Surya Abadi K / 0910710121

1. Bagaimana aliran darah koroner terjadi

Note that the main coronary arteries lie on the surface of the heart and smaller arteries then penetrate from the surface
into the cardiac muscle mass. It is almost entirely through these arteries that the heart receives its nutritive blood supply.
Only the inner 1/10 millimeter of the endocardial surface can obtain signicant nutrition directly from the blood inside
the cardiac chambers, so that this source of muscle nutrition is minuscule. The left coronary artery supplies mainly the
anterior and left lateral portions of the left ventricle, whereas the right coronary artery supplies most of the right ventricle
as well as the posterior part of the left ventricle in 80 to 90 per cent of people. Most of the coronary venous blood ow
from the left ventricular muscle returns to the right atrium of the heart by way of the coronary sinuswhich is about 75
per cent of the total coronary blood ow. And most
of the coronary venous blood from the right ventricular muscle returns through small anterior cardiac veins that ow
directly into the right atrium, not by way of the coronary sinus. A very small amount of coronary venous blood also ows
back into the heart through very minute thebesian veins, which empty directly into all chambers of the heart.

2. Faktor neuronal dan humoral apa yang mempengaruhi aliran darah koroner
Blood ow in the coronaries usually is regulated almost exactly in proportion to the need of the cardiac musculature for
oxygen. Normally, about 70 per cent of the oxygen in the coronary arterial blood is removed as the blood ows through
the heart muscle. Because not much oxygen is left, very little additional oxygen can be supplied to the heart musculature
unless the coronary blood ow increases. Fortunately, the coronary blood ow does increase almost in direct proportion
to any additional metabolic consumption of oxygen by the heart
The distribution of parasympathetic (vagal) nerve bers to the ventricular coronary system is not very great. However, the
acetylcholine released by parasympathetic stimulation has a direct effect to dilate the coronary arteries.
There is much more extensive sympathetic innervations of the coronary vessels. In Chapter 60, we see that the
sympathetic transmitter substances norepinephrine and epinephrine can have either vascular constrictor or vascular dilator
effects, depending on the presence or absence of constrictor or dilator receptors in the blood vessel walls. The constrictor
receptors are called alpha receptors and the dilator receptors are called beta receptors. Both alpha and beta receptors
exist in the coronary vessels. In general, the epicardial coronary vessels have a preponderance of alpha receptors, whereas
the intramuscular arteries may have a preponderance of beta receptors. Therefore, sympathetic stimulation can, at least
theoretically, cause slight overall coronary constriction or dilation, but usually constriction. In some people, the alpha
vasoconstrictor effects seem to be disproportionately severe, and these people can have vasospastic myocardial ischemia
during periods of excess sympathetic drive, often with resultant anginal pain.
3. Jelaskan macam angina pectoris
Prinzmetal angina (variant angina) is an atypical form of angina that occurs at rest and is caused by coronary artery
spasm. The responsible mechanisms are not fully understood. Spasm can occur in structurally normal coronary arteries
and may be part of a systemic syndrome of abnormal arterial vasomotor reactivity, which includes migraine headache and
Raynaud phenomenon. Usually, however, it develops in atherosclerotic coronary arteries, often in a portion of a vessel
nearby an atherosclerotic plaque. Whereas coronary artery spasm may contribute to the pathogenesis of an acute
myocardial infarction or to the size of the infarct, it is generally not the principal cause of infarction.
Unstable angina, a variety of chest pain that has a less predictable relationship to exercise than does stable angina and
may occur during rest or sleep, is associated with development of nonocclusive thrombi over atherosclerotic plaques. In
some cases of unstable angina, episodes of chest pain become progressively more frequent and longer in duration over a
3- to 4-day period. Electrocardiographic changes are not characteristic of infarction and serum levels of cardiac-specific
intracellular proteins, such as MB isoform of CK (MB-CK) or cardiac troponins T or I, (evidence of myocardial
necrosis), remain normal. Unstable angina is also termed preinfarction angina, accelerated angina or crescendo
angina. Without pharmacologic or mechanical intervention to open up the coronary narrowing, many patients
with unstable angina progress to myocardial infarction.

Angina Stable
Stable,Atherosclerotic,Classic, due to obstruction of coronaries by atheroma.
Nyeri dan ketidaknyamanan memiliki karakteristik:
Terjadi ketika jantung harus bekerja lebih keras, biasanya selama aktivitas fisik.
Bisa diperkirakan datangnya, setiap episode nyeri memiliki kemiripan, atau cenderung sama
Biasanya berlangsung singkat (5 menit atau kurang)
Menurun atau hilang dengan istirahat atau obat angina.
Terasa seperti kembung atau indigestion
Bisa dirasakan seperti nyeri dada yang menyebar ke lengan, punggung atau tempat lain.
Angina Unstable
Due to spasm and partial obstruction of coronaries
Karakteristik nyeri dan ketidaknyamanan meliputi:
Sering terjadi saat istirahat, ketika tidur di malam hari, atau dengan aktivitas ringan.
Tidak bisa diperkirakan datangnya.
Gejala lebih parah dan lebih lama (sekitar 30 menit) disbanding angina stable.
Biasanya tidak hilang dengan istirahat atau obat angina.
Gejala dapat semakin memburuk.
Merupakan tanda bahwa serangan jantung (AMI) akan segera terjadi.

Angina variant
Vasospastic angina due to Spasm of coronaries
Biasanya terjadi saat istirahat dan selama malam hari atau pagi buta.
Cenderung untuk menjadi parah.
Berkurang dengan obat angina.

4. Buat klarifikasi obat anti angina berdasarkan farmakodinaminya dan jelaskan mekanisme kerjanya
Nitrates & Nitrites
Glutathione S-transferase
Nitroglycerine No.
Guanylyl cyclase and NO activates increase c GMP, causing muscle relaxation.
Nitrates relax all types of smooth muscles vascular or non vascular .
Relax both arteries and veins but more effective on veins.
They have no direct effect on cardiac or skeletal muscles.
NO released stimulate guanylyl cyclase
In platelets causing increase cGMP that decrease platelet aggregation.
Calcium channel blockers
1. They block calcium entry in myocardium causing ;
A) decrease myocardium contractility & myocardium oxygen requirement.
B) decrease heart rate causing decrease in myocardium oxygen requirement.
2. Block calcium entry in vascular smooth muscles (arterioles) causing
a)Decrease in peripheral resistance(after load)------ decrease in oxygen requirement.
b)Relief of coronary spasm.
-Adrenoceptor blocking drugs
They decrease both heart rate & myocardial contractility that decrease in myocardial oxygen requirement at rest & in
exercise so improve exercise tolerance.
Potassium channel openers (Nicorandil )
Activation of potassium channels.
Nitric oxide release.
Arterio & venodilators.

5. Buat klarifikasi obat anti angina berdasarkan indikasi penggunaanya
1- Acute attack : Short acting nitrates or nitritis.
2- Prophylactic therapy : Long acting nitrates.
Calcium channel blockers.
- adrenoceptors blockers.
Potassium channel openers
Combination therapy
Nitrates and -adrenoceptors blockers meningkatkanefektivitas terapi angina stabil kronik
Calcium channel blockers and -adrenoceptor blockers menurunkan reflex takikardi karena ca canal bloker dapat dikurangi oleh
beta bloker
Calcium channel blockers and nitrates bersifat adiktif, dianjurkan untuk pasien angina dengan gagal jantung, AV blok,dll.
Calcium channel blockers, -adrenoceptor blockers, nitrates diberikan jika kombinasi 2 obat tidak berhasil.

6. Jelaskan efek samping penggunaan obat anti angina
Nitrates & Nitrites
Orthostatic hypotension
Throbbing headache
Tachycardia
Facial or cutaneous flushing
Tolerance (Tachyphylaxis)
Salt and water retention
Carcinogenicity
Methaemoglobinemia only with nitrities
Ca Channel Blocker
Sefalgia
Pusing
Hipotensi
Releks takikardi
Flushing
Mual muntah
Edema paru atau perifer
Beta-blocker
Depresi
Pusing
Kelemahan dan Kelelahan ringan
Disfungsi seksual
Gangguan tidur



7. Jelaskan perbedaan farmakokinetik obat anti angina
o Nitrat organik
- mengalami first pass effect jika diberikan secara sublingual
- Ekskresi sebagian besar lewat ginjal
- Kadar puncak 4 menit setelah pemberian sublingual
- Absorbsi : >75%
- Saluran GI: 50-60%
- Salep & pacth: transdermal NTG, diabsorbsi dg lambat
- IV : >90%
- Distribusi: 60%
- Metabolisme: t1/2= 1-4 mnt
- Eliminasi: hati
o Beta blocker
- p.o diabsorbsi dg baik; kapsul sustained-release lambat
- Disfungsi pada renal dan hepar mempengaruhi disposisi dari -bloker
- Beta bloker larut lemak (propanolol, alprenolol, oksprenolol, labetalol dan metoprolol) diabsorbsi baik (90%)
- Beta bloker larut air (sotolol, nadolol, atenolol) kurang baik absorbsinya
o Calcium antagonis
- mudah diabsorbsi pada pemberian po dan sublingual
- Nifedipin, verapamil dan diltiazem mudah larut dalam lemak
- Kalsium blocker yang sering digunakan yang bersifat longer-acting seperti diltiazem dan verapamil, Norvasc, atau
Plendil.
Nifedipine, short-acting forms, dapat meningkatkan adrenaline yang berakibat meningkatkan heart rate, jadi jarang
digunakan

8. Jelaskan kontra indikasi penggunaan obat anti angina
Nitrates are contraindicated in increase intracranial pressure. Nitrates can be used safely in increase of intraocular
pressure (Glucoma).

Kontra indikasi beta blocker
Hipotensi
Bradikardi simptomatis
Blok AV derajat 2-3
Gagal jantung kongestif
Diabetes melitus dengan hipoglikemia
Eksaserbasi asma

Kontra indikasi Ca Blocker
kegagalan fungsi miokard
miokard infark baru/ recent
blok AV total
pasien yang sedang hamil