Acute Coronary Syndrome Therapeutic Intervention

Acute Coronary Syndrome includes

1. Acute unstable angina pectoris
2. Acute myocardial infarction
These conditions are due to the formation of unstable artheromatous plaque with hematoma that leads to stenosis of the
blood vessels calliber. Blockage will then lead to ishceamic attack of the post stenotic tissue. This is therefore, through
emergency and prophylaxis therapeutic intervention, the aim of therapy is to
1. Immediate reperfusion of the ischeamic tissue
1. Fibrinolytics/Thrombolytics
1. Fibrin specific fibrinolytic agent (Tissue Plasminogen Activator)/Direct Fibrinolytic
1. Alteplase (tPA)
2. Non-fibrin specific fibrinolytic agent/Indirect Fibrinolytic
1. Streptokinase (SK) *a protein, not an enzyme
2. Prophylaxis of future ishceamic event
1. Antiplateletss
1. COX inhibitor
1. Aspirin
2. Adenosine Diphosphate (ADP) inhibitor
1. Clopidogrel
3. Additional Antiplatelet-Directed Drug
1. Dipyridamole
4. Glycoprotein IIb/IIIa inhibitor
1. Abciximab
3. Anticoagulant
1. Heparin
2. Warfarin

Fibrinolytics/Thromb

olytic Agents
1.

2.

All fibrinolytics can cause heamorrhage; to counteract by giving

1. Aminocaproic acid

2.

Tranxenamic acid
i. These agents bind to plasmin and hinders it from cleaving the fibrin

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Drug Name/ Infos
Streptokinase
Not an enzyme per se, but it elicits a
reponse like an enzyme
Protein that is derived from Beta
Hemolytic Streptococcus bacteria

Absolute contraindication

1.
2.
3.
4.

Prior or current heamorrhagic stroke

Intracranial neoplasm
Active internal bleeding
Aortic dissection

Fibrinolytic Agent/ Tissue Plasminogen

(tPA) (Indirect Fibrinolytic)
Pharmaceutical basis in choosing Activator
SK
Advantages
1. Relatively cheap
Disadvantages
1. It is not fibrin specific
a. Systemic bleeding may occur
2. Allergic reaction (bacterial product)
a.
b.

3.

Rash
Fever
Anaphylact
ic shock

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Drug Name/ Infos

Alteplase (tPA)

Mechanism of Action

1. Other than Urokinase, Plasminogen can also be activated through

endogenous Human Tissue Plasminogen Activator (tPA).
2. This enzyme, specifically cleaves fibrin bound Plasminogen instead of
free Plasminogen (like that of SK)
3. Due to hemodynamic instability presents in IHD patients, endogenous
tPA is not sufficient enough to fight against the fibrinogenesis.
This is therefore, human recombinant technology gives rise to
4.
Alteplase
Only be given IV
(cloned tPA) to be given to ACS in order to eleviate the action of tPA to
Distribution
as much as many folds.

Rapid onset
Through degradation of fibrin clot, reperfusion is positive in post
Highly effective when given within 3 hours 5. stenotic
after the onset of symptom
ischeamic tissues.
It is then indicated for
Metabolism
Extensively being metabolized by the liver 1. ST Elevated Acute Myocardial Infarction (STEMI)
Plasma t1/2 is about 5 minutes
2. Non-heamorrhagic stroke
Derived through a genetic engineering
by which human tPA is being engineered
through Human DNA Recombinant
technology
Pharmacokinetics
Adsorption

Excretion

Renal clearence

Adverse Effects
1.

Bleeding (less thant that of

SK)

Antiplatelet Agents
Cycloxygenase Inhibitor (COX Inhibitor)
Drug
Acetylsalicylate Acid
(ASPIRIN)
Pharmacological Effects
1. Anti-inflammatory
2. coagulation (the ONLY NSAIDs)
3. Anti-pyretic
4. Analgesia

Contraindication
1. Relative C/I
a
.
Bronchial asthma
i. Inhibit synthesis of PG
(bronchodilator)
2. Absolute C/I
a
.
Gouty arthritis
i. dose (anti-platelete)
1. No effect on uric acid renal
secretion
ii. Usual OTC dose
(analgesia/antipyretic)
1. Inhibits uric acid renal
secretion
iii. dose (Tx of RA)
1. Blocks reabsorption of uric
acid (uricosuric effect)
Children with influenza or
b. cold
i. Reyes syndrome
1. Potentially fatal
c. Pregnant ladies
rd
i. Antiplatelet effects on 3
trimester

Pharmacokinetic
Absorption
1. Best absorp in acidic condition
a. Its a weak acid in nature;
gastric environment is highly
acidic. Therefore aspirin will
remain unionized in the
stomach
b. Acidic drug tends to be lipid
soluble; readily being absorp
in through the GI mucosa
2. Most absorp at intestinal
mucosa due to high surface
area and low motility
Distribution
Hydrolyzes by esterases in
1. tissue
and blood by
a. Acetic acid
b. Salicylate
2. Salicylate is highly plasma
protein bound (albumin)
Metabolism
1. Hepatic metabolism
(conjugation)
a. Conjugate with glycine =
salicyluric acid
b. Conjugate with glucuronic =
salicyl acyl + phenolic
glucuronide
Excretion
1. Renal excretion through

Mechanism of
Action
1. Non-selective COX inhibitor, IRREVERSIBLY
inhibits
both
a. COX 1 (constitutional enzyme) which
coverts
arachidonic acid into
i. PGE2
1. Renal vasodilation
2. Bronchodilation
Inhibition of this will exarcebate
a. asthmatic
pts (relative contraindication)
ii. TXA2
1. platelete aggregation
a. Inhibition leads to anti-platelet activity
i. risk for AMI
ii. risk of CVA
PGI
iii. 2
1. gastric mucus secretion
a. Inhibition of this will reduce mucus
secretion, exarcebate gastritis
b. COX 2 (inducible enzyme) which converts
arachidonic acid into
Prostaglandins which
i.
involved in
1. Inflammation
a. Vasodilation (hypereamia)
b. capillary permeability (edema)
i. Inhibition will inflammation
2. Pain sensation
a. Directly binds to pain receptor and elicit
pain sensation (not visceral pain)
i. Inhibition will lead to analgesia
3. Pyrexia (fever)

Adverse Effects
1. Gastritis
a. Ion trapping inside
the gastric mucosa
b. Inhibition of PG12
synthesis mucus
secretion
c. Prophylaxis tx with
Misosprostol (PGE1
analogue)
2. Hepatotoxicity
3. Allergic action
a. Periorbital edema
b. Rash
Drug-drug Interaction
1. Warfarin
a. Due to its higher
affinity towards
albumin compared
to warfarin, aspirin
may displace
warfarin and lead
to in warfarin
toxicity

1. risk of bleeding
ii. PG prolongs labour
Therapeutic Uses
1. Fever
2. Ischeamic heart disease
3. Arthritis

a. Glomerular filtration
b. Tubular secretion
2. Highly sensitive to pH changes
3. Interfere with uric acid
excretion*

a. Prostaglandin together with IL-1b

stimulates thermostat at the OVLT to
increase temperature set point higher
than normal
i. Inhibition will return the temperature set
point to normal

Adenosine Diphosphate Inhibitor (ADP Inhibitor)

Mechanism of Action
Adverse Effects

Drug Name/ Infos

Clopidogrel (Plavix) 1. Clopidogrel is a non-competitive ADP receptor inhibitor, by 1. GI discomfort
Onset of action 1-2 days
Max effect 3-5 days

Drug Name/ Infos

Dipyridamole
1. Alone, less effective.
Always be given
together with
a. Dipyridamole + Aspirin
i. Cerebrovascular
accident
b. Dipyridamole +
Warfarin
i. Prevent
thrombogenesis in pts
with prothetic heart

which it will irreversibly block the ADP receptor and lead to

a. Nausea
these subsequent events:
b. Vomitting
a. Inhibits platelete aggregation
c. Constipation
b. platelets conformational change
2. Hardly cause neutropenia
c. release of platelet granules, which contained
compared to Ticlopidine
i. ADP
ii. TXA2
d. platelet amplification
2. Advantages of Clopidogrel over other antiplatelets
a. stroke and MI in pts with Coronary Arterial Disease
b. Better efficacy compared to aspirin eventhough relatively
expensive
c. rethrombosis after coronary artery stenting

Additonal Antiplatelet-Directed
Drugs
Mechanism of Action
Dipyridamole elicits response through numerous inhibitory
effects include
1. Inhibits Thromboxane Synthase
a. production of TXA2
b. TXA2, will instantly platelet aggregation
2. Inhibits the reuptake of Adenosine into the platelet
a. extracellular Adenosine level
b. platelet activation
3. Inhibits Phosphodiaesterase
a. conversion of cAMP to AMP
i. platelet resposne to ADP
b. conversion of cGMP to GMP

Adverse Effects
1.
2.
3.
4.

Fatigue
Flushing
Nausea
Headache

valves

2+

i. cGMP, intracellular Ca level

ii. Vasodilatory effect (Synergistic with Nitric Oxide)

Drug Name/ Infos

Abxicimab

Glycoprotein IIb/IIIa Platelet Membrane Receptor Blocker

Mechanism of Action
Adverse Effects

1. Glycoprotein IIb/IIIa complex is function as receptors on the 1. Bleeding

Chimeric monoclonal
platelet for
2. Thrombocytopenia
antibody of Glycoprotein a. Fibrinogen
IIb/IIIa platelet
b. Vitonectin
membrane receptor
c. Fibronectin
Main Clinical Uses
d. Von Willerbrand factor
1. Percutaneous
2. Activation of this receptor will complete the final common
Transluminal Coronary
pathway of fibrinogenesis (platelet aggregation)
Angioplasty (PTCA)
3. Abciximab is given through parenteral infusion in order to
therapeutic intervention
occupy the receptor, stopping the common ligands from
2. Unstable angina
activating the complex. This will therefore lead to
3. Non-STEMI
a. Blocks formation of fibrin
4. STEMI + Thrombolytics
b. Inhibits platelet aggregation
4. Receptor blockage activity is at about >80%