Professional Documents
Culture Documents
O2 supply O2 demand
Precipitating factors
ISCHEMIA
PAIN
S D
Age Hypertension
Smoking Hypercholesterolemia
DM Oral contraception
Genetic ?
atherosklerosis
OBSTRUCTION (a.coronary)
Decreased 02 supply
1. O2 supply to the tissue
2. O2 demand of the tissue
3. risk factor
Three major classes of agents are used individually or
in combination to treat angina:
1. Organic nitrates:
Vasodilate coronary arteries
Reduce preload and aferload
3. Beta-adrenergic blockers:
Decrease heart rate and contractility - decrease in cardiac
work and O2 consumption
Improve myocardial perfusion due to decrease in heart rate –
decreased in ventricular wall tensi
1. Nitrates
a) Short acting (10 minutes): Glyceryl trinitrate (GTN and Nitroglycerine) -
EMERGENCY
b) Long acting (1 Hour): Isosorbide dinitrate, Isosorbide mononitrate
Guanylate Cyclase*
converts
GTP
cGMP
activates
• Plasma clearance:
NG: 50L/min
IDN: 4L/min
ISMN: 0.6L/min
• Indikasi:
– Angina stabil
– Angina tidak stabil
– Angina Variant
• Serangan akut: Nitrat kerja cepat (sublingual, iv)
• Terapi kronik: Nitrat kerja sedang/lambat (oral,
transdermal)
– Gagal jantung kongestif
– Infark miokard
Efek samping
• Hati-hati pada:
– Peningkatan tekanan intrakranial
– Hipotensi, hipovolemia
– Takiaritmia
– Kombinasi dengan vasodilator lain
Continuous or frequent exposure to nitrates can lead to the
development of complete tolerance
The mechanism of tolerance is not completely understood:
May be related to the enzymes involved in converting the nitrates to
NO
or to the enzyme that produces cGMP
Industrial (occupational) exposure to organic nitrates has been
associated with “Monday disease” and physical dependence
manifest by variant angina occurring 1-2 days after withdrawal
NITRAT ORGANIK
• Amilnitrit:inhalasi
• Nitrogliserin: oral, parenteral, spray, transdermal
• Isosorbid mononitrat (ISMO): oral
• Isosorbid dinitrat (ISDN): oral
• Penta eritritol tetra nitrat: oral
Drug Usual single dose Route of Duration of action
administration
Short acting 0.15-1.2 mg sublingual 10 - 30 min
Nitroglycerin
Isosorbide dinitrate 2.5-5 mg sublingual 10 – 60 min
Amyl nitrite 0.18 – 3 ml inhalation 3 – 5 min
Long acting
Nitroglycerin sustained 6.5 – 13 mg q 6-8 hrs oral 6 – 8 hrs
action
Nitroglycerin 2% 1 – 1.5 inches q hr topical 3 – 6 hrs
ointment
Niroglycerin slow 1 –2 mg per 4 hrs Buccal mucosa 3 – 6 hrs
released
Nitroglycerin slow 10 – 25 mg /24hrs (one transdermal 8 –10 hrs
released patch/day}
Isosorbide dinitrate 2.5 – 10 mg per 2 hrs sublingual 1.5 – 2 hrs
1. Golongan dihidropiridin
Nifedipin, nicardipin, nimodipin, felodipin, amlodipin, nitrendipin, lacidipin
2. Golongan fenilalkilamin: Verapamil
3. Golongan benzotiazepin: Diltiazem
Mekanisme kerja:
Menghambat masuknya kalsium ke dalam sel
Pembuluh darah: Vasodilatasi
Miokard: inotropik negatif
Nodus SA, nodus AV: kronotropik, dromotropik negatif
CCB
O2 demand O2 demand
CCB
• VERAPAMIL – DILTIAZEM
– Efek langsung:
• Inotropik, kronotropik (-) kebutuhan O2 miokard
– Efek tak langsung:
• Inotropik (-) tegangan dinding ventrikel
• Kronotropik (-) waktu pengisian arteri koroner
Though most beta-blockers do not cause coronary vasodilatation
like the nitrovasodilators or calcium channel blockers, beta-
blockers are important in the treatment of angina because of
their effects on the heart
• Efek langsung:
– Kronotropik & inotropik negatif menurunkan kebutuhan O2 miokard
• Efek tak langsung:
– Inotropik (-) mengurangi tegangan dinding ventrikel
– Kronotropik (-) memeprpanjang waktu diastol pegisian a.
koroner (suplai )
• Indikasi: Angina stabil kronik
Is the prototype adrenergic blocker
Inotropic
chronotropic O2 demand
Adrenergic domotropic
blocker
Renin Ag peripheral BP
resistance
aldosteron
Sodium, water BP
retention
•Antiplatelet (antitrombosit)
•Antikoagulan
•Fibrinolitik (trombolitik)
ANTIPLATELETS, ANTICOAGULANT,
THROMBOLYTIC
• Antiplatelets:
– Drugs that prevent platelet adhesion, activation,
and aggregation
• Anticoagulants:
– Drugs that prevent blood coagulation cascade
through modification of coagulation factors
• Thrombolytics/ fibrinolytics:
– Drugs that degrade the thrombus
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ANTIPLATELET
• Platelet:
ADP-receptor
Glycoprotein
IIb/IIIa:
Dense Particle:
fibrinogen
ADP, Thromboxane
receptor
A2, serotonin
Receptor of v WF(Gp Ib
receptor) collagen
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Platelet activation:
Platelet adhesion
Injured endothelium releases von Willebrand factor
(collagen receptor)
Platelet activation by:
Thrombin, ADP, serotonin, thromboxane A2
Activation of receptors on platelet surface:
TxA2 receptor, ADP-receptor, Glycoprotein IIb/IIIa receptor
(fibrinogen receptor)
Platelet aggregation
Linking of platelet by fibrinogen
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PLATELET ACTIVATION
39
1. Inhibitor of Cyclooxygenase: ASPIRIN
AA ------------ Thromboxane-A2
COX
40
2. ADP-receptor blockers:
Ticlopidin
Reduce platelet activation by ADP
No gastric irritation
Side effects: neutropenia, liver abnormalities, thrombotic
thrombocytopenia
Clopidogrel
Less side effects, but costs much more
Faster onset of action
Less GI adverse effects
Now become standard therapy in acute coronary syndrome.
41
3. Gp IIb/IIIa receptor blockers:
abciximab, eptifibatide, lamifiban, tirofiban
Prevent the final step in platelet aggregation
To be administered Intravenously
Only for limited time and not routinely used
Contraindication
Active bleeding or potentially bleeding
Thrombocytopenia
42
Heparine routinely used in ACS
Unfractionated heparine (UFH)
Low molecular weight heparine (LMWH):
Fraxiparine, nadroparine, enoxaparine, dalteparine …
Synthetic pentasaccharide: Fondaparinux
Mechanisms of action:
Binds to antithrombin inactivate of F Xa and F IIa.
Fondaparinux inactivate F Xa only
43
Should be administeed parenterally (iv, sc)
UFH need monitoring of effects (aPTT)
LMWH & fondaparinux: no needs of aPTT monitoring
LMWH & fonaparinux have a longer half life once
or twice daily
Do not cross placental barrier safe for pregnant
women
Antidote of heparine toxicity: Protamine sulphate
44
Side effects
Bleeding
Thrombocytopenia
Contraindication
Active bleeding, haemophilia, severe hypertension,
intracranial hemorrhage, advance hepatic or renal
disease, threatened abortion …
45
Warfarin, dicumarol
vitamine K antagonist inhibits activation of
vit K-dependent factors (II, VII, IX, X)
Delayed onset of action
Administered orally (rarely iv)
Need monitoring of prothrombin time (INR)
Target: INR 1.5 – 3.5 of normal level (reduction
of PT by 25%)
46
Warfarin crosses placental barrier readily
hemorrhagic and malformation of the
fetus contraindicated during pregnancy
Rarely: cutaneous necrosis, infarction of
the breast, fatty tissues, intestines,
extremities.
Interact widely with other drugs (NSAID,
vit K, barbiturates, rifampicin, diuretic,
steroids, sulpha, amiodarone, …) and
foods
Antidote: Vit K
47
48
Streptokinase Fibrinogen
Urokinase
Anistreplase Thrombin
Alteplase (tPA)
Fibrin
Plasminogen Plasmin
FDP
49
Thrombolytic is only effective in newly formed
thrombus (Less than 6-12 hours)
Administration: iv infusion
STREPTOKINASE
Produced by Steptococcus
UROKINASE
Extrated from human renal cells allergic rx/ rare
ALTEPLASE (tPA)
Naturally occuring fibrinolytic
50
Side effects:
Hemorrhage
Hypotension (Streptokinase)
Allergic reaction (Streptokinase)
Contraindications
Active bleeding
Any previous history of hemorhagic stroke
Non hemor. Stroke within 1 year
Internal bleeding within 6 mo.
Hypertension (>180/110), pregnancy
Major surgery, trauma
Pregnancy
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