Drugtherapy for

ANGINA PECTORIS - CAD

Ngatidjan, MD., M.Sc., Sp.FK.

Department of Pharmacology and Toxicology

07/10/2004
Faculty of Medicine GMU
Ngatidjan, OBAT ANGINA-CAD 1
Angina pectoris
Manifestation of myocardial ischemia

caused by imbalance of

* myocardial oxygen demand

* and coronary blood supply

07/10/2004
relatively decrease of oxygen
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Angina pectoris

caused by

- coronary spasm

- occlusion of coronary blood vessel

(partially) thrombus

totally
07/10/2004 myocardial infarction
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Angina pectoris
1. Acute angina pectoris (exercise, spasm, emboli)
2. Stable angina pectoris
(exercise - atheroma predictable)
3. Unstable angina pectoris
(resting embolus myocardian infarction)
4. Varian Prinzmetal angina pectoris
(coronary spasm)
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Therapy of ANGINA PECTORIS

- increase coronary blood flow

coronary vasodilators

- decrease myocardial oxygen demand

decrease heart contraction (b-blockers and Ca2+ antag.)

- antithrombus (aspirin, heparin)

(for unstable angina)
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drugs for ANGINA PECTORIS

- Nitrate dan nitrite

0 isosorbide dinitrate)
(amilnitrite, nitroglyserine,

- Calcium antagonists
0
(verapamil, diltiazem, nifedipin)

- b-blockers (acebutolol, atenolol, propranolol)

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Nitrate and nitrite
- increase intracellular cAMP vasodilatation

0
- coronary vasodilatation
increase coronary blood supply
0
- dilatation of venule
. veneous return end diastolic pressure

. cardiac dilatation

07/10/2004
heart contraction
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O2 demand 7
 NITRATE - NITRITE
nitrate - nitrite

vasodilatation vasodilataion
of coronary blood vessel of arteriole and venule

oxygen supply venous return

heart contraction

oxygen demand
07/10/2004 angina
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Nitrate - nitrite
- side effects
. Headache 0
. Flushing
0
. Orthostatic hypotension

. Tachycardia (reflectory)
07/10/2004 worsening of the angina pectoris
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Nitrate - nitrite
- To reduce side effects
. begin from small0dose (MED)
. sitting position when taking the drugs
0
standing postural hypotension tachycardia

lying down veneous return

cardiac work load worsening of angina

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 CALCIUM ANTAGONISTS

Calcium antagonists

heart contraction and vasodilatation

oxygen demand and blood supply

07/10/2004 angina
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 b-blockers (acebutolol, atenolol, dsb.)
b-blockers

heart contraction

oxygen demand

angina
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 b-blockers (acebutolol, atenolol, dsb.)
b-blockers
- cardioselectivity (asthma bronchial, DM)

- ISA - positive (partial agonist) ----- bradycardia

- triglyseride
- HDL atherosclerotic risk
LDL
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 ACETOSAL (R)
(Aspirin )

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 arachidonic acid

Cyclooxygenase lipooxygenase

PGH2 5-HETE

isomerase Prostacycline Tx-synthetase Leukotriene A4

synthetase
(LTA4)
PGE2 PGI2 TxA2
(Prostaglandins) (Prostacycline) (Thromboxane)
- PG2a - PGI2 - TxA2
- PGD2 - PGF1a - TxB2 LTC4 LTB4
- PGF2a Aggregasi trom.
- HHT blood clotting
(bronchoconstriction
- inhibit HCl secretion LTD4
- stimulate mucosal protective mucous secretion
- 07/10/2004
prevent gastric ulcer Ngatidjan, OBAT ANGINA-CAD pseudoallergy 15
 physiological stimuli inflamatory stimuli
(heat, mechanical, chemical)

COX1 COX2
constitutively present in many tissues) inducible amount markedly
in response to inflamatory
mediators

TX-A2 PGE
(platelet functions) (renal functions)
proteases, PGs
prostacyclin and other inflamatory
mediators
- gstroprotective
- antithrombotic properties
of vascular endothelium
inflamation
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 COX1
constitutively present in many tissues)

TX-A2 (Thrombocyte) PGE

(platelet aggregation) (renal functions)

Prostacyclin (endothelial cell)

- gstroprotective
- antithrombotic properties
(inhibit pletelet aggregation)

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 COX1
constitutively present in many tissues)

acetosal
TX-A2 (Thrombocyte) PGE
(platelet aggregation) (renal functions)

low concentration Prostacyclin (endothelial cell)

of acetosal - gstroprotective
- antithrombotic properties
(inhibit pletelet aggregation)
high concentration
07/10/2004 of acetosal
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 Acetosal (acetyl salicylic acid)
- inhibit TX-A2 synthesis (ASA)
antithrombus effect (in low dose)
(prehepatic effect)
- inhibit Prostacyclin synthesis
thrombolytic effect (in high dose)
(post hepatic systemic effect)

low dose ASA for antithrombus

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 Acetosal (acetyl salicylic acid)
Side effects
1. Epigastric dyscomfort
(gastric iritation)
2. Gastrointestinal bleeding (melena)
3. Prolonged bleeding timesyndrome)

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Heparin
Pharmacolocical effects
1. Bind to antithrombin III
(prevent coagulation)
2. Protein bind : 95 99%
3. Is not absorbed by g.i. tract
intraveneous injection
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Heparin
Side or adverse effects
1. Haemorrhage
2. Osteoporosis
3. Hypersensitive reaction
4. Paradoxal effect : thrombosis
(though IgM and IgG antibody complex)
vasculopathy
07/10/2004 DIC
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