KULIAH TAMU

FARMAKOTERAPI PENYAKIT JANTUNG KORONER

SUHARJONO
Shj_ms_id@yahoo.com
 DEFINISI
• ATHEROSCLEROSIS adalah penumpukan lemak di
bagian intima arteri, yang awalnya lunak dan
mengeras bila lama

• ARTERY DISEASE (CAD-CORONARY ARTERY DISEASE)

adalah tipe kelainan pembuluh darah karena adanya
atherosclerosis

• ACUTE CORONARY SYNDROME (ACS) adalah

keadaan klinik yamg ditandai dengan adanya oklusi
arteri coroner. Ada tiga ACS meliputI angina unstable,
non-ST segmen elevasi MI dan ST-segmen elevasi MI
atau sudden death
Normal Coronary Artery
• LAYERS:
• Tunica Adventia (outer
coat) ,
• Tunica Media ( muscle
coat),
• Tunica Intima ( lining)
Pembuluh Darah Koroner
Pembuluh Darah Koroner Berfungsi :
Memberi makan dan Oksigen ke otot- otot Jantung.

Terdiri Dari:
1. Pembuluh Darah Koroner Kiri , cabang :
kedepan : LAD ( Left Anterior Descendens Artery)
melingkar ke kiri : LCx ( Left Circumflex Artery)
2. Pembuluh Darah Koroner Kanan
( RCA = Right Coronary Artery)

Bercabang-cabang  ke dalam otot-otot jantung

 Serangan Jantung

Kematian sebagian otot jantung disebabkan

oleh terhentinya pasokan darah akibat
tersumbatnya satu / lebih pembuluh koroner
oleh gumpalan darah (trombus).

Akibat Serangan jantung

Fungsi pompa jantung ( memompakan darah

dgn segala nutrisi )  gagal
 Penyakit Jantung koroner

Angina Pektoris Stabil

Angina Pektoris Tidak Stabil

Iskemia Otot Jantung

Infark Miokard Serangan Jantung

INFARK JANTUNG
Myocardial infarct
 Serangan jantung sering kali terjadi antara
pukul 4 - 10 pagi, karena:

jumlah adrenalin lebih tinggi dikeluarkan oleh

kelenjar adrenal

dpt menyebabkan pecahnya lesi aterosklerosis.

 Untaian proses aterosklerosis

Normal Pembentukan sel Ruptur / bocor Trombus/ters

busa umbat

Komposisi plak dan sumbatan: LDL-C, sel2 radang dan bekuan darah ( trombus )
 PROSES PERKEMBANGAN ATEROSKLEROSIS

24
(Schaefer, 2010)
Diagnosis ditegakkan, bila:
( 2 dari 3 indikator )
kriteria WHO terpenuhi, yaitu

• Keluhan klinis
• Gambaran khas elektrokardiografi (EKG)
• Peningkatan kadar enzim jantung :
(CK, CKMB dan troponin)
 TES DIAGNOSTIK (LAB & KLINIK)
1. Electrocardiogram (ECG)
2. Exercise Tolerance Testing
Test toleransi/treadmill
Dapat dikombinasi dengan test perfusi miokardial dg Thallium
(201Tl) utk reversible/ireversible aliran darah jantung
3. Cardiac Imaging
Test radionukleid angiografi (techtenium-99m) mengukur EF (ejection fraction)
4. Echocardiography
Pharmacologic stress echocardiography (dobutamine, dipyridamole or
adenosine) or pacing may be done to identify abnormalities during stress
5. Cardiac Catheterization & Coronary Arteriography
TERAPI PADA PENYAKIT JANTUNG
KORONER

(Libby, 2005)

30
 Treatments

Non Pharmacology Therapy

Revascularization
- Percutaneous Coronary Intervension (PCI) –
Percutaneous Transluminal Coronary Angioplasty
(PTCA)
- Coronary Artery Bypass Grafting (CABG)
Treatments
Based on document prepared by Clopidogrel Guidelines Working Group for Anglia Cardiac Network
May 2006
 Platelet
activation
&
receptors
involved
 Tinjauan Aspirin
• Irreversibly acetylates cyclooxygenase and inhibiting COX-1,
aspirin interferes with the synthesis of prothrombotic TXA2,
important in the platelet activation cycle.
• Dosing:
– PCI: Oral: Initial: 75-325 mg (300-325 mg in aspirin native patients) starting
at least 2 hours (preferably 24 hours) before procedure; post procedure:
162-325 mg once daily (dose and duration varies with type of stent
implanted); Note: Dose may be reduced to 75-162 mg once daily after
appropriate duration based on stent-type is complete

Opie et al, 2012. Drug for the Heart. 8th Ed

Lacy et al, 2009. Drug Information Handbook. 17th Ed
 Tinjauan Clopidogrel
• Inhibitor of the platelet ADP receptor P2Y12 and preventing the
transformation and activation of the GpIIb/IIIa receptor.

• Dosing
– ST-segment elevation myocardial infarction (STEMI): 75 mg once daily (in
combination with aspirin 75-162 mg/day). CLARITY used a 300 mg loading
dose of clopidogrel (with thrombolysis). The duration of therapy was <28
days (usually until hospital discharge) (Sabatine, 2005).
– The American College of Chest Physicians (Goodman, 2008) recommends:
Patients <75 years: Initial: 300 mg loading dose, followed by 75 mg once
daily for up to 28 days (in combination with aspirin). Patients >75 years:
75 mg once daily for up to 28 days (with or without thrombolysis)
– Note:Coronary artery stents: Duration of clopidogrel (in combination with
aspirin): According to the ACC/AHA/SCAI guidelines, ideally 12 months
following drug-eluting stent (DES) placement in patients not at high risk
for bleeding

Opie et al, 2012. Drug for the Heart. 8th Ed

Lacy et al, 2009. Drug Information Handbook. 17th Ed
 Isosorbide Dinitrat

Effect of NO on myocardial relaxation and contractile protein

Opie LH and Jorowitz JD. Nitrates and newer antianginal. s. In: Opie LH and Gersh BJ (Eds.) Drugs for The Heart. 8th edition. 2013. Philadelphia:
Elsevier Saunders. P.93-105
Pharmacokinetics

Munzel and Gori, 2013

 First Line Therapies to Prevent
Nitrate Tolerance

Nitrate-Free Intervals
• Certain dosing of organic nitrates to provide a nitrate-free interval
(10-12 hours)

Disadvantage :
• potentially confusing dosing schedules and
• inconvenience to the patient,
• may be associated with worsening endothelial dysfunction and rebound
ischemia, with increased frequency and intensity of ischemic events.

Munzel, 2013
Alternatives Therapies to Prevent Nitrate Tolerance

ACE-Is and ARBs

• Tolerance to nitrates is thought to partially involve counterregulatory mechanisms
including volume expansion via sodium and water retention  mediated through the
renin/angiotensin system
(Katz, et al, 1991; Holden, 2013)

Antioxidants
• 2 randomized trials found oral vitamin C to be effective in ameliorating nitrate tolerance
(Münzel, 2013)

Statin
• Statin prevents both GTN-induced endothelial dysfunction and nitrate tolerance, likely
by counteracting the GTN-induced increase in oxidative stress (Liuni, et al. 2011)

Folic Acid
• Our data demonstrate that supplemental folic acid prevents both nitric oxide synthase
dysfunction induced by continuous GTN and nitrate tolerance in the arterial circulation
of healthy volunteers. (Gori, et al,2001)
ESO : RHABDOMYOLISIS DAN
HEPATOTOKSIK
BARU : EZETIMID
 Terapi Simvastatin

Patrick T. O’Gara et al. 2013. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, Journal of the American College of Cardiology Vol.
61, No. 4
HEPARIN DAN LMWH
 WARFARIN
ANTIKOAGULAN ORAL
ANTAGONIS VITAMIN K
WAKTU PARUH PANJANG
FARMAKOGENETIK CYP2C9
RENTANG TERAPI SEMPIT
INTERAKSI OBAT BANYAK
NOAC
PERBEDAAN FARMAKOKINETIK
WARFARIN VS NOAC
 PELAYANAN KEFARMASIAN

• EDUKASI KE PASIEN :
• KIE OBATNYA
• KIE PENYAKIT DAN KOMPLIKASINYA
• KIE POLA HIDUP SEHAT
• KIE KEPATUHAN MINUM OBAT DENGAN
BENAR DAN KONTROL TERATUR
 PELAYANAN KEFARMASIAN
• EDUKASI KE PASIEN :
• KIE OBATNYA
• KIE PENYAKIT DAN KOMPLIKASINYA
• KIE POLA HIDUP SEHAT
• KIE KEPATUHAN MINUM OBAT DENGAN
BENAR DAN KONTROL TERATUR
Terima kasih