calcium channel blocker (calcium antagonist)

Dihydropyridines

Non dihydropyridines

Amlodipine 2,5- 10 mgFelodipine 2,5- 20 mgIsradipine 5 - 20 mgNicardipine 60 - 40 mgNifedipine 30 –120 mgNisaldipine 20 – 60 mg

Benzothiazepin (diltiazem) 120 – 360 mgPhenylalkilamine 50 – 100 mg(mibefrazil)Veropamil 90 – 180 mg

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STEP CARE: STEP CARE: RIGIDRIGID VS VS LIBERALLIBERAL

OldOld New approachNew approach

Some variation of :Some variation of :1. 1. Diuretic or Diuretic or ββ--

blockerblocker2. Vasodilatation2. Vasodilatation3. Combination3. Combination

4. Central agents4. Central agents

Evidence based and patient Evidence based and patient guided choiceguided choice

DiureticsDiuretics

ββ - blocker - blockerCCBCCB

ACEIACEI

ARBARB

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Choice of the initial drugsChoice of the initial drugs

Should tailored to the patients, for example Should tailored to the patients, for example in gout do not administered thiazidein gout do not administered thiazide

In asthmatic patients In asthmatic patients do notdo not give beta give beta blocker.blocker.

In “blacks people” ACE inhibitor or In “blacks people” ACE inhibitor or beta-blockers are not very effectivebeta-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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JNC VIIIJNC VIII Pada pasien 60 tahun atau lebih yang tidak memiliki Pada pasien 60 tahun atau lebih yang tidak memiliki diabetes atau penyakit ginjal kronik, maka target terapi diabetes atau penyakit ginjal kronik, maka target terapi tekanan darah sekarang <150/90 mHg.tekanan darah sekarang <150/90 mHg.

Pada pasien 18-59 tahun tanpa kormobiditas mayor, dan Pada pasien 18-59 tahun tanpa kormobiditas mayor, dan pada pasien 60 tahun atau lebih yang memiliki diabetes, pada pasien 60 tahun atau lebih yang memiliki diabetes, penyakit ginjal kronik, atau keduanya, maka target terapi penyakit ginjal kronik, atau keduanya, maka target terapi tekanan darah yang baru adalah <140/90 mmHg.tekanan darah yang baru adalah <140/90 mmHg.

Terapi lini pertama dan selanjutnya sekarang harus Terapi lini pertama dan selanjutnya sekarang harus dibatasi menjadi empat golongan obat: diuretik-tipe dibatasi menjadi empat golongan obat: diuretik-tipe thiazide, thiazide, calcium channel blockercalcium channel blocker (CCB), ACE Inhibitor, (CCB), ACE Inhibitor, dan ARB. dan ARB.

Alternatif lini kedua dan ketiga termasuk dosis yang Alternatif lini kedua dan ketiga termasuk dosis yang lebih tinggi atau kombinasi dari diuretik-tipe thiazide, lebih tinggi atau kombinasi dari diuretik-tipe thiazide, calcium channel blockercalcium channel blocker, ACE Inhibitor, dan ARB. , ACE Inhibitor, dan ARB.

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JNC VIIIJNC VIIIBeberapa obat sekarang didesain sebagai alternatif lini Beberapa obat sekarang didesain sebagai alternatif lini selanjutnya yaitu: selanjutnya yaitu: beta-blockersbeta-blockers, , alphablockersalphablockers, , alpha1/beta-blockersalpha1/beta-blockers (mis. carvedilo), (mis. carvedilo), vasodilating beta-vasodilating beta-blockers blockers (mis. nebivolol), (mis. nebivolol), central alpha2/-adrenergic central alpha2/-adrenergic agonists agonists (mis. clonidine), (mis. clonidine), direct vasodilators direct vasodilators (mis. (mis. hydralazine), hydralazine), loop diuretics loop diuretics (mis. furosemide), (mis. furosemide), aldosterone aldosterone antagoinsts antagoinsts (mis. spironolactone), dan (mis. spironolactone), dan peripherally acting peripherally acting adrenergic antagonists adrenergic antagonists (mis. reserpine). (mis. reserpine).

Saat memulai terapi, pasien keturunan Afrika tanpa Saat memulai terapi, pasien keturunan Afrika tanpa penyakit ginjal kronik harus menggunakan CCB dan penyakit ginjal kronik harus menggunakan CCB dan thiazide daripada ACE Inhibitor.thiazide daripada ACE Inhibitor.

Penggunaan ACE Inhibitor dan ARB direkomendasikan Penggunaan ACE Inhibitor dan ARB direkomendasikan pada seluruh pasien dengan penyakit ginjal kronik tanpa pada seluruh pasien dengan penyakit ginjal kronik tanpa melihat latar belakang etnis, baik sebagai terapi lini pertama melihat latar belakang etnis, baik sebagai terapi lini pertama atau sebagai tambahan pada terapi lini pertama.atau sebagai tambahan pada terapi lini pertama.

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JNC VIIIJNC VIIIACE Inhibitor dan ARB tidak boleh digunakan pada ACE Inhibitor dan ARB tidak boleh digunakan pada pasien yang sama secara bersamaan.pasien yang sama secara bersamaan.

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

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CONGESTIVE HEART FAILURECONGESTIVE HEART FAILURE( C H F )( C H F )

DECOMPENSATIO CORDISDECOMPENSATIO CORDIS

GAGAL JANTUNGGAGAL JANTUNG

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CONGESTIVE HEART FAILUREDECOMPENSATIO CORDISGAGAL JANTUNG

Cardiac output is inadequate to provide Cardiac output is inadequate to provide the oxygen needed by the bodythe 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 FAILURECONGESTIVE HEART FAILURE( C H F )( C H F )DECOMPENSATIO CORDISDECOMPENSATIO CORDISGAGAL JANTUNGGAGAL JANTUNG

CONGESTIVE / CHRONICCONGESTIVE / CHRONIC

ACUTE H F/PULMONARY EDEMAACUTE H F/PULMONARY EDEMA

Increased exertionEmotion

Salt in dietNoncompliance

etc.

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1. CORRECTION THE REVERSIBLE CAUSES;1. CORRECTION THE REVERSIBLE CAUSES;

2. INCREASING MYOCARDIAC CONTRACTILITY;2. INCREASING MYOCARDIAC CONTRACTILITY;

3. REDUCING CARDIAC 3. REDUCING CARDIAC PRELOADPRELOAD (blood volume filling heart ventricle (blood volume filling heart ventricle

during diastolic phase);during diastolic phase);

4. REDUCING CARDIAC 4. REDUCING CARDIAC AFTERLOADAFTERLOAD ( pressure needed for pumping the blood ( pressure needed for pumping the blood

to the circulation systems ;to the circulation systems ;Systolic phase)Systolic phase)

STRATEGY CHF STRATEGY CHF

NON-PHARMACOTHERAPYNON-PHARMACOTHERAPY

PHARMACOTHERAPYPHARMACOTHERAPY

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TREATMENT OF CHRONIC H F :TREATMENT OF CHRONIC H F :

1.1. Reduce workload of the heartReduce workload of the heart a. Limit activity, put on bed resta. Limit activity, put on bed rest

b. Reduce body weightb. Reduce body weight c. Control hypertensionc. Control hypertension

2. Restrict sodium intake2. Restrict sodium intake

3. Restrict water3. Restrict water

4. Give diuretic4. Give diuretic5. Give ACE inhibitor or ARB5. Give ACE inhibitor or ARB

6. Give digitalis6. Give digitalis (if systokic dysfunction with 3(if systokic dysfunction with 3rdrd heart soundor heart soundor

atrial fibrillation present)atrial fibrillation present)

7. Give 7. Give ββ--blockerblocker (to patients with stable class II-IV HF)(to patients with stable class II-IV HF)

8. Give vasodilators8. Give vasodilators

9. Cardiac resynchronization if9. Cardiac resynchronization if wide QRS interval is present in normal sinuswide QRS interval is present in normal sinus

rhythm.rhythm.

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PHARMACOTHERAPYPHARMACOTHERAPY

DIURETICSDIURETICS ALDOSTERONE RECEPTOR ANTAGONISTALDOSTERONE RECEPTOR ANTAGONIST ACE – inhibitorsACE – inhibitors ANGIOTENSIN RECEPTOR BLOCKERSANGIOTENSIN RECEPTOR BLOCKERS BETA – blockersBETA – blockers CARDIAC GLYCOSIDES / CARDIOTONICCARDIAC GLYCOSIDES / CARDIOTONIC VASODILATORSVASODILATORS BETA AGONISTS, dopamineBETA AGONISTS, dopamine BIPYRIDINESBIPYRIDINES NATRIURETIC PEPTIDENATRIURETIC PEPTIDE (Katzung,BG et al., 2007)(Katzung,BG et al., 2007)

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MECHANISM and SITE OF ACTIONMECHANISM and SITE OF ACTIONDRUGS USE IN DRUGS USE IN CONGESTIVE HEART FAILURECONGESTIVE HEART FAILURE

1.1. DIGOXINDIGOXIN (an alkaloid GLYCOSIDE / CARDIOTONIC) (an alkaloid GLYCOSIDE / CARDIOTONIC) increase myocardium contractility by increasing calcium penetration to increase myocardium contractility by increasing calcium penetration to myocardiummyocardium DOBUTAMINEDOBUTAMINE ( SYMPATHOMIMETIC Group ) ( SYMPATHOMIMETIC Group ) increase myocardium contractility by increasing production cAMP in increase myocardium contractility by increasing production cAMP in bounding bounding ββ1 1 -receptor. -receptor. 2.2. DIURETICs GroupDIURETICs Group;; reducing afterload by reducing blood volume ( increase of urine excretion )reducing afterload by reducing blood volume ( increase of urine excretion )

3.3. Angiotensin Converting Enzym (ACE) – Inhibitors / ARBsAngiotensin Converting Enzym (ACE) – Inhibitors / ARBs:: CAPTOPRIL; CANDESARTAN; dll. CAPTOPRIL; CANDESARTAN; dll. the effect dilatation peripheral blood vessels the effect dilatation peripheral blood vessels cause decreasing cause decreasing afterloadafterload

4.4. HYDRALAZINE HYDRALAZINE relaxation of arteriole relaxation of arteriole decreasing afterload decreasing afterload

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HAL-HAL YANG PERLU DIPERHATIKAN PADA HAL-HAL YANG PERLU DIPERHATIKAN PADA PENDERITA GAGAL JANTUNG:PENDERITA GAGAL JANTUNG:

1.1. INTERAKSI DIGOKSININTERAKSI DIGOKSIN dengan dengan - - CALCIUMCALCIUM POTENSIASI DIGOKSIN. POTENSIASI DIGOKSIN.

- - QUINIDIN QUINIDIN ( golongan ANTIARITMIA CORDIS ) ( golongan ANTIARITMIA CORDIS ) kadar DIGOKSIN kadar DIGOKSIN meningkat ( ikatan dengan protein )meningkat ( ikatan dengan protein )

2.2. MAKANAN / NUTRISIMAKANAN / NUTRISI : JANGAN diberikan yang memperberat : JANGAN diberikan yang memperberat

kerja jantung atau yang BERINTERAKSI dengan OBAT-OBAT yang kerja jantung atau yang BERINTERAKSI dengan OBAT-OBAT yang digunakan.digunakan.

3.3. Untuk DIGOKSIN, salah satu sifat obat ini Untuk DIGOKSIN, salah satu sifat obat ini di akumulasi ditubuhdi akumulasi ditubuh, cara, cara pemakaian harus memperhatikan besar obat yang diekresikan dalampemakaian harus memperhatikan besar obat yang diekresikan dalam

24 jam. Waktu paruh panjang ( 40 - >160 jam ). 24 jam. Waktu paruh panjang ( 40 - >160 jam ).

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ANGINA PECTORISANGINA PECTORISCHEST PAINCHEST PAINNYERI DADANYERI DADA

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DRUGS USED IN THE TREATMENTDRUGS USED IN THE TREATMENTOF OF ANGINA PECTORISANGINA PECTORIS..

angina pectoris refers to a strangling or pressure-like pain angina pectoris refers to a strangling or pressure-like pain caused by cardiac ischemia.caused by cardiac ischemia. The pain is usually located sub sternally but sometimes The pain is usually located sub sternally but sometimes perceived in the neck, shoulder, or epigastrium.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= ACUTE CORONARY SYNDROME

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ANGINA PECTORISANGINA PECTORISimpairment oxygenation of the heart muscleimpairment oxygenation of the heart muscle

Imbalancing the supply to the need of oxygen Imbalancing the supply to the need of oxygen of the heart muscles (myocardium)of the heart muscles (myocardium)

CHEST PAIN (left side) and/orCHEST PAIN (left side) and/or DYSPNEA, DYSPNEA,

EPIGASTRIC PAINEPIGASTRIC PAIN

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... major determinant of coronary insufficiency : myocardial fiber tension ( the higher the tension,

the greater the oxygen requirement ).................

MYOCARDIAL OXYGEN REQUIREMENTMYOCARDIAL OXYGEN REQUIREMENT

INTRAMYOCARDIAL FIBER TENSION

DIASTOLIC FACTORS

BLOOD VOLUME VENOUS TONE

SYSTOLIC FACTORS

PERIPHERAL RESISTANCE

HEARTRATE

HEARTFORCE

EJECTIONTIME

+ +

+

+ + +

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STABLE ANGINA

Effortincreasesdemand

Vasospasm may reduce supply

Stenosis prevents

increased 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

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VARIANT ANGINA = vasospastic angina = Prinzmetal’s angina

Vasospasm reduces

supply

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 DIGUNAKANPADA 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. FARMAKOTERAPIFARMAKOTERAPI : : - - GLYSERIL TRINITRAT spray 400 mcg/metered dose,GLYSERIL TRINITRAT spray 400 mcg/metered dose, sublingual, sublingual, diulang tiap 5 menit sampai nyeri hilang/berkurang ataudiulang tiap 5 menit sampai nyeri hilang/berkurang atau - - GLYSERIL TRINITRATE tablet 300 – 600 mcg s.lGLYSERIL TRINITRATE tablet 300 – 600 mcg s.l. diulang tiap. diulang tiap 3-5 menit sampai mencapai dosis max 1.800 mcg atau3-5 menit sampai mencapai dosis max 1.800 mcg atau - - ISOSORBIDE DINITRATE tablet 5 mgISOSORBIDE DINITRATE tablet 5 mg, diberikan s.l.. Diulang , diberikan s.l.. Diulang tiap 5 menit. Maksimum 3 tablet.tiap 5 menit. Maksimum 3 tablet.

HINDARI PEMAKAIAN PREPARAT NITRATE BERSAMA-SAMA DENGANSILDENAFIL (dalam waktu 24 jam) atau TADALAFIL (dalam waktu 5-6 hari)

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CALCIUM CHANNEL-BLOCKING MEDICINESCALCIUM CHANNEL-BLOCKING MEDICINES

DIHYDROPYRIDINE :

amlodipine felodipine nicardipine nifedipine nimodipine

nisoldipine, etc.

NON-DIHYDROPYRIDINE :

bepridil diltiazem verapamil

VASODILATATIONVASODILATATION

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ββ-ADRENOCEPTOR-BLOCKING AGENTS -ADRENOCEPTOR-BLOCKING AGENTS

obat-obat yang bekerja menghambat obat-obat yang bekerja menghambat reseptor reseptor ββ serabut syaraf syaraf simpatis serabut syaraf syaraf simpatis

Pada angina hal-hal yang menguntungkan : Pada angina hal-hal yang menguntungkan : -- menurunkan heart ratemenurunkan heart rate

- tekanan darah turun- tekanan darah turun - kontraktilitas otot jantung turun.- kontraktilitas otot jantung turun.

kebutuhan oksigen otot jantung turun kebutuhan oksigen otot jantung turun

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ββ – BLOKER AGENTS : – BLOKER AGENTS :

- AtenololAtenolol- CarvedilolCarvedilol- LabetalolLabetalol- MetopololMetopolol- NadololNadolol- PindololPindolol

- PropranololPropranolol- Timolol, etc.Timolol, etc.

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Adverse Drug ReactionAdverse Drug Reaction

Impaired/ Impaired/ failure failure

organorganMultiple

disease statepolypharmacy compliance

Altered organ response

Altered drug concentration

Homeostatic regulation

Adverse Drug Reactions

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OXYGEN CONSUMPTIONOXYGEN CONSUMPTION

ANGINA ATTACKANGINA ATTACK

LONGTERM / UNCONTROLEDLONGTERM / UNCONTROLED

MYOCARD INFARCTIONMYOCARD INFARCTION

CARDIAC ARRESTCARDIAC ARREST DEATH DEATH

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CARDIAC ARRHYTHMIASCARDIAC ARRHYTHMIASARITMIA CORDISARITMIA CORDIS

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ARITMIA CORDISARITMIA CORDIS : malfunction of the electrical impuls : malfunction of the electrical impuls conduction in the heart.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 ARITMIA CORDIS CLASSIFICATIONCLASSIFICATION

ARITMIA CORDISARITMIA CORDIS from from ATRIUM :ATRIUM : SINUS BRADYCARDIASINUS BRADYCARDIA SINUS TACHYCARDIASINUS TACHYCARDIA MULTIFOCAL ATRIAL TACHYCARDIAMULTIFOCAL ATRIAL TACHYCARDIA PREMATURE ATRIAL DEPOLARIZATION (PAT)PREMATURE ATRIAL DEPOLARIZATION (PAT) ATRIAL FLUTTERATRIAL FLUTTER ATRIAL FIBRILLATIONATRIAL FIBRILLATION

ARITMIA CORDISARITMIA CORDIS from from VENTRICLE :VENTRICLE : VENTRICULAR TACHYCARDIAVENTRICULAR TACHYCARDIA VENTRICULAR FIBRILLATIONVENTRICULAR FIBRILLATION VENTRICULAR PREMATURE DEPOLARIZATION VENTRICULAR PREMATURE DEPOLARIZATION

ARITMIA CORDIS ARITMIA CORDIS conduction from conduction from AAtrium trium VVentricle:entricle: A – V REENTRYA – V REENTRY W-P-W SYNDROME W-P-W SYNDROME

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PHARMACOTHERAPY PHARMACOTHERAPY ARITMIA CORDISARITMIA CORDIS

CLASSIFICATION : I; II; III; IV dan Unclassified )CLASSIFICATION : I; II; III; IV dan Unclassified ) : :

IaIa : action prolong the action potential duration (APD) and dissociate from : action prolong the action potential duration (APD) and dissociate from the channel with intermediate kinetics;the channel with intermediate kinetics;IbIb : action shorten the APD in some tissue of the heart and dissociate from : action shorten the APD in some tissue of the heart and dissociate from the channel with rapid kinetics;the channel with rapid kinetics;IcIc : action have minimal effect on the APD and dissociate from the channel : action have minimal effect on the APD and dissociate from the channel with slow kinetics;with slow kinetics;

IIII : action is sympatholytic. Drugs with this action reduce : action is sympatholytic. Drugs with this action reduce ββ-adrenergic -adrenergic activity in the heart ;activity in the heart ;

IIIIII : action is manifest by prolongation of the APD. Most action block : action is manifest by prolongation of the APD. Most action block the rapid component of the delayed rectifier potassium current (the rapid component of the delayed rectifier potassium current ( I IKKr r ););

IVIV : action is blockade of the cardiac calcium current. This action slows : action is blockade of the cardiac calcium current. This action slows conduction in region where the action potential upstroke is calcium conduction in region where the action potential upstroke is calcium dependent, eg the sinoatrial and atrioventricular nodes;dependent, eg the sinoatrial and atrioventricular nodes;

OthersOthers : the effect depress ectopic focal of the heart. : the effect depress ectopic focal of the heart.

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CLAS Ia : quinidine; procainamide; disopyramide (norpace)CLAS Ia : quinidine; procainamide; disopyramide (norpace)

CLAS Ib : lidocaine (xylocaine); mexiletine; tocainideCLAS Ib : lidocaine (xylocaine); mexiletine; tocainide

CLAS Ic : flecainide; indecainide; propafenone (rythmonorm);CLAS Ic : flecainide; indecainide; propafenone (rythmonorm); moricizinemoricizine

CLAS II : propranolol; esmolol; sotalolCLAS II : propranolol; esmolol; sotalol

CLAS III: amiodarone; bretylium; dofetilide; ibutilideCLAS III: amiodarone; bretylium; dofetilide; ibutilide

CLAS IV: verapamil; diltiazemCLAS IV: verapamil; diltiazem

Others : adenosine; digoxin; magnesium sulfate Others : adenosine; digoxin; magnesium sulfate

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VASODILATOR

systemic vascularsystemic vascularresistanceresistance

arterial pressurearterial pressureSodium excretionSodium excretion sympathetic nervous sympathetic nervous system outflowsystem outflow

renin releaserenin release

angiotensin IIangiotensin II

arterial blood pressurearterial blood pressuresodium retentionsodium retentionplasma volume plasma volume cardiac outputcardiac output

systemic systemic vascularvascular

resistanceresistance

heart rateheart rate

cardiac cardiac contractillitycontractillity

venous venous capacitancecapacitance

aldosteronaldosteron