Table of Contents
Introduction
Ticagrelor is an oral antiplatelet agent used in the management of acute coronary syndrome (ACS) and for secondary prevention of thrombotic events. It directly and reversibly inhibits the P2Y₁₂ receptor on platelets, thereby preventing ADP-induced platelet aggregation. Unlike thienopyridines like clopidogrel, it does not require metabolic activation, leading to a faster and more predictable onset of action.
Step-by-Step Mechanism of Action
- Direct, Reversible P2Y₁₂ Antagonism
Ticagrelor binds to the P2Y₁₂ ADP receptor on platelets in a non-competitive, reversible manner. - Inhibition of Platelet Aggregation
By blocking ADP signaling, it prevents activation of the GPIIb/IIIa receptor complex, which is crucial for platelet aggregation. - Active Metabolite Contribution
The active metabolite AR-C124910XX contributes similarly to the parent drug in inhibiting platelet function. - Adenosine Uptake Inhibition
Ticagrelor inhibits ENT1, a nucleoside transporter, increasing local adenosine levels. This results in vasodilation and may contribute to some of its side effects, like dyspnea.
Pharmacokinetic Parameters
| Parameter | Value |
|---|---|
| Bioavailability | ~36% (oral) |
| Protein Binding | >99% |
| Metabolism | Hepatic (CYP3A4) |
| Half-Life (Parent Drug) | ~7 hours |
| Half-Life (Metabolite) | ~8.5 hours |
| Excretion | Primarily biliary (fecal route) |
Clinical Uses
- Acute coronary syndrome (unstable angina, STEMI, NSTEMI)
- Secondary prevention of myocardial infarction
- Used with low-dose aspirin following PCI or stent placement
Adverse Effects
- Increased risk of bleeding (including gastrointestinal and intracranial)
- Dyspnea (commonly mild and transient)
- Bradyarrhythmias (rare)
- Headache, dizziness
- Elevated uric acid levels
- Nausea or abdominal discomfort
Comparative Analysis
| Feature | Ticagrelor | Clopidogrel |
|---|---|---|
| Activation | Direct-acting | Prodrug (requires activation) |
| Reversibility | Reversible | Irreversible |
| Onset of Action | Fast (~30–60 minutes) | Slower (~2–4 hours) |
| Platelet Recovery Time | 3–5 days | 7–10 days |
| Influence of CYP2C19 | None | High (genetic polymorphism risk) |
| Dosing | Twice daily | Once daily |
MCQs
1. Ticagrelor blocks which receptor on platelets?
A. GPIIb/IIIa
B. P2Y₁₂
C. PAR-1
D. GPVI
Answer: B
2. The binding of ticagrelor to its target is:
A. Irreversible
B. Non-competitive and irreversible
C. Reversible
D. Allosteric and permanent
Answer: C
3. Does ticagrelor require metabolic activation to be effective?
A. Yes
B. No
Answer: B
4. The enzyme responsible for ticagrelor metabolism is:
A. CYP2C19
B. CYP2D6
C. CYP3A4
D. CYP1A2
Answer: C
5. Which of the following is a common adverse effect of ticagrelor?
A. Constipation
B. Dyspnea
C. Hyperglycemia
D. Visual disturbances
Answer: B
6. Ticagrelor increases adenosine levels by inhibiting:
A. PDE3
B. ENT1
C. MAO
D. ADA
Answer: B
7. Compared to clopidogrel, ticagrelor has a:
A. Slower onset of action
B. Faster onset of action
C. Similar activation time
D. Longer latency period
Answer: B
8. After stopping ticagrelor, platelet function typically recovers in:
A. 1 day
B. 3–5 days
C. 7–10 days
D. >10 days
Answer: B
9. Standard dosing schedule for ticagrelor is:
A. Once weekly
B. Once daily
C. Twice daily
D. Every 6 hours
Answer: C
10. Which feature contributes to ticagrelor’s clinical advantage over clopidogrel?
A. Irreversible inhibition
B. Short half-life
C. No genetic variability in metabolism
D. IV administration
Answer: C
FAQs
1. Is ticagrelor a prodrug?
No, it is active in its administered form.
2. Can ticagrelor be used alone without aspirin?
It is typically used alongside low-dose aspirin for dual antiplatelet therapy.
3. Why does ticagrelor cause shortness of breath?
It raises adenosine levels, which can trigger a sensation of breathlessness in some patients.
4. Is ticagrelor safe in patients with CYP2C19 mutations?
Yes, its efficacy is not affected by CYP2C19 polymorphisms.
5. How long before surgery should ticagrelor be stopped?
Generally, it should be discontinued 5 days before elective surgery.
References
- DrugBank – Ticagrelor Pharmacology & Mechanism
- NCBI – Clinical Effects and Safety of Ticagrelor
- FDA Prescribing Information – Ticagrelor
- Goodman & Gilman’s: The Pharmacological Basis of Therapeutics
- Medscape – Ticagrelor Drug Summary
Related Links
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