PRASU 5

Indications

• Prevention of atherothrombotic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Dosage

Adults: Adults aged 18 to 74 years with a body weight of less than 60 kg should receive an initial dose of 60 mg, followed by 5 mg once daily usually for up to 12 months. For those weighing 60 kg and above, the same initial dose applies, with the continued daily dose also being 5 mg.

Mechanism of action

Prasugrel is a prodrug that inhibits ADP receptors by irreversibly binding to the P2Y12 receptor on platelets. This prevents the binding of adenosine diphosphate (ADP) to its receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, which is crucial for platelet aggregation.

Pharmacodynamics

As a thienopyridine ADP receptor inhibitor, prasugrel effectively inhibits platelet aggregation by irreversibly binding to the P2Y12 receptors. This irreversible binding leads to a significant reduction in platelet activation, which is essential for preventing thrombus formation in acute coronary syndromes.

Pharmacokinetics

Prasugrel is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 30 to 60 minutes. The drug undergoes bioactivation in the liver to its active metabolite, which has a longer duration of action. The elimination half-life of prasugrel is approximately 7 hours, and it is primarily excreted via urine and feces. Factors such as liver and renal impairment may affect its pharmacokinetics, necessitating caution in these populations.

Contra-indications

• Active bleeding
• History of hypersensitivity to prasugrel or other thienopyridines
• Severe hepatic impairment

Adverse effects

• Anaemia
• Haemorrhage
• Angioedema
• Thrombocytopenia
• Skin rash

Interactions

• Aspirin (increased risk of bleeding)
• Other antiplatelet agents (increased risk of bleeding)
• Non-steroidal anti-inflammatory drugs (NSAIDs) (increased risk of gastrointestinal bleeding)

Precautions

• Caution in patients with body weight less than 60 kg
• Increased risk of bleeding in elderly patients or those with recent trauma, surgery, gastrointestinal bleeding, or active peptic ulcer disease
• Caution in patients with moderate renal or hepatic impairment

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises to avoid due to lack of information on excretion in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Prasugrel 5 mg tablets
• Prasugrel 10 mg tablets

Mechanism of action

Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel. The P2Y(12) receptor plays a crucial role in platelet aggregation and is the target of platelet aggregation inhibitors, including the thienopyridine compound prasugrel. The present study analyzed the effects of R-138727 (2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid), the active metabolite of prasugrel, on recombinant wild-type and mutant human P2Y(12) receptors in order to identify the molecular site of action of R-138727. The function of wild-type and mutant P2Y(12) receptors stably expressed in Chinese hamster ovary cells was assessed by measuring the 2-methylthio-ADP-mediated inhibition of forskolin-stimulated cellular cAMP production. RESULTS: In cells expressing wild-type receptors, R-138727 potently inhibited receptor function with a half-maximal concentration below 1 uM. The mode of action was irreversible. The same effect of R-138727 was observed in cells expressing Cys17Ala/Cys270Ala constructs. In contrast, in cells expressing either a Cys97Ala construct or a Cys175Ala construct, R-138727 failed to inhibit the response to the agonist. When cells expressing wild-type receptors were pretreated with the P2 receptor antagonists ATP or suramin, no effect of R-138727 was observed. Similar experiments with N-acetylcysteine 10 uM showed no interference of N-acetylcysteine with R-138727. The experiments demonstrate a potent and irreversible action of R-138727 at the recombinant human P2Y(12) receptor. The data suggest that R-138727 interacts with cysteine 97 (upper portion of the predicted third transmembrane region) and cysteine 175 (second extracellular loop) of the receptor, which are likely to form a disulfide bridge in native receptors. Moreover, the data also suggest that this site of action of R-138727 is close to the ligand-binding site of the receptor. /R-138727/ Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Pharmacodynamics

Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 receptors.