PELAYANAN KEFARMASIAN PADA PENYAKIT JANTUNG KORONER SUHARJONO DEP FARMASI KLINIK UNIVERSITAS AIRLANGGA Hotel Harries, Surabaya, 21 Agustus 2016 EduPharma II DEFINISI • ATHEROSCLEROSIS adalah penumpukan lemak di bagian intima arteri, yang awalnya lunak dan mengeras bila lama • ARTERY DISEASE (CAD) 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) Fakta tentang Jantung • Bila jantung berdenyut 70 kali / menit • Sekali denyut 70cc darah 5 liter /menit Curah Jantung • 70cc darah mengitari ± 100.000 km pembuluh • berdenyut ± 100.000 x/hari • 2,5 milyar x/ sepanjang hidup • memompakan darah lebih dari 227 juta liter 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 busa Ruptur / bocor Trombus/ters umbat Komposisi plak dan sumbatan: LDL-C, sel2 radang dan bekuan darah ( trombus ) PROSES PERKEMBANGAN ATEROSKLEROSIS (Schaefer, 2010) 15 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. 2. Electrocardiogram (ECG) 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) 21 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 PELAYANAN KEFARMASIAN • • • • • EDUKASI KE PASIEN : KIE OBATNYA KIE PENYAKIT DAN KOMPLIKASINYA KIE POLA HIDUP SEHAT KIE KEPATUHAN MINUM OBAT DENGAN BENAR DAN KONTROL TERATUR Salahuddin, et al, 2014. Pathophysiological Mechanisms of Tobacco-related CVD. Global Heart Vol 7 no 2 2012 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