Antiplatelet drugs

Antiplatelet drugs

Antiplatelet drugs are used to prevent arterial thromboembolism, particularly in patients at risk for MI, stroke, and arteriosclerosis (hardening of the arteries).

Aspirin, clopidogrel, dipyridamole, sulfinpyrazone, and ticlopidine are examples of oral antiplatelet drugs. Antiplatelet drugs administered I.V. include abciximab, eptifibatide, and tirofiban.

Pharmacokinetics

When taken orally, antiplatelet drugs are absorbed very quickly and reach peak concentration in 1 to 2 hours. Aspirin maintains its antiplatelet effect for about 10 days, or as long as platelets normally survive. The effects of clopidogrel last about 5 days. Sulfinpyrazone may require several days of administration before its antiplatelet effects occur.

After I.V. administration, antiplatelet drugs are quickly distributed throughout the body. They’re minimally metabolized and excreted unchanged in urine. The effects of these drugs occur within 15 to 20 minutes of administration and last about 6 to 8 hours.

Elderly patients and patients with renal failure may have decreased clearance of antiplatelet drugs, which would prolong the antiplatelet effect.

Pharmacodynamics

Antiplatelet drugs interfere with platelet activity in different drug-specific and dose-related ways.

• Low doses of aspirin inhibit clot formation by blocking the synthesis of prostaglandin, which in turn prevents formation of the platelet-aggregating substance thromboxane A₂.
• Clopidogrel inhibits platelet aggregation by inhibiting platelet-fibrinogen binding.
• I.V. antiplatelet drugs inhibit the glycoprotein IIa-IIIb receptor, which is the major receptor involved in platelet aggregation.
• Dipyridamole may inhibit platelet aggregation because it increases adenosine, a coronary vasodilator and platelet aggregation inhibitor.
• Ticlopidine inhibits the binding of fibrinogen to platelets during the first stage of the clotting cascade.
• Sulfinpyrazone inhibits several platelet functions. It lengthens platelet survival and prolongs the patency of arteriovenous shunts used for hemodialysis. A single dose rapidly inhibits platelet aggregation.

Pharmacotherapeutics

Antiplatelet drugs have many different uses.

Managing MIs

Aspirin is used in patients who have had a previous MI or who have unstable angina to reduce the risk of death in patients at high risk for CAD. It’s also prescribed to reduce the risk of transient ischemic attacks (TIAs) (temporary reduction in circulation to the brain).

Clopidogrel is used to reduce the risk of stroke or vascular death in patients with a history of a recent MI, stroke, or established peripheral artery disease. Clopidogrel is also used to help treat acute coronary syndromes, especially in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft.

Eptifibatide may be used for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention (PCI). Abciximab may also be used in combination with PCI. Tirofiban may be used to treat acute coronary syndrome.

Salve for surgery

Dipyridamole is used with a coumarin compound to prevent thrombus formation after cardiac valve replacement. Dipyridamole may be administered with aspirin to prevent blood clots in patients who have had coronary artery bypass grafts (bypass surgery) or prosthetic (artificial) heart valves.

Warning!

Adverse reactions to antiplatelet drugs

Hypersensitivity reactions, particularly anaphylaxis, can occur. Bleeding is the most common adverse reaction when I.V. antiplatelet drugs are administered.

Aspirin

• Stomach pain
• Heartburn, nausea
• Constipation
• Blood in stool
• Slight gastric blood loss

Clopidogrel

• Headache
• Skin ulceration
• Joint pain
• Flulike symptoms
• Upper respiratory tract infection

Sulfinpyrazone

• Abdominal discomfort

Ticlopidine

• Diarrhea
• Nausea
• Dyspepsia
• Rash
• Elevated liver function test results
• Neutropenia

Dipyridamole

• Headache
• Dizziness
• Nausea
• Flushing
• Weakness
• Fainting
• Mild GI distress

Circumventing stroke

Ticlopidine is used to reduce the risk of thrombotic stroke in high-risk patients, such as those with a history of frequent TIAs or a previous thrombotic stroke.

Drug interactions

• Antiplatelet medications taken with NSAIDs, heparin, oral anticoagulants, or another antiplatelet medication increase the risk of bleeding.
• Sulfinpyrazone taken with aspirin and oral anticoagulants increases the risk of bleeding.

Tales of toxicity

• Aspirin increases the risk of toxicity of methotrexate and valproic acid.
• Aspirin and ticlopidine may reduce the effectiveness of sulfinpyrazone to relieve signs and symptoms of gout.
• Antacids may reduce the plasma levels of ticlopidine.
• Cimetidine increases the risk of ticlopidine toxicity and bleeding.

You just don’t know

Because guidelines haven’t been established for administrating ticlopidine with heparin, oral anticoagulants, aspirin, or fibrinolytic drugs, these drugs should be discontinued before ticlopidine therapy begins.