ANGINA PECTORIS

THROMBOLITYC
ANTI ARRYTHMIA
PROF MOCH ARIS WIDODO PhD
DEPARTMENT PHARMACOLOGY AND THERAPY
MEDICAL FACULTY BRAWIJAYA UNIVERSITY
RISK FACTORS
SMOKING
OBESITY
HYPERTENSIV
METBOLIC SYNDROME

ACUTE
CORONARY
SYNDROME

ANGINA
MIOCARD INFARCT
ARRYTMIA
ANGINA PECTORIS
NYERI DADA YANG BERASAL DARI JANTUNG DAN
SERING KALI MENJALAR SAMPAI UJUNG JARI DAN
KE BAHU

NYERI OLEH KARENA OLEH KARENA TIDAK SESUAINYA

KEBUTUHAN JARINGAN OTOT JANTUNG DENGAN
SUPLAI OKSIGEN OLEH CABANG CABANG ARTERI
KORONARIA

PENYEBAB :
SUPLAI OKSIGEN DAN BAHAN MAKANAN BERKU
RANG OLEH ARENA PENYEMPITAN PEMBULUH
DARAH KORONER OLEH PENYUMBATAN ATAU
TERJADI VASOKONSTRIKSI KPORONER

KEBUTUHAN YANG MENINGKAT MISALNYA PADA

LATIHAN TAKHIKARDI PENINGKATAN PRELOAD
ATAU AFTER LOAD.
 ALIRAN DARAH KE ARTERI KORONARIA

TERJADI PADA FASE DASTOLE OLEH KARENA:

OTOT JANTUNG RELAKSASI

KATUP AORTA MENUTUP
TEKANAN DIASTOLE YANG CUKUP

DIASTOLE

AORTA

ARTERI KORONARIA

VENTRIKEL KIRI
SISTOLE
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 SPESIFIK
NYERI HILANG SAAT IATIRAHAT.

VASOSPASTIK ANGINA = REST ANGINA = PRINZMEAL ANGINA

= VARIANT ANGINA VASOSPASNE REVERSIBLE DAPAT TER
JADI SAAT ISTIRAHAT – DAPAT MENJADI UNSTABLE ANGINA

UNSTABLE ANGINA CRESCENDO ANGINA = SINDEROMA

KORONER AKUT, TERJADI [ENINKATAN FREKUENSI DAN
DERAJAT SERANGAN OK BERKURANGNYA FLOW KORONER
DISEBABKAN OLEH PLAK ATEROSKLEROSIS. TROMBUS
RUPTURE PLAK DAN VASOSPASME  PREKUSOR UNTUK
MIOKARD INFARK.
THERAPY ANGINA PECTORIS

PENCEGHAN ANGINA PECTORIS

PENGENDALIAN FAKTOR RESIKO
MODIFIKASI LIFE STYLE

PEMASANGAN STENT

PENGOBATAN DENGAN OBAT

ANTI LIPID
ANTI TROMBOSIS
ANTI ANGINA
OBAT UNTUK ANGINA PECTORIS MENGHILANGKAN NYERI

VASODILATOR ARTERI KORONARIA

VASODILATOR PERIPER
MENGURANGI 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
 KELOMPOK NITRAT

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
MEKANISME KERJA KELOMPOK NITRAT

GLYCERYL TRINITRAT  DIHEPAR

GLYCERYL DINITRAT  EFEK VASODILATASI

MONONITRAT  METABOLIT TAK ADA EFEK

DENITRASI GTN DIDALAM OTOT POLOS

MENYBABKAN MELEPASKAN NO  STIMULATE
GUANILATE SIKLASE  MENINGKATKAN C GMP
DEPOSPORILATION OF MYOSIN LIGHT CHAIN
KINASE  RELAKSASI OTOT POLOS PEMBULUH
DARAH  VASODILATASI
NITRAT :
KARDIOVASKULER: RELAKSASI OTOT POLOS
PEMBULUH RAH MENYABABKAN PENURUNAN PROLOAD
DAN MENGUANGI BEBAN JANTUNGM BESAR JANTUNG
DAN MENURUNKAN OUT PT JANTUNG
PENURUNA AFTERLOAD TERJADI OLEH KARENA DILATASI
ARTRIOLE  MENURUNKAM TAHANAN PERIPER,  MENU
RUNKAN TEKAMAM DARAH.

NITRAT MENYEBABKAN REFLEK TAKIKARDI

EFEK RELAKSASI OTOT POLOS LAIN KECIL

EFEK SAMPING :

TAKIKARDI REFLEK KOMPENSASI HYPOTENSI

ORTHOSTATIK 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
DILTIAZEM
VERAPRAMIL

MEKANISME MENGHAMBAT KANAL KALSIUM TYPE L DI

OTOT POLOS PEMBULUH DARAH DAN JANTUNG SEHINGGA
INFLUK KALSIUM SAAT TERJADINYA AKSI POTENSIAL
MENURUN --- DILATAS PEMBULUH DARAH

EFEK FARMAKOLOGI RELAKSASO PEMBULUH ARAH

HIPOENSI DAN PENURUNAN KONTRAKSI DAN FREKUENSI
JANTUNG

KEGUNAAN : ANGINA, HYPERTENSI, TAKHIKARDI SUPRA

VENTRIKEL, MIGRAIN DAN RAYNODE DISEASE
BETA BLOKER

MENGHAMBAT KONTRAKSI JANTUNG DENGAN

MENGHALNGI IKATAN LIGAND DALAM HAL
INI NOR ADRENERGIC ATAU NEROTRANSMITER
BERIKATAN 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 DENGAN

MENGHALNGI IKATAN LIGAND DALAM HAL
INI NOR ADRENERGIC ATAU NEROTRANSMITER
BERIKATAN DENGAN RESEPTOR BETA 1

EFEK SAMPING
BBETA BLOKER JUGA MENCEGAH IKATAN
NEROTRANSMITER DENGAN RESEPTOR BETA 2
DENGAN AKIBAT BRONCHO KONSTRIKSI
 MIOCARD INFARCT
ACUTE CORONARY SYNDROMES
AND THROMBOLITYC
ANGINA UNSTABLE

CRESCENDO ANGINA

MIOCARD INFACRT
 Stable plaque

restabilized
rupture

Emboli
troponin

thrombosss
Gp Iib/IIIa
 Anti aggregratory
Via prostacyclin

Vasodilatory
Via nitric oxide

Intact endothelim Fibrinolytic

Via tPA

Anti thrombotic
Via thrombomedulin
 Platelet inhibitor
Prevent AMI
TIA (aspirin)
Damaged vascular endothelium

Platelet adhesion
Anticoagulant given
Platelet activation
Acutely to prevent
Platelet aggregration
Further formation of
Fibrin (heparin)
Clotting mechanism
To prevent thrmbo
Formation of fibrin
Embolism (warfarin)
Back bone of thrombus

Clinical sydrome of
Acute myocard infarct
Fibrinolytic agents
Peripheral arterial thrmbosis
For clinical syndromes
AMI and phripheral
Arterial thrombosis
 EARLY PHASE AMI
RUSH TO ICU
RAPID LYSIS PCI
PAIN RELEIF
ASPRIN
BETA BLOCKER
ACE INHIBITOR
FUTUE STEM CELL

REPERFUSION

CHRONIC PHASE
STATIN REMODELLING
ASPIRIN /CLOPIDOGREL PREVENT CHV
ACE INHIBITOR ACE INHIITOR
PCI / BYPASS BETA BLOKER
HYPERTENSI

PREVENT SUDDED
DEATH
BETA LOCKER
ANTI PLATELET AGENTS
TICLOPIDINE : 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 receptor
TIROFIBAN : Nonpeptida peptidomeric Iia/IIIb inibitor
EFTIFIBATIDE : 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) HERAPY
Goal of therapy : reperfusion , early patency, salvage cardiac miocyte from
cell death , improve remodeling, enhance electrical stability
reduced long term mortality
Golden period: 1 hours - 7-12 hours reduced mortality rate and
reduce infarct size
Prehospital fibrinolytic therapy is more better
ALTEPLASE
Tpa, 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 fibrinolytic
suspected aortic dissection
previous history of hemorrhage stroke
central nervous system damage within1 year
head trauma / brain surgery
internal bleeding within 6 weeks
active bleeding / bleeding disorder
mayor surgery within 6 weeks
traumatic cardio respiratory resusitation
persistent serious hypertension
oral anticoagulant therapy
peptic ulcer disease
intracranial neoplasm
acute pancraetitis
Pregnancy / within 1 week postpartum
dementia
transient ischemic attack (TIA)
infective endocarditis
active cavitating TBC
advanced liver disease
intra cardiac thrombi
ANTI ARRYTHMIA DRUGS
OBAT ARITMIA JANTUNG
 Cardiac 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 jantung
When 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 depolarization
the 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.
 AKSI POTENSIAL DAN TERJADINYA ARRITMIA

+30 KONDUKSI
ADANYA BLOK
0 AUTOMATISITY
FREKUENSI

- 90

Na-K ATP ase

Na Ca K K Na 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 TAKIKARDI

VERNTIKULAR 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 OBATAN
DIGITALIS ANTI ARRITMIA
THEOPHILIN CATHECOLAMINE
TRISIKLIK ANTI DEPRESAN PHENOTHIAZINE
ANOREKSIAN OBAT ANAESTHESI

FAKTOR JANTUNG
ISKEMIA JANTUNG CHF

PENYAKIT LAIN
THYROTOKSIKOSIS LUNG DISEASE

GANGGUAN METABOLIK
ASIDOSIS ALKALOSIS
HYPOKSIA HYPERKALEMIA
HYPOMAGNESEMIA HYPOKALEMIA

ARRITMIA JANTUNG HILANG APABILA FAKTOR TERSEBUT

DIPERBAIKI
DIAGNOSE
PEMERIKSAAN ECG

DILAKUKAN MONITOR 24 – 72 JAM

DILAKUKAN 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 b
KELAS 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 DIBERIKAN
SECARA 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 OBAT

BINDING 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 1a

SYNDEROME BETA BLOKER

ATRIAL FIBRILASI DENGAN PROCAIN AMIDE PROCAINAMIDE , QUINIDINE

PREEXCITEN VENRICULAER KELAS Ic
COMPLEXES

AUTOMATIC ATRIAL A-V NODAL BLOKER VERAPRAMIL, KELAS Ia

TAKHIKARDI KELAS Ic
 AKUT KRONIS
PREMATURE 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 CARDIAC
PENYAKIT GI QUINIDINE
PROSTATISM, RETENSI URINE
GLAUCOMA DYSOPYRAMIDE
ARTRITIS INFLAMASI MEXILETIN , TOCAINIDE
TREMOR LIDOCAIN
BRONCHO SPASM BETA BLOKER, PROPAFENONE
PENY. PARU AMIODARONE
PSIEN MUDA AMIODARONE, PRODCAINAMIDE

CARDIAC
CHF DYSOPYRAMIDE, FLECAINIDE,
STENOSIS AORTA BETA ANTAGONIS, VERAPRAMIL,
CARDIOMYOPATHI BRETYLIUM, KELAS 1 a dan III
HYPERTENSI PU;LMONAL