Pharmacology of ADP Receptor Inhibitors

ADP receptor inhibitors are a class of antiplatelet drugs used to treat a variety of cardiovascular thrombotic events. Here, we review its members, their mechanism of action, and their side effect and drug interaction profiles.

Examples of ADP receptor inhibitors include:

  • Clopidogrel
  • Prasugrel
  • Ticagrelor

ADP receptor inhibitors are used to treat the following indications:

  • Acute coronary syndrome (ACS) – where they are used to initiate rapid antiplatelet effect.
  • Coronary artery stents – where ADP inhibitors are used to prevent blockage.
  • Cardiovascular prophylaxis – secondary prevention of thrombotic events in high-risk patients.

The purpose of ADP receptor inhibitors is, then, to prevent development of thrombi and to initiate antiplatelet therapy where thrombi have already formed.

Mechanism of action

There are two classes of ADP receptor inhibitor:

  • Thienopyridines – clopidogrel, prasugrel
  • Newer generation agents – ticagrelor

This classification matters.

Thienopyridines irreversibly inhibit the ADP receptor, whereas ticagrelor reversibly binds to the receptor. This binding bears significance because all thienopyridines are prodrugs which need to be converted to the active ingredient in vivo.

The same is not true of ticagrelor. As a result, ticagrelor displays faster onset / offset of action.

ADP receptor inhibitors bind to the P2Y12 subtype of the ADP (adenosine diphosphate) receptor.

This receptor is found on the surface of platelets. By binding to the receptor, ADP inhibitors prevent platelet aggregation and cross-linking by the protein fibrin, reducing risk of arterial blockage.

Side effects

Side effects with ADP receptor inhibitors include:

  • Increased risk of bleeding
  • Easy bruising
  • Heartburn
  • Itch
  • Headache
  • Abdominal pain
  • Diarrhea

In rare cases, ADP receptor inhibitors are linked to thrombocytopenia.

Clinical considerations

When we consider the clinical aspects of ADP receptor inhibitors, we need to think about the following factors:

  • That ADP receptor inhibitors are avoided in cases of active bleeding. They may also be avoided in the days leading up to elective surgery.
  • That because many ADP receptor inhibitors are prodrugs, their antiplatelet effects are reduced by drugs that are CYP inhibitors – such as omeprazole, erythromycin, ciprofloxacin, some SSRIs and some antifungal drugs etc.
  • That taking ADP receptor inhibitors with other antiplatelet drugs increases the risk of bleeding – NSAIDs, aspirin, heparin etc.
  • That they are often used, particularly clopidogrel, along with aspirin, in the immediate aftermath of heart attacks and after a coronary stent has been implanted. A proton-pump inhibitor may also be used for gastroprotective purposes.

ADP receptor inhibitors remain an important class of antiplatelet drugs that serve to reduce mortality, both in patients with existing cardiovascular events and in those likely to experience such events in the future.

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