EpistemisTicagrelor / Prasugrel
New Generation Antiaggregants (e.g. *Brilique*, *Efient*).
Mechanism
Mechanism of Action
Ticagrelor and Prasugrel are antiplatelet agents designed to overcome the activation limitations and interindividual variability of clopidogrel.
Prasugrel (Thienopyridine 3rd gen.)
It is a prodrug that requires a simplified and highly efficient single-step hepatic metabolic activation:
- Initial hydrolysis to plasma thiolactone by intestinal esterases.
- Subsequent rapid hepatic oxidation by CYP3A4 and CYP2B6 to generate the active metabolite.
- Irreversible and potent inhibition of the P2Y12 receptor.
- It does not present the genetic variability linked to CYP2C19.
Ticagrelor (Cyclopentyltriazolopyrimidine)
It is an active ingredient with a different chemical structure, being the first direct-acting P2Y12 antagonist:
- Reversible and direct allosteric binding inhibitor; It does not compete directly for the natural ADP binding site but rather alters the receptor conformationally.
- Does not require hepatic metabolic activation.
- Faster start and finish effect.
- The recovery of baseline hemostatic platelet count after discontinuing ticagrelor is progressive in only 3 to 5 days.
Pharmacokinetics
Pharmacokinetics
- Prasugrel: Rapid absorption, the active metabolite reaches maximum concentration in 30 minutes. High bioavailability. Half-life of the active metabolite about 7 hours; but platelet inhibition persists throughout the useful life of the platelet due to its irreversible binding.
- Ticagrelor: Rapid absorption with bioavailability of 36%. It is partially metabolized by CYP3A4 to a major active metabolite (AR-C124910XX) with similar potency on P2Y12. Elimination half-life of 7 to 9 hours, requiring administration of two daily doses.
Indicators and dose
Indications
- Prevention of atherothrombotic events in combination with ASA in adults with ACS undergoing PCI (Prasugrel only indicated if the coronary anatomy is known and PCI is planned).
- Prevention of highly complex stent thrombosis.
Dosage and Schemes
- Prasugrel: Single loading dose of 60 mg orally; followed by 10 mg once daily. For patients weighing < 60 kg or age 75 years, reduce maintenance to 5 mg once daily.
- Ticagrelor: Single loading dose of 180 mg orally; followed by a maintenance dose of 90 mg twice daily orally.
Pregnancy and Breastfeeding
FDA Category C. Contraindicated in pregnancy due to the lack of controlled safety studies and potential massive intrauterine hemorrhagic effects.
Security
Contraindications
| Drug | Absolute Contraindications | Specific Clinical Warnings |
|---|---|---|
| Prasugrel | Pathological active bleeding; personal history of ischemic stroke, transient ischemic attack (TIA) or previous intracranial hemorrhage (associated with a high and unacceptable risk of inducing massive recurrent intracranial hemorrhage); severe hepatic insufficiency. | Not routinely recommended in patients aged 75 years or body weight < 60 kg (if its use is necessary, use a reduced maintenance dose of 5 mg). |
| Ticagrelor | Active pathological bleeding; history of intracranial hemorrhage; moderate to severe liver failure; coadministration with strong CYP3A4 inhibitors. | Risk of inducing transient dyspnea (due to an increase in circulating extracellular plasma adenosine due to blockage of cellular uptake) and ventricular pauses or mild bradycardia in the initial phase of treatment. Moderate elevation of serum serum uric acid. |
Adverse Effects (ADR)
- Bleeding: Higher rate of major bleeding not associated with coronary artery bypass surgery compared to clopidogrel.
- Dyspnea (Ticagrelor): It affects up to 14% of patients treated with ticagrelor. Mild to moderate character, typically self-limited in the first weeks without requiring suspension of therapy.
- Increase in Creatinine (Ticagrelor): Mild and reversible increase due to possible alteration of renal hemodynamics mediated by adenosine.
Interactions
Ticagrelor is a weak inhibitor of CYP3A4 and a major substrate of this enzyme. CYP3A4 inducers drastically decrease its effectiveness. Concomitant use with high doses of ASA (> 100 mg per day) reduces the net antiplatelet efficacy of ticagrelor due to mechanisms that have not been fully elucidated, so it should be prescribed exclusively with low maintenance doses of ASA (75 - 100 mg).
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Hematology
- Cluster
- Antiplatelet Agents