How Does Clopidogrel (Anti-platelets) Work? (+ Pharmacology)

Summary

This video provides a detailed explanation of anti-platelet medications, particularly ADP P2Y12 receptor antagonists like clopidogrel. The video covers platelet function, how these drugs work to prevent blood clot formation, and the mechanisms behind platelet aggregation and inhibition. It breaks down various anti-platelet drugs into thionyl-pyridines and non-thionyl-pyridines, explaining their different properties, indications, dosages, and side effects. Key drugs discussed include clopidogrel, prasugrel, ticagrelor, and cangrelor. The video emphasizes the importance of using these medications for patients at high risk of thrombus-related complications, such as heart attacks, strokes, and pulmonary embolism.

Takeaways

• 😀 Platelets circulate in the bloodstream as 'calm' platelets until they detect damage, at which point they become activated and aggregate to form a platelet plug.
• 😀 ADP and thromboxane A2 are key signals that drive platelet aggregation, and drugs like clopidogrel block ADP receptors to prevent blood clot formation.
• 😀 ADP receptor antagonists, including clopidogrel, prasugrel, and ticagrelor, are crucial in preventing thrombus formation, which can lead to strokes, heart attacks, and pulmonary embolisms.
• 😀 A thrombus is an unwanted blood clot that, if dislodged, can travel and block blood flow in vital organs like the brain, heart, or lungs, causing serious health complications.
• 😀 Antiplatelet medications are primarily used for patients who have had a stroke, heart attack, or who are at high risk for these conditions, such as those undergoing chemotherapy.
• 😀 The ADP receptor antagonists can be classified into two groups: thionylpyridines (like clopidogrel) and non-thionylpyridines (like ticagrelor), with differences in their mechanisms and side effects.
• 😀 Thionylpyridines contain a sulfur group, making them irreversible inhibitors, while non-thionylpyridines are reversible inhibitors, leading to faster onset of action.
• 😀 Clopidogrel (Plavix) is a prodrug that requires activation via CYP2C19 enzymes, so drug interactions affecting this enzyme must be considered.
• 😀 Prasugrel (Effient) is the most potent ADP receptor antagonist but should be used cautiously in patients weighing less than 60 kg and only in those who have undergone coronary artery stent placement.
• 😀 Ticagrelor (Brilinta) should not be used with aspirin doses greater than 100 mg daily, as this can antagonize its effects. It is often used in patients with or without stents.
• 😀 Common side effects of ADP receptor antagonists include bleeding, bruising, and dyspepsia, with severe bleeding risks such as hemorrhage in the brain being a concern.
• 😀 IV ADP receptor antagonists, such as cangrelor (Kengreal), have the fastest onset of action and are used specifically during surgery.

Q & A

What is the primary function of platelets in the blood?

Platelets play a crucial role in blood clotting by aggregating at the site of vascular injury to form a platelet plug. They are activated by thromboxane A2 and ADP, which signal platelets to bind together.

How do ADP P2Y12 receptor antagonists, like clopidogrel, work?

ADP P2Y12 receptor antagonists work by blocking the ADP receptor on platelets, preventing platelet aggregation and reducing the risk of clot formation. This helps in preventing blood clots that could lead to conditions like heart attacks and strokes.

What are the differences between thionyl and non-thionyl pyridines in ADP P2Y12 receptor antagonists?

Thionyl pyridines contain a sulfur group and act as irreversible inhibitors, while non-thionyl pyridines do not contain sulfur and are reversible inhibitors. This leads to a faster onset of action for non-thionyl pyridines.

What is the main side effect of ADP receptor antagonists?

The most common side effect of ADP receptor antagonists is bleeding, which can range from minor bruising to more severe hemorrhages, including brain hemorrhages. Other side effects include dyspepsia (stomach discomfort) and rashes, particularly with thionyl pyridines.

Why is clopidogrel considered a prodrug?

Clopidogrel is considered a prodrug because it needs to be metabolized by the liver, specifically by the enzyme CYP2C19, to become its active form. This means that the drug's effectiveness depends on the patient’s ability to activate it through this enzyme.

What is the role of ADP in platelet aggregation?

ADP binds to the P2Y12 receptor on platelets, leading to platelet activation and aggregation. This process forms a platelet plug that contributes to the formation of a blood clot.

Which ADP receptor antagonist is used intravenously during surgeries?

Cangrelor (brand name Kengreal) is the ADP receptor antagonist used intravenously during surgeries. It has the fastest onset of action and is used specifically in surgical settings.

What is the relationship between aspirin dosage and ticagrelor (Brilinta)?

The dosage of aspirin must not exceed 100 mg per day when used with ticagrelor, as higher doses of aspirin can antagonize the effect of ticagrelor and reduce its effectiveness.

When is prasugrel (Effient) typically used in patients?

Prasugrel is typically used in patients who have undergone percutaneous coronary intervention (PCI), which involves the placement of a stent in the coronary arteries. It is the most potent ADP receptor antagonist but should be avoided in patients weighing less than 60 kg due to the increased risk of bleeding.

What is the difference in how thionyl and non-thionyl pyridines are administered?

Thionyl pyridines (e.g., clopidogrel, prasugrel) are typically taken orally, while non-thionyl pyridines like cangrelor are administered intravenously, with ticagrelor being available both orally and intravenously depending on the clinical scenario.