Rasa tidak enak di dada sebagai akibat dari suatu iskemik miokard tanpa adanya infark Adl penyakit

jantung iskemik berkurangnya pasokan oksigen (adanya aterosklerosis koroner atau spasme arteria koroner) dan menurunnya aliran darah ke dalam miokardium. Dapat berkembang menjadi infark miokard.

 Angina

pectoris is a primary symptom of myocardial ischemia, which is the severe chest pain that occurs when coronary blood flow is inadequate to supply the oxygen required by the heart. Chest pain caused by transient myocardial ischemia due to an imbalance between myocardial oxygen supply and demand.

Myocardial Blood Flow Myocardial O2 Demands

Transient Myocardial ischemia

Severe Chest pain

Angina Pectoris
5

Typical Symptom a heavy strangling or pressure-like pain, sometimes may feel like indigestion, usually located in substernal area or precardium, but sometimes radiating to the left shoulder, left arm, jaw , neck, epigastrium or back.

Merupakan gejala utama iskemia miokard yg terjadi bila tdp ketidakseimbangan antara suplai O2 ke jtg dgn kebutuhan O2 jtg

Terjadi penumpukan asam laktat timbul nyeri yang khas dgn gejala berupa: Serangan nyeri hebat di bawah tulang dada yang menjalar ke pundak, leher, rahang atau lengan kiri atas

Serangan berkisar antara 5 10

Types of Angina
1. Stable Angina.

2. Unstable Angina.
3. Variant Angina.
9

ANGINA KLASIK = ANGINA STABIL KRONIK = ANGINA OF EFFORT serangan timbul pada waktu penderita sedang melakukan kerja fisik. PENYEBAB : aterosklerosis dan spasme stress / emosi exposure udara dingin iskemia jtg dg anemia

Angina klasik (angina stabil kronik), terjadi karena adanya aterosklerosis koroner dan timbul gejalanya setelah kerja fisik, emosi atau makan; Is caused by narrowed arteries due to atherosclerosis Occurs when the heart works harder Usually lasts a short time Is relieved by a rest or angina medicine

Angina tidak stabil, ditandai meningkatnya frekuensi dan lama serangan angina, terjadi baik waktu istirahat maupun kerja fisik. Biasanya angina tidak stabil akan cepat berkembang menjadi infark miokard apabila tidak ditangani secara serius dan tepat. Often occurs at rest Is more severe and lasts longer than stable angina Episodes of pain tend to be changing in the character, frequency, duration as well as precipitating factors Is caused by episodes of increased coronary artery tone or small platelet clots occurring in the vicinity of an atherosclerotic plaque.

Merupakan tipe angina pectoris yg dapat berubah menjadi infark miokard ataupun kematian. Telah lama dikenal sebagai gejala awal dari infark miokard akut (IMA) risiko terjadinya IMA dan kematian. 60-70% penderita IMA dan 60% penderita mati mendadak pada riwayat penyakitnya yang mengalami gejala angina pectoris tidak stabil. IMA terjadi pada 5-20% penderita angina pectoris tidak stabil dengan tingkat kematian 14-80%.

Angina varian (Prinzmetal), terjadi karena adanya vasospasem koroner yang dipacu oleh rangsangan pada reseptor 1 dan biasanya gejala timbul pada waktu istirahat Timbul pada waktu istirahat antara tengah malam dan pagi buta. Penyebab : spasme koroner Usually occurs at rest Tend to be severe Is relieved by angina medicine (vasodilators) Is caused by a transient spasm in a coronary artery

Angina variant adalah angina yang diakibatkan kejang sementara arteri jantung di mana serangan nyeri timbul spontan dalam keadaan istirahat dan kebanyakan di malam hari. Angina timbul apabila terjadi ketidakseimbangan antara suplai oksigen dengan kebutuhan oksigen miokardium. Gangguan timbul disebabkan oleh :

Suplai menurun adanya arteriosklerosis koroner atau spasme arteria koroner Kebutuhan meningkat kerja fisik

Variant Angina . (Prinzmetal)

Chest pain at rest due to coronary artery spasm ECG changes:
With chest pain , marked ST segment elevation Return of the ST segment to the baseline after nitroglycerin administration

The baseline ECG

Acute elevation of ST segment

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 An imbalance between the myocardial

oxygen supply and demand.

O2 demand

>

O2 supply

Pathophysiology
Contractility Heart rate Wall tension
O2

The difference of Arteriovenous oxygen pressure

demand

>

O2

supply
Coronary blood flow

Angina
Coronary Vascular resistance

Ventricular Pressure

Ventricular Volume

the duration of diastole

Aortic Diastolic pressure

The underlying cause is

Fissuring of atheroscelerotic plaques Platelet aggregation Thrombosis

Coronary artery spasm

Atheroscelerotic changes
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Management of Angina
Management of Stable Angina
Management of Unstable Angina

Management of Variant Angina

21

Management of Stable Angina

1- General measures. 2- Drug Treatment. 3- Coronary artery
revascularization.
22

General measures
Treat Hypertension , Hypercholestrolimia and Diabetes Stop smoking Reduce weight

AVOID Severe exertion

Heavy meal

Emotions

Cold Weather

Graduated exercise may open new collaterals

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a. For an acute attack b. For immediate pre-exertional prophylaxis c. For long-term prophylaxis d. Antiplatelet therapy.

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Treatment of an acute attack of angina

Sublingual nitroglycerin (0.5 mg ) or isosorbide dinitrate (5 mg ) or Oral spray nitroglycerin (0.4 mg/metered dose), isosorbide dinitrate(1.25 mg/metered dose)
Relief within 1-3 min. Persistence of pain
Repeat nitroglycerin at 5 min. interval (3 tab. max.)

Relief HOSPITALIZATION

not relieved

Infarction
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Immediate pre-exertional prophylaxis of Angina Sublingual nitroglycerin (0.5 mg) or isorbide dinitrate (5 mg) should be taken 5 min. before effort. For Long term prophylaxis: Long acting nitrates, Ca++ channel blockers, b-blockers or combinations of these drugs. Antiplatelet therapy: Aspirin in small dose (75-150 mg daily orally) or Dipyridamole (75 mg t.d.s orally)
26

Coronary artery bypass grafting (CABG) Percutaneous Transluminal coronary Angioplasty (PTCA) For patients not responding to adequate medical therapy

27

Management of Unstable Angina

Nitrate + b-blocker + Aspirin (low dose) and/or Heparin or Thrombolytic (stryptokinase) to minimize risk of infarction

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Management of Variant Angina

Nitrates and/or Ca++ Channel blockers For the acute attack & prophylaxis
29

 Lifestyle changes

Nitrates
Medication

-blockers Calcium channel blockers

Surgery : CABG ( coronary artery bypass graft)

PTCA (percutaneous transluminal coronary angioplasty)

What are the antianginal drugs?

Organic nitrates.
b- adrenoceptor blockers.

Calcium channel blockers.

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NITRATES Relaxation of smooth muscles Dilatation Veins

Arteries
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Cellular Mechanism of Vasodilatation

Nitrates Formation of Nitric oxide (NO)

Synthesis of cyclic GMP

Activation of Guanylate cyclase

Relaxation of Vascular smooth muscles

N.B. (-SH) groups are required for formation of NO.

34

Effect of Nitrates :

On Stable Angina :
1- Venodilatation Preload Arteriolar dilatation Afterload

Myocardial Oxygen demand

2- Redistribution of coronary flow towards subendocardium 3- Dilatation of coronary collateral vessels.

On Variant Angina :
Relax smooth muscles of the epicardial coronaries relieve coronary artery spasm

On Unstable Angina :
Dilatation of epicardial coronary arteries + reducing O2 demands
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Preparations :
For acute attacks Nitroglycerin (sublingual, buccal spray) Isosorbide dinitrate(sublingual, buccal spray)

Short acting

For antianginal prophylaxis Nitroglycerin oral SR (6.25-12mg) 2-4 times/day - 2% ointment (1-1.5 inch/4hrs) - patches (1 patch=25mg)/day

Long acting

Isosorbide dinitrate (oral) 1040mg t.d.s. Isosorbide mononitrate (oral) 20mg/12 hrs.

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Duration of Action of Various Preparations of Organic Nitrates

Preparation
" Short-acting"
1-Nitroglycerin 2- Isosorbide dinitrate a) S ublingual b) S pray a) S ublingual b) S pray a) Oral; sustained release b) Ointment c) Transdermal patches Oral Oral 10-30 min 10-30 min Up to 60 min. 1.5 hours 4-8 hours 3-6 hours 8-12 hours 4-6 hours 6-10 hours

Duration of action

" Long-acting"
1-Nitroglycerin 2- Isosorbide dinitrate 3-Isosorbide mononitrate

Adverse Reactions :
1- Postural Hypotension & Syncope 2- Tachycardia

3- Drug Rash

4- Facial Flushing

6- Prolonged high dose Methaemoglobinaemia

5- Throbbing Headache
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b-blockers are effective in STABLE & UNSTABLE angina

In contrast they are not useful for vasospastic angina (Variant) {Prinzmetal}&

may worsen the condition. This deleterious

effect is likely due to an increase in coronary resistance caused by the unopposed effects of catecholamines acting at a-adrenoceptors.

Mechanism of antianginal action:

The effectiveness of b-adrenoceptor blockers in the treatment of exertional angina is attributable to a fall in myocardial O2 requirement at rest & during exertion due to :
1- A -ve chronotropic effect (particularly during exercise). 2- A -ve inotropic effect.

3- A reduction in arterial blood pressure (particularly

systolic pressure) during exercise.
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Undesirable effects of b-blockers in treatment of angina:

Rate & contractility Systolic ejection period & left ventricular end diastolic vol. Myocardial O2 requirements

However the net effect of b-blockers is to myocardial O2 requirement particularly during exercise; their potentially deleterious effects can be balanced by concomitant use of nitrates
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Dosage and Route of Administration

Drug
Propranolol
Nadolol

Route
Oral
Oral

Dosage
30-360 mg/day in 2-4 divided doses
40-80 mg ONCE daily

Atenolol
Metoprolol

Oral
Oral

50-100 mg ONCE daily

50-100 mg TWICE daily

Adverse Reactions :

CHF

A-V block

Bronchospasm

Cold extremities

Worsening symptoms of PVD

Hypotension
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Adverse Reactions :

Fatigue & weakness

Mask signs of Hypoglycemi a

Nightmares , Hallucinations , Depression.

Plasma Triglycerides & HDL Cholesterol

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Discontinuation after long ttt exacerbates Angina

Contraindications :

CHF

A-V block

Bronchial asthma

Peripheral Vascular disease

Hypotension
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Used in treatment of all types of angina.

Verapamil (80-160 mg) /8 hr Diltiazem (60-120 mg) /8 hr Dihydropyridine group Nifedipine (10-40mg) /8 hr Amlodipine 5mg/day

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Block Voltage -dependent calcium channels (L-type) in cardiac and smooth muscles.
C A L CI U M

Mechanism of anti-anginal action :

1 - Coronary artery dilatation and relief of coronary spasm (variant angina)

2 -Decrease myocardial O2 demand due to: Arteriolar Vascular dilatation resistanc e (Verapamil & Diltiazem) Decrease HR. Decrease contractility Decrease AV conductivity

Afterload

Dosage and Route of Administration

Drug
Verapamil Nifedipine Diltiazem

Route
Oral Oral Oral

Dosage
80-160 mg every 8 hours 10-40 mg every 8 hours 60-120 mg every 8 hours

Adverse reactions :

Dizziness

Ankle edema

Headache

Hypotension

Flushing

Constipation A-V block & HF only with Verapamil & Diltiazem

Reflex Tachycardia with Nifedipine

Contraindications of Verapamil & Diltiazem:

1 - HF

2 - Sinus or A-V node disease.

3 - Bradycardia.

? ?

? ?

b-blockers block reflex tachycardia produced by nitrates Nitrates attenuate the increased left ventricular end-diastolic volume associated with b-blockers

b-blockers decrease reflex tachycardia produced by nifedepine.

Verapamil or Diltiazem decrease tachycardia produced by nitrates.

In patients with stable angina not controlled by two types of antianginal drugs the use of three agents may provide improvement.

I.

NITRAT ORGANIK
MK : otot polos NO reaktif ( radikal bebas )

Nirat organik

guanilat siklase

GMP

c GMP

Defosforilasi miosin

Relaksasi otot polos

Nitrat organik tidak memberikan efek langsung pada jantung

Sediaan : 1. NO3 kerja singkat ex : - gliseril trinitrat sublingual or spray yg mpy durasi 30 menit. - gliserol trinitrat transdermal yg brp plester dgn durasi 24 jam.

2. NO3 kerja lama lebih stabil dan efektif ex : isosorbid dinitrat oral Warning NO3 : Nitrat organik +Vasodilator lain hipotensi -hidralazin -prazosin -nifedipin

II. Beta bloker

digunakan untuk profilaksis pektoris akibat kerja fisik.

angina

MK : menghambat reseptor beta, shg menurunkan frek.denyut jtg & kontraktilitas miokard, shg kebutuhan oksigen miokard juga akan berkurang.

Sediaan : 1. Kardioprotektif beta bloker :

- Propranolol - Timolol - Metoprolol*

2. Kardioselektif beta bloker :

- Atenolol - Asebutalol - Metoprolol

III. Ca Antagonis
MK : Menghambat masuknya ion Ca ekstraselluler pada membran sel jantung dan otot polos Menimbulkan efek lgs inotropik dan kronotropik negatif dan memperlambat konduksi AV

Vasodilatasi Sediaan : - Nifedipin - Verapamil - Diltiazem

Pada Angina tidak stabil, kemungkinan resiko Infark miokard akan meningkat, maka terapinya : 1.NO3 + Beta bloker. 2.Antiplatelet : aspirin 3.Antikoagulan : heparin

TERIMAKASIH