ANGINA PECTORISTHROMBOLITYCANTI ARRYTHMIAPROF MOCH ARIS WIDODO PhDDEPARTMENT PHARMACOLOGY AND THERAPYMEDICAL FACULTY BRAWIJAYA UNIVERSITY
RISK FACTORSSMOKINGOBESITYHYPERTENSIVMETBOLIC SYNDROME
ACUTECORONARYSYNDROME
ANGINAMIOCARD INFARCTARRYTMIA
ANGINA PECTORIS NYERI DADA YANG BERASAL DARI JANTUNG DAN SERING KALI MENJALAR SAMPAI UJUNG JARI DANKE BAHU
NYERI OLEH KARENA OLEH KARENA TIDAK SESUAINYA KEBUTUHAN JARINGAN OTOT JANTUNG DENGAN SUPLAI OKSIGEN OLEH CABANG CABANG ARTERIKORONARIA
PENYEBAB :
SUPLAI OKSIGEN DAN BAHAN MAKANAN BERKURANG OLEH ARENA PENYEMPITAN PEMBULUHDARAH KORONER OLEH PENYUMBATAN ATAU TERJADI VASOKONSTRIKSI KPORONER
KEBUTUHAN YANG MENINGKAT MISALNYA PADALATIHAN TAKHIKARDI PENINGKATAN PRELOADATAU AFTER LOAD.
ALIRAN DARAH KE ARTERI KORONARIA
TERJADI PADA FASE DASTOLE OLEH KARENA:
OTOT JANTUNG RELAKSASIKATUP AORTA MENUTUPTEKANAN DIASTOLE YANG CUKUP
SISTOLE
DIASTOLE
AORTA
ARTERI KORONARIA
VENTRIKEL KIRI
TYPE TYPE ANGINA PECTORIS:
ATEROSCLEROTIC ANGINA : ANGINA DE EFFROT, ATAU ANGINA KLASIK. TERKAIT DENGAN ATHEROMA, 90%PENYEBAB ANGINA, PENYEMPITAN MENYEBABKAN ISKEMIA DAN METABOLIT ACID RASA NYERI SPESIFIKNYERI HILANG SAAT IATIRAHAT.
VASOSPASTIK ANGINA = REST ANGINA = PRINZMEAL ANGINA = VARIANT ANGINA VASOSPASNE REVERSIBLE DAPAT TERJADI SAAT ISTIRAHAT – DAPAT MENJADI UNSTABLE ANGINA
UNSTABLE ANGINA CRESCENDO ANGINA = SINDEROMA KORONER AKUT, TERJADI [ENINKATAN FREKUENSI DAN DERAJAT SERANGAN OK BERKURANGNYA FLOW KORONERDISEBABKAN OLEH PLAK ATEROSKLEROSIS. TROMBUS RUPTURE PLAK DAN VASOSPASME PREKUSOR UNTUKMIOKARD INFARK.
THERAPY ANGINA PECTORIS
PENCEGHAN ANGINA PECTORISPENGENDALIAN FAKTOR RESIKOMODIFIKASI LIFE STYLE
PEMASANGAN STENT
PENGOBATAN DENGAN OBATANTI LIPIDANTI TROMBOSISANTI ANGINA
OBAT UNTUK ANGINA PECTORIS MENGHILANGKAN NYERI
VASODILATOR ARTERI KORONARIA
VASODILATOR PERIPERMENGURANGI PRELOAD DAN
AFTER LOAD
MENGURANGI BEBAN JANTUNG
SYSTEMIC CIRCUATION REDUCED AFTER LOAD
BETA BLOCKER BETA BLOKER SA NODE CA ANTAGONIST NITRATES NEGATIF INOTROPICS
VERAPRAMIL ARTERIAL RESISTANCE
VESSELS DILTIAZEM
NITRATES Ca ANTAGONIST
REDUCED PRELOAD VENOUS CAPACANCE
VESSELS
REDUCED VENOUS RETURN
OBAT OBAT UNTUK ANGINA
VASODILATOR CARDIAC DEPRESANT
NITRATES CALSIUM ANTAGONIS BETA BLCKER
SHORT DURATION
INTERMEDIATE
LONG DURATION
GOLONGAN CONTOH OBAT DURATION
VERY SHORT IMHALED AMYL 3-5 MENIT NITRIT
SHORT NITROGLICERIN 10-30 MENIT ISOSORBID DINITRAT
SUBLINGUAL
INTERMDIATE NITROGLYCERINE 4-8 JAM ISOSORBIDE DINIRAT
ORAL
LONG NITROGLICERIN 8-10 JAM TRANS DERMAL PATCH
KELOMPOK NITRAT
MEKANISME KERJA KELOMPOK NITRAT
GLYCERYL TRINITRAT DIHEPAR
GLYCERYL DINITRAT EFEK VASODILATASI
MONONITRAT METABOLIT TAK ADA EFEK
DENITRASI GTN DIDALAM OTOT POLOSMENYBABKAN MELEPASKAN NO STIMULATEGUANILATE SIKLASE MENINGKATKAN C GMPDEPOSPORILATION OF MYOSIN LIGHT CHAINKINASE RELAKSASI OTOT POLOS PEMBULUH DARAH VASODILATASI
NITRAT :KARDIOVASKULER: RELAKSASI OTOT POLOS
PEMBULUH RAH MENYABABKAN PENURUNAN PROLOADDAN MENGUANGI BEBAN JANTUNGM BESAR JANTUNGDAN MENURUNKAN OUT PT JANTUNG PENURUNA AFTERLOAD TERJADI OLEH KARENA DILATASI ARTRIOLE MENURUNKAM TAHANAN PERIPER, MENURUNKAN TEKAMAM DARAH.
NITRAT MENYEBABKAN REFLEK TAKIKARDI
EFEK RELAKSASI OTOT POLOS LAIN KECIL
EFEK SAMPING :
TAKIKARDI REFLEK KOMPENSASI HYPOTENSIORTHOSTATIK HYPOTENSI NYERI KEPALA BERDENYUT
INTERAKSI DENGAN SIDEFANIL
SIDEFANIL (VIAGRA) MENGHAMBAT POSPODIESTRASE ISOFORM. MENURUNKAN PEMECAHAN C GMP
+NITRAT MENINGKATKAN SINTESA C GMP
SINERGISTIK RALAKSASI PEMBULUH ARAH HYPOTENSION, HYPOREPERFUSION PADA ORGAN PENTING
CALCIUM ANTAGONIS
DERIVAT DYHYDROPYRIDINE NIFEDIPINE DILTIAZEMVERAPRAMIL
MEKANISME MENGHAMBAT KANAL KALSIUM TYPE L DIOTOT POLOS PEMBULUH DARAH DAN JANTUNG SEHINGGAINFLUK KALSIUM SAAT TERJADINYA AKSI POTENSIALMENURUN --- DILATAS PEMBULUH DARAH
EFEK FARMAKOLOGI RELAKSASO PEMBULUH ARAH HIPOENSI DAN PENURUNAN KONTRAKSI DAN FREKUENSIJANTUNG
KEGUNAAN : ANGINA, HYPERTENSI, TAKHIKARDI SUPRAVENTRIKEL, MIGRAIN DAN RAYNODE DISEASE
BETA BLOKER
MENGHAMBAT KONTRAKSI JANTUNG DENGANMENGHALNGI IKATAN LIGAND DALAM HALINI NOR ADRENERGIC ATAU NEROTRANSMITERBERIKATAN DENGAN RESEPTOR BETA 1
EFEK SAMPING BBETA BLOKER JUGA MENCEGAH IKATAN NEROTRANSMITER DENGAN RESEPTOR BETA 2 DENGAN AKIBAT BRONCHO KONSTRIKSI
BETA BLOKER
MENGHAMBAT KONTRAKSI JANTUNG DENGANMENGHALNGI IKATAN LIGAND DALAM HALINI NOR ADRENERGIC ATAU NEROTRANSMITERBERIKATAN DENGAN RESEPTOR BETA 1
EFEK SAMPING BBETA BLOKER JUGA MENCEGAH IKATAN NEROTRANSMITER DENGAN RESEPTOR BETA 2 DENGAN AKIBAT BRONCHO KONSTRIKSI
MIOCARD INFARCTACUTE CORONARY SYNDROMES
AND THROMBOLITYC
ANGINA UNSTABLE
CRESCENDO ANGINA
MIOCARD INFACRT
Stable plaque
rupture
thrombosss
Embolitroponin
restabilized
Gp Iib/IIIa
Intact endothelim
Anti aggregratoryVia prostacyclin
VasodilatoryVia nitric oxide
FibrinolyticVia tPA
Anti thrombotic Via thrombomedulin
Damaged vascular endothelium
Platelet adhesionPlatelet activation
Platelet aggregration
Clotting mechanism Formation of fibrin
Back bone of thrombus
Clinical sydrome ofAcute myocard infarct
Peripheral arterial thrmbosis
Platelet inhibitorPrevent AMITIA (aspirin)
Anticoagulant given Acutely to prevent Further formation ofFibrin (heparin)To prevent thrmboEmbolism (warfarin)
Fibrinolytic agentsFor clinical syndromesAMI and phripheralArterial thrombosis
EARLY PHASE AMIRUSH TO ICURAPID LYSIS PCIPAIN RELEIFASPRINBETA BLOCKERACE INHIBITORFUTUE STEM CELL
REPERFUSION
CHRONIC PHASESTATINASPIRIN /CLOPIDOGRELACE INHIBITORPCI / BYPASS
REMODELLINGPREVENT CHVACE INHIITORBETA BLOKERHYPERTENSI
PREVENT SUDDEDDEATHBETA LOCKER
ANTI PLATELET AGENTSTICLOPIDINE : thienoyridine derivat irreversibly inhibit the
binding of ADP to is receptor on the platelets side effects : neutropenia, thrombocytopenia
CLOPIDOGREL: same as above, lower myelotoxiciy, GI effects same as aspirin
DIPYRIDAMOLE: the effects same as aspirin, no longer use inhibit COX, dangerous interaction with adenosine
SULFINPYRAZOLE: same as dypyridamol
GYCOPROTEIN IIb/IIIa RECEPTOR ANTAGONIST: ABCIXICIMA: monoclonal antibody against IIb/IIIa receptorTIROFIBAN : Nonpeptida peptidomeric Iia/IIIb inibitorEFTIFIBATIDE : A synthetic cyclic heptapeptida
PLATELET INHIBITION
ASPIRIN
INHIBITION OF COX 1 inhibit synthesis of thombin side effect GI bleeding weak inhibition of COX2 weak anti inflamatory
ASPIRIN RESISTANCE
CLINICAL USE after MI, angina, after stroke after by pass surgery, diabetes, well treated hypertension
Primary prevention of aspirin only those at high risk group
drug interaction NSAIDS, warfarin, ACE inhibitor
ACUTE ANTI koagulant
HEPARIN oral : diberikan secara intra vena
WARFARIN: diberikan secara
FIBRINOLYTIC (THOMBOLYTIC) HERAPYGoal of therapy : reperfusion , early patency, salvage cardiac miocyte from cell death , improve remodeling, enhance electrical stability reduced long term mortalityGolden period: 1 hours - 7-12 hours reduced mortality rate and reduce infarct sizePrehospital fibrinolytic therapy is more better
ALTEPLASETpa, Tissue plasminogen activator a naturally occuring enzyme
that bind to fibrin convert plasminogen to plasmin very short half life intra venous side effect: hemorrhage contra indication CVA, postoperation
TENECTEPLASE: genetically enginered mutant of tPA decrease plasma clearance longer half life iv sigle bolus
RETEPLASE: deletion mutant of ateplase longer plasma clearance 10U+10U for 10 minute each 30 minute apart
STREPTOKINASE : no direct effect on plasminogen it work by binding to plasminogen to form a complex to convert plasminogen to plasmin dose 1.5 million unit in 100ml saline over 30 to60 minute
Contra indication of fibrinolyticsuspected aortic dissectionprevious history of hemorrhage stroke central nervous system damage within1 yearhead trauma / brain surgeryinternal bleeding within 6 weeksactive bleeding / bleeding disordermayor surgery within 6 weekstraumatic cardio respiratory resusitationpersistent serious hypertensionoral anticoagulant therapypeptic ulcer diseaseintracranial neoplasmacute pancraetitisPregnancy / within 1 week postpartumdementiatransient ischemic attack (TIA)infective endocarditisactive cavitating TBCadvanced liver diseaseintra cardiac thrombi
ANTI ARRYTHMIA DRUGS
OBAT ARITMIA JANTUNGCardiac cells undergo depolarization and repolarization to
form cardiac action potentials about sixty times per minute. The shape and duration of each action potential are
determined by the activity of ion channel protein complexes in the membranes of individual cells, and the genes encoding most of these proteins now have been identified.
Thus each heartbeat results from the highly integrated electrophysiological behavior of multiple proteins on multiple cardiac cells.
Ion channel function can be perturbed by acute ischemia, sympathetic stimulation, or myocardial scarring to create abnormalities of cardiac rhythm, or arrhythmias.
Available antiarrhythmic drugs suppress arrhythmias by blocking flow through specific ion channels or by altering autonomic function.
Mekanisme aritmia jantungWhen the normal sequence of impulse
initiation and propagation is perturbed, an arrhythmia occurs.
Failure of impulse initiation may result in slow heart rates (bradyarrhythmias)
Failure of impulses to propagate normally from atrium to ventricle results in dropped beats or "heart block"
These abnormalities may be caused by drugs or by structural heart disease
Three major underlying mechanisms have been identified: enhanced automaticity, triggered automaticity, and re-entry.
Enhanced Automaticity
Enhanced automaticity may occur in cells that normally display spontaneous diastolic depolarizationthe sinus and AV nodes and the His-Purkinje system. b Adrenergic stimulation, hypokalemia, and mechanical stretch of cardiac muscle cells increase phase 4 slope and so accelerate pacemaker rate,
acetylcholine reduces pacemaker rate both by decreasing phase 4 slope and by hyperpolarization (making the maximum diastolic potential more negative).
In addition, automatic behavior may occur in sites that ordinarily lack spontaneous pacemaker activity; e.g., depolarization of ventricular cells (e.g., by ischemia) may produce such "abnormal" automaticity.
Afterdepolarizations and Triggered Automaticity
Under some pathophysiological conditions, a normal cardiac action potential may be interrupted or followed by an abnormal depolarization If this abnormal depolarization reaches threshold, it may, in turn, give rise to secondary upstrokes that can propagate and create abnormal rhythms. These abnormal secondary upstrokes occur only after an initial normal, or "triggering," upstroke and so are termed triggered rhythms.
Na Ca K K NaNa-K ATP ase
0
+30
- 90
KONDUKSIADANYA BLOK AUTOMATISITYFREKUENSI
AKSI POTENSIAL DAN TERJADINYA ARRITMIA
INTRA SEL
Triggered Automaticity
Two major forms of triggered rhythms are recognized. In the first case, under conditions of intracellular Ca2+ overload (e.g., myocardial ischemia, adrenergic stress, digitalis intoxication, or heart failure), a normal action potential may be followed by a delayed afterdepolarization (DAD). If this afterdepolarization reaches threshold, a secondary triggered beat or beats may occur. In the second type of triggered activity, the key abnormality is marked prolongation of the cardiac action potential. When this occurs, phase 3 repolarization may be interrupted by an early afterdepolarization (EAD). When cardiac repolarization is markedly prolonged, polymorphic ventricular tachycardia with a long QT interval, known as the torsades de pointes syndrome, may occur. Congenital long QT syndrome, a disease in which torsades de pointes is common, can be caused by mutations in the genes encoding the Na+ channels or the channels underlying the repolarizing currents
Re-entry
Anatomically Defined Re-entry. Re-entry can occur when impulses propagate by more than one pathway between two points in the heart, and those pathways have heterogeneous electrophysiological properties. Patients with Wolff-Parkinson-White (WPW) syndrome have accessory connections between the atrium and ventricle With each sinus node depolarization, impulses can excite the ventricle via the normal structures (AV node) or the accessory pathway. However, the electrophysiological properties of the AV node and accessory pathways are different.
PENGOBATAN ARITMIA :
JENIS ARITMIAS DIIDENTIFIKASI
PENYEBAB YANG REVERSIBLE DIHILANGKAN
DINILAI KEPENTINGAN RISK DAN BENEFIT DARI TERAPI
ATRIAL ARITMIA DAN AV NODAL REENTRAN TAKIKARDIVERNTIKULAR ARITMIA ----- ANCAMAN SUDEN DEATH
PEMILHAN OBAT HARUS DIPAHAMI
FARMAKODINAMI OBAT OBAT ARITMIA
FARMAKOKINETIK OBAT ARITMIA
PENYAKIT YANG MENYERTAI ARITMIA
ARRITMIA JANTUNG
SUPRAVENTRIKULER VENTRIKULER
FOKUS ECTOPIK DI ATAS A-V NODE DI VENTRIKEL
HEMODINAMIK RINGAN BERAT COLLAPS
SUDDEN DEATH TIDAK ANCAMAN
CONTOH ATRIAL TAKIKARDI VES ATRIAL FLUTER VENT. TAKIKARDI
VEBNT FIBRILASI
PENYEBAB ARITMIA YANG REVERSIBEL
OBAT OBATANDIGITALIS ANTI ARRITMIATHEOPHILIN CATHECOLAMINETRISIKLIK ANTI DEPRESAN PHENOTHIAZINEANOREKSIAN OBAT ANAESTHESI
FAKTOR JANTUNGISKEMIA JANTUNG CHF
PENYAKIT LAINTHYROTOKSIKOSIS LUNG DISEASE
GANGGUAN METABOLIKASIDOSIS ALKALOSISHYPOKSIA HYPERKALEMIAHYPOMAGNESEMIA HYPOKALEMIA
ARRITMIA JANTUNG HILANG APABILA FAKTOR TERSEBUTDIPERBAIKI
DIAGNOSEPEMERIKSAAN ECG
DILAKUKAN MONITOR 24 – 72 JAMDILAKUKAN TEST EXERCISE PEMERIKSAAN ELEKTRO FISIOLOGIS PEMERIKSAAN 12 LEAD ECG ATAU OESOPHAGUS ECG
DIHILANGKAN PENYEBAB
DILAKUKAN TERAPI OBAT
DILAKUKAN TERAPI DEFIBRILASI
PEMASANGAN PACU JANTUNG
OBAT ARRITMIA JANTUNG :
I. SODIUM CHANNEL BLOKER : KELAS I a KELAS I bKELAS I c
II. BETA ADRENERGIK AGONIS
III PROLONGATION OF THE ACTION POTENTIAL
IV. A-V NODAL CALCIUM CHANNEL BLOCKER
LAIN –LAIN
DATA FARMAKOKINETIK OBAT ARITMIA YANG DIBERIKANSECARA INTRA VENA
OBAT LOADING MAINTENANCE THER. PLASMA CONC
LIDOCAIN 3-4 MG/KG 1-4 MG/MIN 1.5-5 UG/ML
BRETYLIUM 5-30 MG/KG 1-4MG/MIN -
PROCAINAMIDE 10-20 MG/KG 1-4 MG/MIN 4-10 UG/ML 20 MG/MIN
VERAPRAMIL 1-20 MG/KG
ADENOSIN 2-20 MG/KG
ESMOLOL 500 UG/KG(50UG/KG/MIN) 100-200 UG/KG
PROPANOLOL 1-5 MG
PENYAKIT DAN OAT OBAT YANG MENYEBABKAN PERUBAHAN FARMAKOKINETIK
CONGESTIVE HEART FAILURE ---- DISTRIBUSI OBAT
KELAINAN HEPAR ------- METABOLISME OBATBINDING PROTEIN
GAGAL GINJAL ------------------- EKSKRESI OBAT MENURUN
PENGOBATAN LAIN MISALNYA PHENO BARBITAL MENINGKATKAN METABOLISME OBAT
OBAT PILIHAN PENAALAKSANAN ARITMIA
ARITMIA ACUT KRONIS
ATRIAL FIBRILASI/ FLUTER DIGITALIS , VERAPRAMIL SAMA BETA BLOKER
AV NODAL ENTRY ADENOSINE , VERAPRAMIL QUINIDINE, PROCAINAMIDE AMIODARONE, FLECAINIDE
WOLF PARKINSON WHITE ADENOSINE, VERAPRAMIL KELAS Ic DAN Kelas 1aSYNDEROME BETA BLOKER
ATRIAL FIBRILASI DENGAN PROCAIN AMIDE PROCAINAMIDE , QUINIDINEPREEXCITEN VENRICULAER KELAS IcCOMPLEXES
AUTOMATIC ATRIAL A-V NODAL BLOKER VERAPRAMIL, KELAS IaTAKHIKARDI KELAS Ic
AKUT KRONISPREMATURE VENTRICULAR BEAT AND NO SUSTAINED VENTRIKULAR ARRITMIA ASYMPTOMATIC - - SYMPTOMATIC - BETA BLOKER
KELAS Ia/ Ic SUSTAINED VENTRK. TAKIKARDI LIDOCAIN KELAS Ia
PROCAINAMIDE KELAS Ic BRETYLIUM BETA BLOKER
VNTRIKULAR FIBRILASI LIDOCAIN - PROCAINAMIDE BRETYLIUM
WIDE COMPLEX TAKHIKARDI PROCAINAMIDE LIDOCAINE
ADENOSINE HINDARI VERAPRAMIL
NAROW COMPLEX TAKHIKARDI ADENOSINE VERAPRAMIL
KONTRA INDIKASI RELATIF OBAT ANTI ARRITMIA
NON CARDIACPENYAKIT GI QUINIDINEPROSTATISM, RETENSI URINEGLAUCOMA DYSOPYRAMIDEARTRITIS INFLAMASI MEXILETIN , TOCAINIDETREMOR LIDOCAINBRONCHO SPASM BETA BLOKER, PROPAFENONEPENY. PARU AMIODARONEPSIEN MUDA AMIODARONE, PRODCAINAMIDE
CARDIACCHF DYSOPYRAMIDE, FLECAINIDE,STENOSIS AORTA BETA ANTAGONIS, VERAPRAMIL,CARDIOMYOPATHI BRETYLIUM, KELAS 1 a dan IIIHYPERTENSI PU;LMONAL
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