Adenosine Diphosphate Receptor Inhibitors

Antiplatelets​​​​​​​

Antiplatelet ADP inhibitors have the same use as salicylics. These medications are prescribed to inhibit platelet aggregation, which in turn reduces clients’ risk for myocardial infarction, ischemic cerebrovascular accident, and angina. They are also prescribed to prevent reocclusion or restenosis of stents placed in the coronary arteries to enlarge lumens and enhance coronary blood flow.

Prototype and Other Medications

Classification: Antiplatelet Agents

The prototype ADP inhibitor medication is clopidogrel. Another medication in this category is ticlopidine​​​​​​​.

Expected Pharmacologic Action

Adenosine diphosphate receptor, or ADP, inhibitors block the ADP receptors on platelets. Blocking these receptors inhibits platelet aggregation. This action is irreversible and lasts the lifetime of the platelet. Therefore, the antiplatelet effects of these medications last 7 to 10 days.

Adverse Drug Reactions

Side effects of the ADP inhibitor antiplatelet medications include gastric upset, abdominal pain, diarrhea, and nausea, as well as a small risk, less than the risk posed by aspirin, for gastric ulceration or bleeding. While thrombotic thrombocytopenic purpura (TTP) is a rare adverse effect, always consider it when clopidogrel is prescribed. TTP causes platelets to form blood clots in small blood vessels, which can impair the blood supply to major organs. This process can deplete the supply of platelets, causing bleeding to occur.

Interventions

With ADP inhibitor antiplatelet medications, monitor for manifestations of gastrointestinal bleeding such as black, tarry, or dark-colored stools, abdominal pain, nausea, and hematemesis, which is bloody vomit. Also, monitor for warning manifestations of hemorrhagic cerebrovascular accidents and findings of bleeding, such as easy bruising, petechiae, and excessive bleeding from minor injuries. Because TTP is a potential complication, monitor for ecchymosis, which is bruising, or petechial rash, which is pinpoint hemorrhages just under the skin. Check platelet counts periodically for an early indication of TTP. 

Safety Alert

TTP is a rare adverse effect of ADP inhibitor antiplatelet medications. It causes intravascular hemolysis, or destruction of blood cells, and thrombosis, or blood clot formation in the blood vessels. Both of these events can impair the blood supply to major organs and deplete the body’s store of platelets causing bleeding to occur. Blood clots most commonly affect the kidneys and brain, causing related dysfunction of these organs. Fever and spontaneous bleeding from the gums and nose may also occur. It is important to observe for early manifestations of TTP so corrective action can be taken before affected organs experience permanent damage. Treatment involves immediate discontinuation of the medication and plasmapheresis for severe cases.

Administration

Give ADP inhibitor antiplatelet medications orally, once daily, either with or without food. Check platelet counts periodically during therapy. Due to the risk of hemorrhage, discontinue the medication 5 to 7 days before elective surgery. 

Client Instructions

While the medication can be taken without regard to food consumption, instruct clients to take ADP inhibitor antiplatelet medication with food to minimize gastrointestinal effects. If a client does experience diarrhea, advise the client to drink plenty of clear fluids. Avoid medications that can cause gastric distress and alcohol because of the risk of gastrointestinal irritation and bleeding. Instruct clients to report persistent gastric irritation, manifestations of unusual or prolonged bleeding, such as easy bruising, bleeding gums, and pinpoint purplish petechial rash, as well as manifestations of active bleeding. Instruct the client to seek immediate care for indications of a hemorrhagic stroke, such as sudden severe headache, unilateral weakness, numbness, paralysis, vision changes, nausea and vomiting, and seizures.

Contraindications and Precautions

Due to the potential for gastric irritation and bleeding, do not give clopidogrel to clients with peptic ulcer disease, bleeding disorders, thrombocytopenia, and intracranial bleeding. Use clopidogrel with caution in clients who take other medications that cause gastrointestinal irritation or those who have gastrointestinal bleeding, liver or kidney dysfunction, or a high risk for bleeding. 

Interactions

Due to the increased risk of bleeding, do not give clopidogrel with other anticoagulants, NSAIDs, glucocorticoids, and alcohol. The herbal supplements ginger, ginkgo biloba, feverfew, and evening primrose oil also increase the risk of bleeding. Proton pump inhibitors, however, reduce the antiplatelet effects of clopidogrel.