Overview of antiplatelets

1. Antithrombotic
agents 1
Dr. Su Mon Thwe

2. Damaged vessels
Platelets
- Adhesion
- Aggregation
Coagulation system activation
- Fibrin
Antiplatelet
Anticoagulant
Fibrinolytic

3. Emerging Therapies for Acute Coronary Syndromes - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Mechanism-of-acute-coronary-
syndromes-and-targets-of-anti-platelet-and-anti-thrombotic_fig3_51746615

4. ANTIPLATELET
more effective for
arterial clots that
are composed
mainly of platelets
(white clot)
ANTICOAGULANT
most effective for venous
thrombosis and that
associated with sluggish
blood flow (red clot)
FIBRINOLYTIC AGENT
Lysis of formed
thrombus 
recanalisation
For Prevention & Treatment of Thrombosis
Antithrombotic Agents

5. Antiplatelets

6. • A 62-year-old man presents to his primary care physician with a 4-month history of pain in his lower legs. He
reports experiencing pain after he walks for a sustained period of time but is concerned that the distance. he is
able to walk has decreased over time. He now feels the pain even when walking around a shopping mall. The
pain resolves completely with rest. His medical history includes hyperlipidemia, hypertension, and diabetes.
Medications include atorvastatin, lisinopril, and metformin. Allergies include penicillin and aspirin. He
previously took another drug but discontinued it because he developed thrombotic thrombocytopenic purpura.
His blood pressure is 131/82 mmHg, pulse is 77/min, and respirations are 14/min.
• Which drug will be prescribed to this patient?
• What is the mechanism of the drug that should be given to this patient?
a) Adenosine diphosphate receptor antagonist
b) Glycoprotein IIb/IIIa receptor antagonist
c) Irreversible inhibitor of cyclooxygenase
d) Phosphodiesterase III inhibitor
e) Vitamin K epoxide reductase inhibitor

7. Platelet
Activation
Platelet
Aggregation
Platelet
Adhesion

8. Irreversible
Clopidogrel
Prasugrel
Ticlopidine
Reversible
Ticagrelor
Cangrelor
Gp IIb/IIIa receptor antagonist
Abciximab
Eptifibatide
COX-2
PG I2
Inhibit platelet
adhesion
PDE
cAMP
cAMP breakdown
vessel
Vorapaxar blocks PAR-1 receptors to prevent thrombin
action on the platelet

10. Aspirin

11. COX-2
PG I2
Inhibit platelet
adhesion
PDE
cAMP
cAMP breakdown
vessel

12. Aspirin
(low dose/ subanalgesic dose)
Primary & secondary prevention of complications of atherosclerotic disease
• Angina
• Myocardial infarction
• Stroke
• Peripheral vascular disease

13. Untoward effect of aspirin
• Salicylate sensitivity
• Bleeding (active PU, uncontrolled hypertension, severe renal or hepatic insufficiency,
haemophilia, pregnant)
• Anaemia, hypoprothrombinaemia, thrombocytopenia
• GI irritation, dyspepsia, nausea, vomiting
• Bronchospasm, worsen the control of intrinsic asthma
• Reye's syndrome (rare). Avoid using it in children < 16 years

14. Aspirin

15. Aspirin

16. 17
Allergen
Activated B cell Mast cell
Immediate phase Late phase
Degranulation
Histamine
Leukotrienes
Leukotrienes
Adenosine
IL3, IL5, IL8
Toxic proteins
Progressive inflammatory reaction
Bronchospasm
Bronchospasm
Mucous production
Mucosal edema
T cell
B cell
IL-13 IL-4
5/11/20
Pathophysiology
of asthma

17. Untoward effect of aspirin
• Salicylate sensitivity
• Bleeding (active PU, uncontrolled hypertension, severe renal or hepatic insufficiency,
haemophilia, pregnant)
• Anaemia, hypoprothrombinaemia, thrombocytopenia
• GI irritation, dyspepsia, nausea, vomiting
• Bronchospasm, worsen the control of intrinsic asthma
• Reye's syndrome (rare). Avoid using it in children < 16 years

18. Contraindications of aspirin
• Hypersensitivity to aspirin or other NSAIDs
• Peptic ulcer, haemorrhagic disease, coagulation disorder (e.g. haemophilia,
thrombocytopenia), Gout
• Severe hepatic and renal impairment
• Children <16 years and recovering from viral infection
• Pregnancy (doses >100 mg daily during 3rd trimester) and lactation
• Patients with G6PD deficiency

19. Dosage of aspirin
• Acute ischaemic stroke, Angina pectoris, Myocardial infarction
For primary prevention: Loading: 150-300 mg.
• Prophylaxis of cardiovascular events in high-risk patients
Long term: 75-150 mg once daily. Short term: 150-300 mg daily.
Administration: Should be taken with food.
Enteric-coated/modified-released, swallow it whole. Do not divide, chew or crush the tablet.

21. • For antiplatelet action: small daily dosages (75 mg daily)
• Once started appropriately – lifelong treatment
• Control BP before starting an antiplatelet drug (uncontrolled hypertension ↑ risk
of bleeding on aspirin)
• Early treatment with aspirin in patients with myocardial infarction saves as many
lives as thrombolysis
Prescribing information

22. DDI of aspirin
Other antiplatelet, Warfarin
↑ risk of bleeding
Balance risk vs benefit
Diuretics
Antagonize the diuretics action
(with high dose of aspirin)
NSAID (Ibuoprofen)
Interfere antiplatelet action of
aspirin
Methotrexate ↓excretion of methotrexate,
↑ risk of toxicity

23. Oral P2Y12 inhibitors

24. Oral P2Y12 inhibitors
• Block platelet P2Y12 receptor, key role in platelet activation & amplification of arterial
thrombus formation
Irreversible
Clopidogrel
Prasugrel
Reversible
Ticagrelor
Cangrelor

25. Clopidogrel
Indication:
• unable to tolerate Aspirin, hypersensitivity to aspirin
• acute coronary syndromes - Aspirin + Clopidogrel
• first 28 days following PTCA (percutaneous transluminal coronary
angioplasty) - Aspirin + Clopidogrel
• less GI irritation

26. Untoward effects
• Hypersensitivity (rash, angioedema, haematologic reaction);
• prolonged bleeding time
• Blood: Thrombocytopenia, leucopenia, eosinophilia, neutropenia
• Haematuria, Epistaxis, Bruising, pruritis, Haematoma.
• GI: Diarrhoea, abdominal pain, dyspepsia, gastric ulcer, duodenal ulcer, gastritis,
vomiting, nausea, constipation, flatulence (less GI irritation than aspirin)
• Headache, paraesthesia, dizziness
• Potentially Fatal: Rarely, thrombotic thrombocytopenic purpura, intracranial
bleeding, gastrointestinal and retroperitoneal haemorrhage

28. Drugs that inhibit CYP2C19, such as omeprazole may reduce the action of clopidogrel
3/29/2024 Dr. SMT 29
Others CYP2C19 inhibitors
- fluvoxamine, moclobemide
- voriconazole
- ticlopidine
- Carbamazepine
- efavirenz)
DDI
prodrug
Antiplatelet effect

29. Clopidogrel dosage
• Acute coronary syndrome (STEMI, NSTEMI, Unstable angina)
• ≤75 years
• 300 mg loading dose, followed by 75 mg o.d. (in combination with aspirin).
Initiate combined treatment as early as possible after symptoms start and
continue for at least 4 weeks.
• Elderly: >75 years
• 75 mg o.d. (without a loading dose)
• Prophylaxis of thromboembolic disorder
• For patients with recent MI, recent ischemic stroke, or established peripheral
arterial disease: 75 mg o.d.
• For patients with atrial fibrillation who have at least 1 risk factor for vascular
events, are not suitable for vitamin K antagonist treatment, and have low
bleeding risk: In combination with aspirin: 75 mg o.d.

30. Prasugrel
• Greater antiplatelet effect – More rapid onset, greater potency & superior to clopidogrel
• more predictable
• Not susceptible to drug interactions
• Greater efficacy than clopidogrel (in patients with ACS + PCI) (A+P > A+C)
3/29/2024 Dr. SMT 31
Acute coronary syndrome
Adult: 60 mg loading dose, followed by 10 mg o.d. for up to 12 mth, given in combination w/ aspirin.
Elderly: ≥75 yr Maintenance: 5 mg o.d.
Patient w/ low body wt (<60 kg): 5 mg o.d. as maintenance dose

31. Ticagrelor
- More rapid onset, greater potency & superior to clopidogrel
- More rapid & predictable off set of action compared with clopidogrel
- Greater efficacy than clopidogrel (in patients with ACS ) (A+T > A+C)
3/29/2024 Dr. SMT 32

32. Clopidogrel Prasugrel Ticagrelor
• Acute coronary syndrome
• Prophylaxis of
thromboembolic disorder
- recent MI
- recent ischemic stroke, TIA
- established peripheral
arterial disease
- AF
• Acute coronary syndrome • Acute coronary syndrome
• Minor ischemic stroke (NIHSS
score ≤5)
• high-risk TIA (ABCD2 score
≥4) [Oral: Initial: 180 mg once in
combination with aspirin, followed by 90
mg twice daily in combination with aspirin
for 30 days]
Indications

33. Clopidogrel Prasugrel Ticagrelor
Active pathological bleeding,
including peptic ulcer or
intracranial hemorrhage
Hypersensitivity (eg, anaphylaxis)
to clopidogrel or any component
of the product
Active pathological bleeding,
including peptic ulcer and
intracranial hemorrhage
Hypersensitivity (eg, anaphylaxis)
to prasugrel or any component of
the product
Previous stroke or TIA;
discontinue if stroke or TIA occurs
with therapy
History of Pathological bleeding,
active (eg, peptic ulcer or
intracranial hemorrhage)
Hypersensitivity (eg, angioedema)
to ticagrelor or any product
component
Severe hepatic impairment Severe hepatic impairment (Child-
Pugh class C)
Severe hepatic impairment
Contraindications
• All P2Y12 inhibitors should be used with caution in patients at high risk of bleeding or with significant anaemia

34. GP IIb/IIIa receptor Antagonists

35. Gp IIb/IIIa receptor antagonist
Abciximab
Eptifibatide
COX-2
PG I2
Inhibit platelet
adhesion
PDE
cAMP
cAMP breakdown
vessel
Monoclonal Antibody Fab fragment

36. • Route: IVI (under specialist supervision)
• Indication (NICE)
• Patients with high-risk unstable angina or non-Q-wave myocardial infarction
• As an adjunct to PTCA if:
• the procedure is indicated but delayed.
• the patient has diabetes mellitus.
• the procedure is complex.
• monitored closely in a coronary care unit
• Measure – PT, APTT, Platelet count (4 & 24 hours), Hb & HcT (12 & 24 hours)
• Stop the infusion if emergency surgery or arterial balloon pump insertion is required
• It can take ≥12 hours for platelet function to be restored after stopping the infusion

37. PDE inhibitors

38. COX-2
PG I2
Inhibit platelet
adhesion
PDE
cAMP
cAMP breakdown
vessel

39. Dipyridamole (Persantin)
• dose related effect
• effective only when used together with
warfarin or aspirin
• Use
• Secondary prevention of stroke following
stroke or TIA (modified-release cap: 200 mg
bid)
• for prophylaxis of thromboembolism
associated with prosthetic heart valves -
adjunct to oral anticoagulant
• Untoward Effects - headache
inhibits phosphodiesterase
 cAMP
 platelet adhesion

40. Cilostazol
• Antiplatelet action + Vasodilator
• Use
• Intermittent claudication: Oral: 100 mg b.d., when
refractory to exercise therapy & smoking
cessation; use in combination with either aspirin
or clopidogrel
• Secondary prevention of non-cardioembolic
stroke or TIA (off-label use) Oral: 100 mg b.d.
(Clopidogrel or aspirin/extended-release
dipyridamole recommended over the use of
cilostazol)
inhibits phosphodiesterase III
 cAMP
 platelet
adhesion
Direct
arterial VD

41. Untoward effects
• Significant: Tachycardia, palpitation, tachyarrhythmia, hypotension,
thrombocytopenia, leucopenia, agranulocytosis
• Angina pectoris, ventricular extrasystoles
• nausea, vomiting, diarrhoea, dyspepsia, flatulence, abdominal pain, abnormal faeces
• Asthenia, anorexia
• Oedema (peripheral, face)
• Headache, dizziness
• Rhinitis, pharyngitis
• Ecchymosis, rash, pruritus
• Potentially Fatal: Rarely, pancytopenia, aplastic anaemia

42. Ozagrel

43. COX-2
PG I2
Inhibit platelet
adhesion
PDE
cAMP
cAMP breakdown
vessel

44. Ozagrel
 inhibits synthesis of thromboxane A2  ↓platelet aggregation
 ↑production of prostacyclin
• improves the balance between prostacyclin & TXA2
• inhibitory action on cerebrovascular spasm
• For improvement of cerebral vasospasm after operation for SAH & its resultant
ischemic symptoms; motor dysfunction resulting from cerebral artery thrombosis
(acute phase)
• Route: IV infusion

45. Irreversible
Clopidogrel
Prasugrel
Ticlopidine
Reversible
Ticagrelor
Cangrelor
Gp IIb/IIIa receptor antagonist
Abciximab
Eptifibatide
COX-2
PG I2
Inhibit platelet
adhesion
PDE
cAMP
cAMP breakdown
vessel

46. Dual Antithrombotic Therapy
(DATT)
Oral anticoagulant
+
antiplatelet
Dual Antiplatelet
Therapy (DAPT)
Aspirin
+
P2Y12 inhibitor
(e.g., clopidogrel)
Triple Therapy (TT)
Warfarin
+
Aspirin
+
Clopidogrel
Terminology

48. • A 62-year-old man presents to his primary care physician with a 4-month history of pain in his lower legs. He
reports experiencing pain after he walks for a sustained period of time but is concerned that the distance.
he is able to walk has decreased over time. He now feels the pain even when walking around a shopping
mall. The pain resolves completely with rest. His medical history includes hyperlipidemia, hypertension, and
diabetes. Medications include atorvastatin, lisinopril, and metformin. Allergies include penicillin and
aspirin. He previously took another drug but discontinued it because he developed thrombotic
thrombocytopenic purpura. His blood pressure is 131/82 mmHg, pulse is 77/min, and respirations are
14/min.
• Which drug will be prescribed to this patient?
• What is the mechanism of the drug that should be given to this patient?
a) Adenosine diphosphate receptor antagonist
b) Glycoprotein IIb/IIIa receptor antagonist
c) Irreversible inhibitor of cyclooxygenase
d) Phosphodiesterase III inhibitor
e) Vitamin K epoxide reductase inhibitor
Lower extremity pain on exertion, relieved by rest - vascular claudication and has had negative reactions to
aspirin and ticlopidine. He should therefore be given a phosphodiesterase inhibitor such as cilostazol.

49. Lower extremity pain on exertion, relieved by rest - vascular claudication and has had negative reactions to aspirin and
ticlopidine. He should therefore be given a phosphodiesterase inhibitor such as cilostazol.
Incorrect Answers:
Answer 1: Adenosine diphosphate receptor antagonists such as clopidogrel and ticlopidine are also indicated for the
treatment of claudication; however, they have a side effect of thrombotic thrombocytopenic purpura that this patient
experienced leading to treatment discontinuation.
Answer 2: Glycoprotein IIb/IIIa receptor antagonists such as abciximab prevent platelet aggregation and are commonly used
in acute coronary syndromes or after coronary angioplasty; however, they are not as commonly used to treat claudication.
Answer 3: Irreversible inhibitor of cyclooxygenase describes the mechanism of action for aspirin, which could definitely be
used to treat claudication; however, this patient is allergic to aspirin.
Answer 5: Vitamin K epoxide reductase inhibitor describes the mechanism of action for warfarin, which is an anticoagulant
that can be used to prevent clot formation. This drug would not be used for claudication.

50. • A 3-year-old boy is brought to the emergency department by his mother after he is found unresponsive in
his crib. The mother reports that the patient has had several days of sore throat, loss of appetite, and fever,
which had been getting better. This morning, the patient had an episode of vomiting despite not eating
much and has been lethargic for several hours. Earlier, the patient had been complaining of a headache,
before being found unresponsive but breathing in his room. On exam, the patient's temperature is 98.8°F
(37.1°C), blood pressure is 108/76 mmHg, pulse is 90/min, and respirations are 14/min. The patient
withdraws to pain but otherwise does not respond. There is a faint rash on his palms. There is no neck
stiffness, and Kernig and Brudzinski signs are negative. The mother reports that she had attempted treating
the patient at home. Which of the following is the mechanism of the likely agent?
a) Irreversible cyclooxygenase inhibitor
b) Lipoxygenase inhibitor
c) Reversible cyclooxygenase inhibitor
d) Selective cyclooxygenase inhibitor
e) Thromboxane synthase inhibitor
a)
A child initially with cold-like symptoms with improvement, but then subsequent rash, vomiting, lethargy, and
altered mental status, no evidence of meningismus, and recent medication intake most likely has Reye syndrome
due to aspirin administration, an irreversible nonselective cyclooxygenase inhibitor.