TERAPI OBAT PADA

SINDROMA KORONER AKUT &

GAGAL JANTUNG
Dra. Endang Martiniani M.Pharm
KLAS I Bukti dan/atau kesepakatan bersama bahwa pengobatan
tersebut efektif
KLAS II Bukti dan/atau pendapat yang berbeda tentangmanfaat
pengobatan tersebut
KLAS IIa Bukti dan pendapat lebih mengarah pada manfaat atau
kegunaan sehingga beralasan untuk dilakukan
KLAS IIb Manfaat atau efektivitas kurang didukung oleh bukti atau
pendapat, namun dapat dipertimbangkan untuk dilakukan.
KLAS III Bukti atau kesepakatan bersama bahwa pengobatan tersebut
tidak berguna atau tidak efektif, bahkan pada beberapa kasus
kemungkinan membahayakan.
TINGKAT BUKTI A Data berasal dari beberapa penelitian klinik acak berganda
atau meta analisis
TINGKAT BUKTI B Data berasal dari satu penelitian acak berganda atau
beberapa penelitian tidak acak
TINGKAT BUKTI C Data berasal dari konsensus opini para ahli dan/atau
penelitian kecil, studi retrospektif, atau registri
 DEFINISI
SKA : suatu kondisi dimana terjadi penurunan aliran
darah ke jantung secara mendadak dg gejala spt
ada tekanan di dada, sesak sampai tidak dpt
melakukan aktifitas fisik, muntah, mual, nyeri
bagian tubuh lain

NSTEMI : infark akut yang terjadi tanpa elevasi ST

yang sangat mirip dengan angina yang tidak stabil,
namun disertai peningkatan enzyme cardiac marker.
Hal ini terjadi karena adanya oklusi parsial di arteri
koroner
 DEFINISI
STEMI : infark akut yg terjadi dengan elevasi ST
akibat rusaknya bagian otot jantung secara
permanen akibat insufisiensi aliran darah
koroner yang ditandai dengan gejala SKA. Hal ini
terjadi karena adanya oklusi total arteri koroner
yang menyebabkan nekrosis pd seluruh atau
hampir seluruh lapisan dinding jantung.
STEMI

Hamm et al., 2006 9

 NON-PHARMACOLOGIC
TREATMENT
• Percutaneous transluminal coronary
angioplasty (PTCA)

• Intra-aortic balloon pump (unt STEMI)

• Coronary artery bypass graft (CABG)

 TREATMENT NSTEMI
• Dual platelet inhibition (aspirin & clopidrogel
atau gol thienopyridine)
• Nitrate
• Beta blocker
• ACEI (unt LV dysfunction)
• Aldosteron antagonist
• Statin
• Fractionated / Unfractionated heparin
 TREATMENT
TREATMENT STEMI
STEMI
• Fibrinolytics
• Unfractionated heparin
• Dual platelet inhibition
• Beta blocker
• ACEI (unt LV Dysfunction)
• Aldosteron antagonist
• statin
 ANTI-HTN pd ACS
• Anti-ischemia : beta-blocker, CCB
• ACEI : LV dysfunction
• Mineralcorticoid antagonis (spironolactone)
terutama bila LVEF < 40%
Dipiro et al., 14
2008
ANTI-COAGULANT
1. Direct Thrombin inhibitor Recombinant Hirudin Bivalirudin
Synthetic Argatroban
Ximelagatran
2. Indirect Thrombin Inhibitor Anti-thrombin III Heparin
activator Unfractionated Heparin
Low Molecular Weight
Heparin (Enoxaparinux)
Sselective factor Xa Fondaparinux
inhibitor
3. Indirect acting (Vit K Coumarin Warfarin
antagonist)
ANTI-PLATELET
1. Thromboxane A2 synthesis Aspirin
inhibitor
2. Meningkatkan c.AMP & c. GMP Dipyridamol
pentoxyfilline
3. Bekerja pd reseptor platelet Blok ADP receptor Clopidrogel
4. Blok GP Iib/IIIA receptor Abciximab
 INDIKASI
GOLONGAN
ANTI-COAGULANT Myocardial infarction
Pulmonary embolism
Venous & Cerebral embolism
ANTI-PLATELET
17
 Sites of action of antithrombotics

Enoxaparin

Opie & Gersh, 18

2013
MECHANISM OF ACTION STREPTOKINASE-ENOXAPARIN

19
 MEKANISME ASA DAN CLOPIDOGREL
ASPIRIN
Irreversibly inhibits cyclooxygenase-1 and 2
(COX-1 and 2) enzymes, via acetylation, which
results in decreased formation of prostaglandin
precursors; irreversibly inhibits formation of
prostaglandin derivative, thromboxane A2, via
acetylation of platelet cyclooxygenase, thus
inhibiting platelet aggregation; has antipyretic,
analgesic, and anti-inflammatory properties

CLOPIDOGREL
Requires in vivo biotransformation to an active
thiol metabolite. The active metabolite irreversibly
blocks the P2Y12 component of ADP receptors
on the platelet surface, which prevents activation
of the GPIIb/IIIa receptor complex, thereby
reducing platelet aggregation. Platelets blocked by
clopidogrel are affected for the remainder of their
lifespan (~7-10 days).
20
Opie & Gersh. 2013. Drugs for Heart. 2013
 PK/PD ASA-CLOPIDOGREL
PARAMETER ASPIRIN CLOPIDOGREL

Absorption Rapid. Well absorbed.

Distribution Vd : 10 L, readily into most body fluids and tissues.

Protein binding Parent drug : 98%; Inactive metabolite : 94%.

Hydrolyzed to salicylate (active) by esterases in GI
mucosa, red blood cells, synovial fluid, and blood;
Metabolism
metabolism of salicylate occurs primarily by hepatic
conjugation; metabolic pathways are saturable.
Excretion Urine (75% as salicyluric acid, 10% as salicylic acid)
Onset of action
Duration 4-6 hours
Extensively hepatic via esterase-mediated hydrolysis to a
carboxylic acid derivative (inactive) and via CYP450-
mediated (CYP2C19 primarily) oxidation to a thiol
metabolite (active).
Following administration of a single C-labeled clopidogrel
oral dose; radioactivity measured over 5 days: Urine
(50%); feces (46%).
300-600 mg loading dose: Detected within 2 hours 50-100
mg/day: Detected by the second day of treatment

Bioavailability 50-75% reaches systemic circulation

Parent drug: 15 to 20 minutes; Salicylates (dose
t½ dependent): 3 hours at lower doses (300-600 mg), 5-6 Parent drug : ~6 hours; Active metabolite : ~30 minutes.
hours (after 1 g), 10 hours with higher doses
Time to peak
1-2 hours. 0.75 hours.
serum 21
Lexicomp. 2015.
22
23
24
 PLEOTROPIC EFFECT OF STATIN
Pleotropic effect of statin (Mishra, 2008)
Lipid Dependent : Lipid Independent :
Decrease vascular Decrease LV mass
atherosclerosis -Inhibit angiotensin I-mediated cardiomyocyte hypertrophy
Decrease -Decrease extracellular signal-related kinase (ERK ½)
myocardial infarction activity, ERK phosphorylation, RAS membrane targeting and
Decrease cerebral activation
vascular accident -Antihypertensive
Decrease peripheral Decrease LV fibrosis
vascular diease -Decrease inflammation (decreased C-reactive protein,
interleukin-6), immune activation, oxidative stress, oxygen
free radicals
-Alter matrix metalloproteinase activity
Increase arterial compliance
-Decrease vascular atherosclerosis, endothelin synthesis
-Improve endothelial function
-Increase nitric oxide

25 Mishra, 2008. Role of Statin in Heart Failure

 TERAPI AWAL
(di IGD sebelum ada ECG/cardiac enzyme)

1 Tirah baring Klas IC

2 O2 bila SaO2 <95% atau ada distres respirasi Klas IC
Atau pd semua px SKA dlm 6 jam pertama Klas IIa
3 Aspirin 160-320 mg tidak bersalut Klas Ia
Aspirin bersalut Klas Ic
4 Adenosine diphosphate inhibitor : Klas IC
Clopidrogel 300 mg dilanjutkan dg 75 mg/hari
5 NTG sub lingual bila nyeri dada msh dirasakan Klas IC
saat di IGD. Diberikan tiap 5 menit maks 3x I
Bila tidak responsif, berikan NTG iv atau ISDN
6 Morfin iv 1-5 mg diulang tida 10-30’ bila tidak Klas IIA
responsif dg NTG
MORTALITAS 30 hari
CONGESTIVE HEART FAILURE /
DECOMPENSATION CORDIS
FUNCTIONAL CLASS (DCFC)
GEJALA
NYHA Classification of heart failure
• Class I: No limitation of physical activity
• Class II: Slight limitation of physical activity
• Class III: Marked limitation of physical
activity
• Class IV: Unable to carry out physical
activity without discomfort
 Goals of treatment
• To improve symptoms and quality of life
• To decrease likelihood of disease
progression
• To reduce the risk of death and need for
hospitalisation
 Main causes
• Coronary artery disease
• Hypertension
• Valvular heart disease
• Cardiomyopathy
• Cor pulmonale
• Endocrine disorders (DM, hypothyroidism,
hyperthyroidism)
• Infectious myocarditis
Angiotensin Pathway: Maintains BP , Volume & Osmolarity
Angiotensinogen, ANGI, ANG II, renin, & ACE

Figure 20-13: The renin-angiotensin-aldosterone pathway

 LV FILLING PRESSURE
(Pulmonary and/ or systemic
congestion)
A B.
WARM & DRY WARM & WET
Reduced
CO &
vasocon
striction L C
COLD & DRY COLD & WET
PROFIL A :
- Normal hemodynamic
- The symptoms are due to factors other than
cardiovasc
PROFIL B :
- Spesific for acute pulmonary oedema
- Profil C is more severe than B due to CO
disturbance
- Systemic vasoconstriction
- Profil B : therapy diuretic, vasodilator for lung
oedema
- Profil C : diuretic, vasodilator, inotropic
PROFIL L :
- Cold because of low output
- Congestif symptoms (-)
- Hipovolemia
pharmacologic management of HF is to modulate
the action of these
neurohumoral effectors

Goland DE, 2008

 Approach to the Patient with Heart Failure
Assessment of LV function (echocardiogram,
radionuclide ventriculogram)

EF < 40%

Assessment of
volume status

Signs and symptoms No signs and symptoms of

of fluid retention fluid retention

Diuretic ACE Inhibitor

(titrate to euvolemic state)
Digoxin
b-blocker
Effects of SNS Activation in Heart Failure

 Dysfunction/death of cardiac myocytes

 Provokes myocardial ischemia
 Provokes arrhythmias
 Impairs cardiac performance
These effects are mediated via
stimulation
of b and a1 receptors