Farmakoterapi Jumat, 04 Mei 2018

PENDAHULUAN
 IHD = CAD (coronary artery disease)
 sindrom dengan nyeri di dada akibat terjadinya iskemik pada
miokardium  kebutuhan oksigen miokardium lebih besar
daripada pasokannya
Arief Rahman Hakim  IHD meliputi :
arief.h1@gmail.com  an acute coronary syndrome (ACS, termasuk unstable angina and non–ST-
085729169918 segment elevation or ST-segment elevation myocardial infarction [MI]),
 chronic stable exertional angina (angina pektoris/stabil),
 ischemia due to coronary artery vasospasm (variant or Prinzmetal angina)
 ischemia without symptoms,

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EPIDEMIOLOGI ETIOLOGI
 Faktor resiko yang tidak dapat dimodifikasi
 2400 orang amerika meninggal tiap hari atau 1  Riwayat keluarga : 5% populasi memiliki riwayat CAD

meninggal tiap 33 detik karena CVD
 48% CVD (Cardiovascular disease)  CAD
(Coronary artery disease)
 Insidensi rate = 1,5% (0,1-5 per 1000) tergantung
pada umur pasien, gender, faktor resiko
 Umur : resiko CAD meningkat dengan bertambahnya umur  > 40 th
 fleksibilitas arteri <<
 Jenis kelamin :
 insidensi CAD pada wanita premenopaus lebih rendah daripada pria pada
umur yang sama;
 perbedaan turun pada wanita menopaus;
 setelah umur 65 th insidensi pada wanita lebih tinggi daripada pria

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ETIOLOGI (lanjutan)
Patofisiologi
 Faktor resiko yang dapat dimodifikasi
 Merokok : CAD  2-3x  insidensi aterosklerosis  
pelepasan katekolamin (TD ) dan asam lemak bebas  Kebutuhan oksigen miokard (MVO2)  HR, kontraktilitas,
(HDL  & LDL )  pembentukan “clot” pada arteri  tegangan dinding intramiorkard selama fase sistol
 Hipertensi : TD   arteri mjd kaku dan sempit   Faktor utama kejadian iskemik :
simptom iskemik (tu aktivitas fisik)  Resistensi pembuluh darah yg membawa darah ke miokard
 Hiperlipidemi : kolesterol   CAD   MVO2 yang meningkat
 obesitas
 sedentary lifestyle
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Patogenesis iskemik miokardium

Angina Reversibel
 Angina Stabil (Angina klasik)
 serangan terjadi saat kerja fisik atau emosi
 Derajat nyeri atau ketidaknyamanan tidak mengalami
perubahan selama 60 hari
 Penyebab : aterosklerosis
 Angina varian (Angina Prinzmetal)
 Serangan bisa terjadi selama kondisi istirahat dan
bisa juga di pagi hari
 Penyebab : spasme arteri koroner

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Angina Stabil

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Angina Stabil
Angina Varian

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Faktor pemicu, simptom dan tanda serangan angina

Faktor pemicu, simptom dan tanda serangan angina
 Faktor pemicu  Tanda
 Aktivitas fisik  naik tangga, saat berhubungan badan,
 Rekaman EKG
bersepeda, jogging
 Emosi  HR meningkat
 Selama serangan :
 Angina stabil  depresi segmen ST
 Makan terlalu banyak  perfusi GI meningkat
 Angina varian  elevasi segmen ST
 Cuaca berangin dan dingin  vasokontriksi perifer (resistensi
perifer )  Antara serangan : normal
 Simptom
 Onset : nyeri bisa selama 30 detik atau sampai 30 menit
 Dada terasa sesak
 Hilang bila istirahat atau pemberian obat nitrat
 Nyeri menyebar ke tenggorokan, bahu dan lengan kiri
 Takikardi, berkeringat, gelisah
 Susah bernafas
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Depresi segmen ST Tujuan (outcome) Terapi

 Jangka Pendek:
Elevasi segmen ST
 Menurunkan atau mencegah gejala angina yang membatasi
kemampuan beraktivitas dan mengurangi kualitas hidup
 Jangka Panjang:
 Mencegah kejadian CHD (PJK) spt MI, aritmia, dan HF
 Memperpanjang hidup pasien

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Algoritma terapi IHD Serious contraindication No

Antianginal drug Chest Pain
Intermediate to high probability Education Ad or substitute CCB if no Succesful Yes
treatmet Yes
Of CAD contraindication Treatment?
High risk CAD
Sublingual NTG Serious contraindication No Consider
Revascularization
therapy
History suggests CCB Add long-acting
Vasospastic angina? Yes No
Long acting nitrate therapy Nitrate therapy if no Yes Succesful
(Prinzmetal) contraindication Treatment?

No Yes

Medications or Yes
Treat Yes
Successful
Conditions that provoke Yes Treatment? Condition that exacerbate or provoke angina
appropriately
Or exacerbate angina? Medication : vasodilators, excessive thyroid replacement, vasocontrictors
No Other medical problems : profound anemia, uncontrolled hypertension,
Hyperthyroids, hypoxemia
Yes Other cardiac problems : tachyarrhytmias, bradyarrhytmias, valvular hearth
BB therapy if Yes
Successful
no contraindication Treatment? Disease, hypertrophic cardiomyopathy
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Education and risk

Factor modification

Initiate educational
program
Aspirin 81-325 mg QD Serious
If no contraindication Adverse effect
Or CI
Yes
Cigarette smoking? Yes
Routine follow-up No
Including : diet,
Cholesterol high Yes
Exercise program,
Diabetes management
No
Blood pressure high? Yes
Terapi Angina Stabil
Clopidrogel  Terapi Nitrate  the first step in managing acute
attacks bila episode serangan tidak terlalu sering
(beberapa kali per bulan)
Smoking cessation
program  prophylaxis saat beraktivitas  nitroglycerin 0,3 to 0,4 mg
sublingually 5 menit sebelumnya
 Bila serangan > sekali dalam sehari β-Blockers
See NCEP Guidelines
(e.g., potential cardioprotective effects,
antiarrhythmic effects, lack of tolerance,
See JNC VII Guidelines antihypertensive efficacy)

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Terapi Angina Stabil Terapi Angina Varian

 CCB  meningkatkan coronary blood flow (vasodilation) 
menurunkan MVO2 dan sebagai terapi alternatif pengganti β-
blockers
 long-acting forms of nitroglycerin (oral or transdermal : ISDN,
ISMN)  juga efektif, tetapi terjadinya toleransi  penggunaan
dibatasi
 Nitrates  terapi utama dan kebanyakan pasien
merespon cepat untuk sublingual nitroglycerin atau
ISDN
 Nifedipine, verapamil, and diltiazem  sama
efektifnya sebagai terapi tunggal
 Bila pasien tidak merespon pada terapi CCB 
tambahkan nitrat

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Terapi Angina Varian
 Kombinasi nifedipine+diltiazem atau
nifedipine+verapamil  dilaporkan bermanfaat untuk
pasien unresponsive to single-drug regimens.
 β-Blockers  little or no role in the management of
variant angina  dapat memacu coronary
vasoconstriction and prolong ischemia
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Beta Bloker
 Ideal candidates for β-blockers include patients in
whom physical activity is a prominent cause of attacks;
those with coexisting hypertension, supraventricular
arrhythmias, or post-MI angina; and those with anxiety
associated with anginal episodes
 β-Blockade effective in chronic exertional angina as
monotherapy and in combination with nitrates and/or
calcium channel blockers (CCBs)
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Jumat, 04 Mei 2018
Beta Bloker
 Menurunkan HR, contractility, and blood pressure 
reduce MVo2 and oxygen demand in patients with
angina terpacu aktivitas fisik
 β-Blockers do not improve oxygen supply, dan, pada
kasus tertentu, dapat menstimulasi α-adrenergic may
lead to coronary vasoconstriction
 β-Blockers improve symptoms in approximately 80% of
patients with chronic exertional stable angina
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Beta Bloker
 Initial doses of β-blockers should be at the lower end of
the usual dosing range and titrated to response
 Semua β-blocker  sama efektifnya
 Cardioselective β-blockers digunakan untuk
meminimalkan ESO spt bronchospasm, and sexual
dysfunction.
 ESO  hypotension, heart failure, bradycardia, heart
block, bronchospasm, altered glucose metabolism,
fatigue (kelelahan), malaise (lemas), and depression
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Nitrat
 Sublingual, buccal, or spray nitroglycerin products are
preferred for mengurangi of anginal attacks because of
rapid absorption
 Symptoms may be prevented by prophylactic oral or
transdermal products (usually in combination with β-
blockers or CCBs), but development of tolerance may be
problematic
 Sublingual nitroglycerin, 0.3 to 0.4 mg, relieves pain in
approximately 75% of patients within 3 minutes, with
another 15% becoming pain free in 5 to 15 minutes
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Nitrat
 Nitrates reduce MVo2, venodilation and arterial-arteriolar
dilation  reduction in wall stress from reduced ventricular
volume and pressure
 Pharmacokinetic characteristics common to nitrates include
large first-pass hepatic metabolism, short half-lives (except for
isosorbide mononitrate [ISMN]), large volumes of
distribution, high clearance rates, and large interindividual
variations in plasma concentrations
 Nitrate therapy may be used to terminate an acute anginal
attack, to prevent effort or stress-induced attacks, or for long-
term prophylaxis, usually in combination with β-blockers or
CCB
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Nitrat
 Because both the onset and offset of tolerance to nitrates occur
quickly, one strategy to menghindari tolerance is to provide a
daily nitrate-free interval of 8 to 12 hours
 Combination therapy is generally used in patients with more
frequent symptoms or symptoms that do not respond to β-
blockers alone (nitrates plus β-blockers or CCBs), in patients
intolerant of β-blockers or CCBs, and in patients with vasospasm
leading to decreased supply (nitrates plus CCBs)
 ESO :
 Postural hypotension, reflex tachycardia, headaches and flushing
(dilatasi pembuluh darah dibawah kulit), and occasional nausea.
 Rash (ruam kulit) (especially with transdermal nitroglycerin)
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CCB
 Direct actions include vasodilation of systemic arterioles
and coronary arteries, leading to reduced arterial pressure
and coronary vascular resistance, menurunkan myocardial
contractility and conduction velocity of the sinoatrial (SA)
and atrioventricular (AV) nodes
 Verapamil and diltiazem cause less peripheral
vasodilation than dihydropyridines (nifedipine) but
greater decreases in AV node conduction
 CCB may improve coronary blood flow through areas of
fixed coronary obstruction by inhibiting coronary artery
vasospasm

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CCB
 Good candidates for CCBs include patients with
contraindications or intolerance to β-blockers,
coexisting conduction system disease (except for
verapamil and diltiazem), Prinzmetal angina,
peripheral arterial disease, severe ventricular
dysfunction, and concurrent hypertension
 Amlodipine is probably the CCB of choice in severe
ventricular dysfunction, and the others should be used
with caution if the EF is less than 40%
 ESO :
peripheral edema, constipation, and dizziness (pusing)
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Evaluasi Outcome Terapi

 Subjective measures of drug response include number of painful
episodes, amount of rapid-acting nitroglycerin consumed, and
symptomatic improvement in exercise capacity (ie, longer
duration of exercise or fewer symptoms at the same exercise
level)
 Once patients have been optimized on medical therapy,
symptoms should improve over 2 to 4 weeks and remain stable
until the disease progresses
 If the patient is doing well, no other assessment may be
necessary
 Objective improvement may be assessed by increased exercise
duration and absence of ischemic changes on ECG

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Evaluasi Outcome Terapi

 Monitor for major adverse effects such as headache and
dizziness (pusing) with nitrates; fatigue (kelelahan) and
lassitude (lesu) with β-blockers; and peripheral edema,
constipation, and dizziness with CCBs
 A comprehensive plan includes monitoring of lipid profiles,
fasting plasma glucose, thyroid function tests,
hemoglobin/hematocrit, and electrolytes

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