Lecture 9
Anti-platelet
Learning objectives
★ describe different classes of anti-platelet drugs
and their mechanism of action
★ understand pharmacological effects,
pharmacokinetics, clinical uses and adverse ▪ Additional Notes
effects of anti-platelet drugs ▪ Explanation –Extra-
▪ Important
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before starting, please check our GIT block correction
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Clot
Platelets and vessels THROMBUS: is the CLOT that adheres to
In healthy vessels, nitric oxide and vessel wall.
prostacyclin (released by endothelial EMBOLUS: is the CLOT that floats in the
cells lining the blood vessels) inhibit blood.
platelets aggregation. (vasodilator ) THROMBOSIS: is the formation of
unwanted clot within the blood vessel,
Damage to the vessel wall leads to producing life threatening conditions such
interaction between Platelets, as:
Endothelial cells and Coagulation factors Acute myocardial infarction (MI)
which lead to formation of the CLOT Acute ischemic stroke
Deep vein thrombosis (DVT)
Pulmonary embolism (PE)
The role of platelets in hemostasis
Adhesion Activation
- Following vascular injury, von Willebrand factor
binds to collagen in the exposed
-Following adhesion, agonists such as collagen,
subendothelium at the site of injury.
thrombin, adenosine diphosphate (ADP), and
- The other site of the “rod-formed” von
thromboxane A2 activate platelets by binding to
Willebrand factor binds to the platelet receptor
their respective platelet receptors.
GPIb and platelets are thereby anchored to the
site of the injured endothelium. This is called
adhesion.
The role of platelets in hemostasis
Activation Aggregation
- As a result of agonist binding, platelets undergo
The third step of platelet response is
a shape change and new structures such as
aggregation. After activation, binding of
phospholipids and GPIIb/IIIa receptors are
fibrinogen to GPIIb/IIIa causes platelets to
exposed on the cell membrane. This is called
.adhere to each other into a loose platelet plug
activation.
Drugs used in thrombosis
Anticoagulants: drugs which prevent clotting by inhibiting clotting factors (coagulation process)
(used in prevention and treatment of thrombosis).
ﯾﻤﻨﻌﻮا وﺻﻮل اﻟﺠﻠﻄﺔ ﻵﺧﺮ ﻣﺮﺣﻠﺔ.
Antiplatelets: drugs which prevent and inhibit platelet activation and aggression (used as
prophylactic therapy in high risk patients).
Thrombolytics or Fibrinolytics: act by dissolving existing or already formed thrombi or emboli
and used in the acute treatment of thrombosis.
Classification of antiplatelet drugs:
Arachidonic acid Phosphodiesterase Glycoprotein
ADP inhibitors
pathway inhibitors inhibitors IIb/IIIa inhibitors
Ticlopidine - Abciximab – Eptifibatide
Aspirin Dipyridamole .
Clopidogrel -Tirofiban
ADP pathway inhibitors
Arachidonic acid pathway inhibitors
Ticlopidine & Clopidogrel
( Aspirin ) Acetylsalicylic Acid
● These drugs specifically and irreversibly
● Irreversible inhibition of cyclooxygenase inhibit ADP receptor of subtype P2Y12,
enzyme ( COX-1 ) via acetylation. which is required for platelets activation
Mechanism ● Small dose inhibits thromboxane (TXA2) thus prevent platelet aggregation.
of action
synthesis in platelets But not prostacyclin P2Y12 is purinergic receptor and is a
(PGI2) synthesis in endothelium (larger chemoreceptor for adenosine diphosphate
dose). (ADP).
● Risk of peptic ulcer. ● Sever neutropenia, (CBC should be done
Side monthly during treatment.)
● Increased incidence of GIT bleeding (aspirin
effects ● Bleeding ( prolong bleeding time ).
prolongs bleeding time) ● G.I.T : nausea, dyspepsia, diarrhea.
● Allergic reactions.
Arachidonic acid pathway inhibitors ADP pathway inhibitors
( Aspirin ) Acetylsalicylic Acid Ticlopidine & Clopidogrel
● Prophylaxis of thromboembolism e.g. ● are given orally.
prevention of transient ischemic attack, ● have slow onset of action (3 - 5 days).
ischemic stroke and myocardial infarction. ● pro-drugs, they have to be activated in the
● Prevention of ischemic events in patients liver.
with unstable angina pectoris. ● bound to plasma proteins
uses
● can be combined with other antiplatelet
drugs (clopidogrel) or anticoagulants Clinical Uses of ADP inhibitors
(heparin). ● Secondary prevention of ischemic
● Dose: Low-dose aspirin ‘’baby aspirin’’ (81 complications after myocardial infarction,
mg enteric coated tablet/day ) is the most ischemic stroke and unstable angina.
common dose used to prevent a heart
attack or a stroke. (Secondary prevention : means he had no
thrombus, but he could have it).
(Primary prevention : he had cured from
thrombus and this for prevention from another
thrombus) .
Clopidogrel
Coronary angioplasty (percutaneous
Indications: coronary intervention, PCI) is a
✧is more potent than ticlopidine ✧For patients with a history procedure used to open clogged heart
✧Longer duration of action than of recent myocardial arteries. Angioplasty involves
ticlopidine infarction (MI), recent temporarily inserting and inflating a
✧ Less frequency of stroke, or established tiny balloon to help widen the artery.
administration (given once daily peripheral arterial disease.
). ✧For patients with acute
✧Less side effects (less coronary syndrome
neutropenia). (unstable angina/ MI): either
✧Bioavailability is unaffected by those managed medically or
food. with percutaneous coronary
✧ Clopidogrel has replaced intervention ( PCI ) with or
ticlopidine without stent.
acute coronary syndrome = unstable
angina with MI
New ADP Pathway Inhibitors
Prasugrel Ticagrelor
Irreversible inhibitor of the P2Y12 receptor Reversible inhibitor of the P2Y12 receptor
-both have more rapid onset of action than clopidogrel
-both drugs do not need hepatic activation (are not prodrugs)
Uses:
to reduce the rate of thrombotic cardiovascular events (including stent thrombosis) in patients with
acute coronary syndrome who are to be managed by PCI.
Adverse effects:
-both increase bleeding risk -Ticagrelor causes dyspnea
Glycoprotein IIb/ IIIa receptor inhibitors
Tirofiban & Eptifibatide:
✻Tirofiban (non-peptide drug)
Abciximab:
✻Epitafibatide (peptide drug)
✻MOA: inhibits platelet aggregation by preventing
the binding of fibronigen, von Willebrand factor, ✻MOA: Act by occupying the site on glycoprotein
and other adhesive molecules to GPIIb/IIIa receptor IIb/ IIIa receptor that is required to bind the
sites on activated platelets
platelet to fibrinogen ( act as fibrinogen- mimetic
✻Given I.V. infusion.
agents ).
✻is used with heparin and aspirin as adjunct to
PCI* for the prevention of cardiac ischemic ✻They are given intravenously for the reduction of
complications. incidence of thrombotic complications during
*percutaneous coronary intervention
coronary angioplasty (PCI)
★ Note that Glycoprotein IIb/ IIIa receptor is required for platelet aggregation with each others and
with fibrinogen and von Willbrand factor.
Dipyridamole
It is a vasodilator and antiplatelet
MOA:
Inhibits phosphodiestrase thus increases cAMP causing decreased synthesis of thromboxane A2
and other platelet aggregating factors.
Phosphodiesterase enzymes that normally break down cAMP
Uses of dipyridamole
✴Given orally.
Adverse Effects:
✴Adjunctive therapy for prophylaxis of
thromboembolism in cardiac valve replacement (with
-Headache
warfarin). -Postural hypotension
✴Secondary prevention of stroke and transient
ischemic attack (with aspirin).
Mechanisms of action
of antiplatelet drugs
Summary
MCQs
1)A 45- year-old male who came
3)Which one of these drugs is
to the ER with MI and
underwent PCI. From history, he reversible inhibitor of the
is on phenytoin. Which is the P2Y12 receptor:
best protective drug to give in A-ticlopidine
this case ? B-Prasugrel
A- Prasugrel C-Ticagrelor
B- ticlopidine
C- clopidogrel 4) Drug is given by I.V :
A-Tirofiban
2)A 55-year- old male came to B-Ticagrelor
GP with severe abdominal pain C-Dipyridamole
after meals & hyperacidity .
Endoscopy shows gastric ulcer.
From history, he is a heavy 5)one of Dipyridamole side
smoker for 25 years and taking effect is :
drug A as cardio protection.
A- peptic ulcer 1)A
What’s drug A that can be the
cause of his illness ? B- hypertension 2)B
A- dipyridamole C- postural hypotension 3)C
B- aspirin 4)A with gratitude
C- abciximab
5)C for team 433
SAQs
1) What is the Mechanism of Aspirin ?
Irreversible inhibition of cyclooxygenase enzyme ( COX-1 ) via acetylation..
2) What is the indications for Clopidogrel ?
recent myocardial infarction (MI)
recent stroke
established peripheral arterial disease.
acute coronary syndrome
3)Name the ADP inhibitor which causes dyspnea .
Ticagrelor
4) What is the difference between abciximab and Tirofiban ?
binding to all GPIIb/IIIa receptor sites on activated platelets.
bind the platelet to fibrinogen on glycoprotein IIb/ IIIa receptor .
Good luck!
Done by Pharmacology team
★ Rana Albarrak
★ Mona Al-Qahtani
For any correction, suggestion or any useful information do not hesitate to contact
us: Pharmacology434@gmail.com
