Anti Angina

Noor Wijayahadi
 Tujuan Pembelajaran:
Mampu menjelaskan:
1. Prinsip terapi obat anti angina
2. Kategori jenis obat anti angina
3. Farmakokinetik obat anti angina golongan nitrat
4. Farmakodinamik obat anti angina golongan nitrat
5. Menentukan bentuk terapi terpilih anti angina
berdasarkan ilustrasi kasus
 SUPPLY vs DEMAND
Kurangnya aliran darah jantung akibat
ketidak seimbangan antara suplai oksigen
dan kebutuhan oksigen

Etiologi:
Suplai darah menurun ( aterosklerosis/spasme)
Kebutuhan meningkat ( kerja fisik)
 Angina Pectoris
Angina Pectoris adalah sensasi tidak nyaman pada dada
(strangling in the chest) dan struktur anatomis di sekitarnya
disebabkan oleh iskemik miokard.
Spektrum klinisnya dapat berupa:
1. Angina stabil
Tipe kronik, dipicu oleh aktifitas fisik dan emosi, berkurang
dengan istirahat (Angina of effort)
2. Angina tidak stabil (Klinis sindroma koroner akut:
UAP, NSTEMI, STEMI)
Angina stabil yang frekuensi dan durasi iskemiknya
meningkat dengan aktifitas ringan bahkan saat istirahat,
3. Angina spastik (Variant, Prinzmetal)
Angina yang disebabkan oleh spasmus arteri koronaria.
 Normal Endothelial cell
Angina stabil
Plaque

Patent lumen Lumen narrowed )

Lumen Endothelial function N Vasoconstriction +
Lumen
Lumen

Angina tidak stabil Angina spastik

Platelets
Thrombus No plaque
Lumen Intense vasospasm
Lumen Plaque rupture
Platelet aggregation
Thrombus +
Vasoconstriction +
 Overview
oxygen requirement 
imbalance
oxygen supply 

• Primary cause of angina pectoris:

– In classic angina, the imbalance occurs when
the myocardial oxygen requirement increases;
“angina of effort”
– In variant angina, oxygen delivery decreases as
a result of reversible coronary vasospasm.
“vasospastic or Prinzmetal's angina”
 Factors affecting myocardial oxygen demand
and oxygen supply
Regional
Contractile myocardial
state distribution

Heart Oxygen Oxygen Coronary

rate demand = supply vascular
Ventricular > resistance
volume

Wall
tension Coronary
blood flow
LV Aortic
pressure pressure
afterload preload
 MANIFESTASI KLINIS
Aliran darah ke otot jantung
berkurang (iskemia)

Angina (nyeri dada)

 Types of Angina

• Angina occurs in three

overlapping patterns:
– Stable angina
– Unstable angina
– Prinzmetal (variant)
angina
Vasospasm at rest or during sleep

If the frequency and severity

increases- forerunner to a MI

If symptoms remains the

same and angina occurs
under similar circumstances
 Stable Angina
Angina indicates that myocardial
oxygen demand is exceeding
supply.
“Stable” indicates the reproducible
nature of the angina; the same
activity at the same intensity
faithfully produces symptoms.
Typically this type of angina is
relieved by rest or acute use of
nitroglycerin.
 Unstable Angina
Unstable angina occurs
when anginal symptoms
occur with less cardiac
demand;
These episodes are less or
un-responsive to
nitroglycerine or rest.
Crescendo angina
describes a rapid
progression of
myocardial ischemia
often heralding infarction.
 Prinzmetal (Variant) Angina
This is a relatively uncommon pattern of myocardial ischemia
usually occurring at rest and often in young individuals
(particularly women) lacking classic risk factors or significant
demonstrable coronary disease.
The anginal attacks in PVA tend to have a circadian rhythm and
generally occur in the early morning hours.
These attacks can be triggered by alcohol, drinking iced drinks,
rapid eye movement sleep, ergonovine, atrial pacing, cocaine,
nicotine, acetylcholine, and hyperventilation.
It is induced by coronary artery vasospasm it generally responds
promptly to vasodilators. PVA has been associated with other
vasospastic disorders such as migraine headaches and
Raynaud’s phenomena. Endothelial dysfunction has been
considered as primarily responsible for PVA.
The risk of both ventricular & bradyarrthymias is markedly
increased during spastic events, sudden cardiac death is not
uncommon.
 TUJUAN TERAPI

1.Mengatasi & mencegah

serangan akut
2.Pencegahan jangka panjang
serangan angina (Sindroma
Koroner Akut & Kematian)
3.Meningkatkan toleransi pasien
terhadap latihan
 Overview
Myocardial oxygen demand is diminished by:
• Reducing contractility
• Reducing heart rate
• Reducing the preload
Wall tension 
• Reducing the afterload

Myocardial oxygen supply is increased by:

• Dilating conduct coronary arteries
(  coronary blood flow)
• Promoting regional distribution
(  in ischemic regions)

Treatments:
• Non-drug treatment:(percutaneous
transluminal coronary angioplasty, PTCA), ( coronary artery bypass
graft surgery, CABG )
• Drug treatment
 Antianginal Drugs
Effects of antianginal drugs:
• Reducing oxygen demands
• Increasing oxygen supply
• Others: Anti- platelet coagulation and
thrombus formation

Antianginal drugs:
• Organic nitrates
•  receptor blockers
• Calcium channel blockers
• Anti-platelet agents
• ACEIs
• Fish oil
 ANTIANGINAL (CORONARY
ACTIVE) DRUGS

І. Nitrates and sidnonims which are close to the

first ones
ІІ. Bets-adrenoblockers
ІІІ. Antagonists of calcium ions
ІV. Activators of potassium channels

• Inhibitors of ATE
• Antiaggregants and anticoagulants
• Drugs with metabolic influence on miocardium
 ANTI ANGINA
• 1.Nitrat organik
• 2.β Bloker
• 3.Antagonis kalsium
 VASODILATOR

Obat yang menyebabkan vasodilatasi

Vaskuler
Vasodilator terdiri dari :
1.Venodilator
2.Arteriodilator
3.Arteriovenodilator
 KLASIFIKASI VASODILATOR
Berdasarkan jangka waktu penggunaan :
1.Vasodilator parenteral
Ex: Na-nitropruside & nitrogliserin iv
Digunakan dalam jangka pendek pada
keadaan akut.
2.Vasodilator oral
Ex: Isosorbid dinitrat , ACE inhibitor
Digunakan dalam jangka panjang pada
keadaan kronik.
 Farmakodinamik Nitrat (1)
Endo Cytoplasm
Isosorbide
dinitrate Sarcolemma
Isosorbide
mononitrate Peroxynitrite
GTP
LIVER Physiologic
dilators 
NO
Cyclic
GMP
Mononitrate
R-ONO2 Nitrosothiols

ONO2 Lowers
SH
Nitroglycerin ONO2 NO2 Ca2+
ONO2
ONO2
EXCESS NITRATES VASO-
SH DILATION
• Deplete SH
• Peroxynitrite
Nitrate tolerance Opie (2001)

Effects of nitrates in generating NO and stimulating guanylate

cyclase to cause vasodilation.
 1.NITRAT ORGANIK

Mekanisme kerja 
Radikal bebas NO menstimulasi
guanilat siklase

Kadar C GMP
Defosforilasi miosin
Relaksasi otot polos
KLASIFIKASI NITRAT ORGANIK
1.Nitrat kerja singkat
• a.Sediaan sublingual
Ex:Isosorbid
dinitrat(ISDN)
• b.Amilnitrit inhalasi
2.Nitrat kerja lama
• a.Sediaan oral (biasa &
lepas lambat)
• b.Nitrogliserin topikal
• c.Nitrogliserin
transmukosal
3.Nitrogliserin infus intra vena
 EFEK SAMPING
Sakit kepala, pusing,takikardi,
rasa lemah, dll.
Perhatian /hati hati pada :
• 1.Peningkatan TIK
• 2.Hipotensi berat
• 3.Hipovolemia yang belum diatasi
• 4.kardiomiopati hipertofik
• 5.Stenosis aorta & takiaritmia
 2.β BLOKER
1.Mengurangi kebutuhan oksigen miokard
dengan mengurangfrekuensi,kontraktilitas
dan tekanan darah.
2.Mengurangi suplai oksigen miokard dengan
mengurangi tegangan dinding ventrikel
 β BLOKER
• Propranolol  tidak selektif
• Asebutolol
• Metoprolol
• Atenolol Kardioselektif
• Bisoprolol relatif
 β Bloker
Efek samping :
• Bradikardi, blok AV, bronkospasme
• Keluhan saluran cerna, reaksi alergi dll
Perhatian :
• 1.Penyakit paru obstrktif
• 2.DM yang cendrung mengalami
• hipoglikemia
• 3.Gangguan konduksi jantung
 3.ANTAGONIS KALSIUM
• = Calcium chanel blocker
• Menghambat masuknya ion kalsium melalui
Slow channel pada membran sel.

• Kronotropik(denyut jantung) & inotropik

(kontraksi otot jantung)negatif
• Sediaan : verapamil, diltiazem,amlodipin
• Efek samping : vasodilatasi berlebihan
 ANTAGONIS KALSIUM
Perhatian :
• Bioavailabilitas oral rendah
• Kadar puncak cepat dicapai  TD turun cepat
• T ½ yang pendek
• Metabolisme sempurna oleh hati
• Digunakan bila ada kontra indikasi terhadap
β bloker
 Usage of calcium ions antagonists
Illness Drugs

Hypertension Verapamil Dylthiazem Nifedipin Felodipin Amlodipin

Stenocardia Verapamil Dylthiazem Nifedipin Amlodipin

Supraventric Verapamil Dylthiazem

ular tachy-
arrhythmia

Possible Dylthiazem Nifedipin Felodipin Amlodipin

combination with
β-blockers

-recommended drug --should be used carefully

 Nitroglycerine
Unique transdermal system in a form of plaster
 SINDROM KORONER AKUT

Suatu sindrom yang terdiri dari beberapa

PJK,yaitu:
• angina tak stabil (unstable angina),
• infark miokard non-elevasi ST,
• infark miokard dengan elevasi ST,
• angina pektoris pasca infark atau
• pasca tindakan intervensi koroner
perkutan.
 TERAPI SKA
• 1.Oksigenasi
• 2.Nitrogliserin sublingual
• (0,3-0,6 mg/ aeosol/spray
• Nyeri dada menetap 
• NTG 3 x tiap 5mnt
• Lanjutkan drip intra vena
• Syarat pemberian :TD sistolik >100mmHg
•
 TERAPI SKA
3.Morfin 2-4 mg intra vena
• Mengurangi kecemasan / kegelisahan;
• Mengurangi rasa sakit akibat iskemia
Meningkatkan venous capacitance
Menurunkan tahanan pembuluh
sistemik
Menurunkan nadi dan tekanan darah
 TERAPI SKA
4.ASPIRIN
Menghambat siklooksigenase –1
dalam platelet dan mencegah
pembentukan tromboksan-A2.) .
Kontra indikasi : Ulkus gaster
Asma bronkial
 TERAPI SKA
5.Anti trombotik lain Klopidogrel
Menghambat agregasi platelet,
Memperpanjang waktu perdarahan,
Menurunkan viskositas darah dengan
cara menghambat aksi ADP pada
reseptor platelet.
 TERAPI SKA
• Pertimbangan pemakaian
Klopidogrel Resiko Perdarahan
Didapatkan setiap 1.000 pasien SKA
yang diberikan Klopidogrel, 6 orang
membutuhkan tranfusi darah.