Clopidogrel: Mechanism and Indications

Overview

• Clopidogrel is an oral antiplatelet medication used to prevent blood clots in patients with acute coronary syndromes, recent myocardial infarction, or stroke.
• It belongs to the thienopyridine class of platelet inhibitors.

Mechanism of Action

• Inhibits the P2Y12 receptor on platelet surfaces, preventing platelet activation and aggregation.
• Activated by liver enzymes, specifically CYP2C19, to form an active metabolite.

Indications

• Acute coronary syndrome (ACS)
  • Unstable angina
  • Non-ST-segment elevation myocardial infarction (NSTEMI)
  • ST-segment elevation myocardial infarction (STEMI)
• Recent myocardial infarction
• Stroke
• Peripheral artery disease

Pharmacokinetics

• Rapid absorption after oral administration
• Peak plasma concentration reached within 2 hours
• Elimination half-life: 6-8 hours
• Metabolized by liver enzymes, primarily CYP2C19

Adverse Effects

• Bleeding (most common)
• Gastrointestinal upset (diarrhea, nausea, vomiting)
• Rash
• Headache
• Dizziness

Contraindications

• Active bleeding
• Allergy to clopidogrel
• Severe liver disease
• Pregnancy and breastfeeding (category B)

Interactions

• NSAIDs (increased risk of bleeding)
• Warfarin (increased risk of bleeding)
• CYP2C19 inhibitors (e.g., omeprazole, fluoxetine)
• CYP2C19 inducers (e.g., rifampin)

Dosing and Administration

• Standard dose: 75 mg once daily
• Loading dose: 300-600 mg (optional)
• Dose adjustments may be necessary for patients with severe liver disease or CYP2C19 poor metabolizers

Overview of Clopidogrel

• Oral antiplatelet medication used to prevent blood clots in patients with acute coronary syndromes, recent myocardial infarction, or stroke.
• Belongs to the thienopyridine class of platelet inhibitors.

Mechanism of Action

• Inhibits the P2Y12 receptor on platelet surfaces, preventing platelet activation and aggregation.
• Activated by liver enzymes, specifically CYP2C19, to form an active metabolite.

Indications for Use

• Acute coronary syndrome (ACS), including unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
• Recent myocardial infarction.
• Stroke.
• Peripheral artery disease.

Pharmacokinetics

• Rapid absorption after oral administration.
• Peak plasma concentration reached within 2 hours.
• Elimination half-life: 6-8 hours.
• Metabolized by liver enzymes, primarily CYP2C19.

Adverse Effects

• Bleeding (most common adverse effect).
• Gastrointestinal upset, including diarrhea, nausea, and vomiting.
• Rash.
• Headache.
• Dizziness.

Contraindications

• Active bleeding.
• Allergy to clopidogrel.
• Severe liver disease.
• Pregnancy and breastfeeding (category B).

Interactions

• NSAIDs increase the risk of bleeding.
• Warfarin increases the risk of bleeding.
• CYP2C19 inhibitors (e.g., omeprazole, fluoxetine) decrease the effectiveness of clopidogrel.
• CYP2C19 inducers (e.g., rifampin) increase the effectiveness of clopidogrel.

Dosing and Administration

• Standard dose: 75 mg once daily.
• Loading dose: 300-600 mg (optional).
• Dose adjustments may be necessary for patients with severe liver disease or CYP2C19 poor metabolizers.