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Ticlopidine (trade name Ticlid ) is an antiplatelet drug in the thienopyridine family which is an adenosine diphosphate (ADP) receptor inhibitor. Research initially showed that it was useful for preventing strokes and coronary stent occlusions. However, because of its rare but serious side effects of neutropenia and thrombotic thrombocytopenic purpura it was primarily used in patients in whom aspirin was not tolerated, or in whom dual antiplatelet therapy was desirable. With the advent of newer and safer antiplatelet drugs such as clopidogrel and ticagrelor, its use remained limited.
2 Medical uses
2.2 Heart disease
4 Adverse effects
6 Pregnancy and lactation
7 Mechanism of action
9 Drug-drug interactions
10 Chemical properties
Ticlopidine was discovered in the 1970s in France by a team led by Fernand Eloy and including Jean-Pierre Maffrand at Castaigne SA that was trying to discover a new anti-inflammatory medication. Pharmacology developers noted that this new compound had strong anti-platelet properties.
Ticlopidine was brought to market in the US by Syntex, which got the drug approved in 1991.
This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. (June 2015)
Ticlopidine is FDA approved for the prevention of strokes and, when combined with aspirin, for patients with a new coronary stent to prevent closure. There are also several off-label uses, including acute treatment of myocardial infarction and unstable angina, peripheral vascular disease, prevention of myocardial infarctions, diabetic retinopathy, and sickle cell disease.
Ticlopidine is considered a second-line option for the prevention of thrombotic strokes among patients who have previously had a stroke or TIA. Studies have shown that it is superior to aspirin in the prevention of death or future strokes. However, it also has more frequent and serious side effects compared to aspirin, so it is reserved for those patients that cannot take aspirin.
When a patient needs to have a stent placed in one of the vessels around their heart, it is important that that stent stay open to keep blood flowing to the heart. Therefore, patients with stents must take medications after the procedure to help maintain that blood flow. Ticlopidine, taken together with aspirin, is FDA approved for this purpose, and in studies it has been shown to work better than aspirin alone or aspirin with an anticoagulant.
Soon after its release, studies regarding ticlopidine found it had the potential to be helpful for other diseases including peripheral vascular disease, However none had enough evidence for FDA approval. Due to the blood cell side effects associated with ticlopidine, researchers for treatments for these conditions have turned to other avenues.
The most serious side effects associated with ticlopidine are those that affect the blood cells, although these life-threatening complications are relatively rare. The most common side effects include:
Ticlopidine may also cause an increase in cholesterol, triglycerides, liver enzymes, and bleeding.
Use of ticlopidine has been associated with neutropenia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and aplastic anemia. Because of this risk, patients who are started on ticlopidine are typically monitored with blood tests to test their cell counts every two weeks for the first three months.
The use of ticlopidine is contraindicated in anyone with:
Increased risk of bleeding (i.e. frequent falls, gastrointestinal bleeds)
History of hematological disease
Severe liver disease
History of allergic reaction to ticlopidine or any thienopyridine drug such as clopidogrel
Because of the increased risk of bleeding, patients taking ticlopidine should discontinue the medication 10–14 days before surgery.
Pregnancy and lactation
Ticlopidine is a FDA pregnancy risk category B. There have been no studies done in humans. Studies in rats show that high drug levels could cause toxicity in both mother and fetus, but there are no known birth defects associated with its use.
There have been no studies to test whether ticlopidine goes into breast milk. Studies in rats have shown that it is passed in rats’ milk.
Mechanism of action
Ticlopidine is a thienopyridine which, when metabolized by the body, irreversibly blocks the P2Y12 component of the ADP receptor on the surface of platelets. Without ADP, fibrinogen does not bind to the platelet surface, preventing platelets from sticking to each other.
Ticlopidine is ingested orally with 80% bioavailability with rapid absorption. Even higher absorption can occur if ticlopidine is taken with food. It is metabolized by the liver with both renal and fecal elimination. Clearance is nonlinear and varies with repeated dosing. After the first dose the half life is 12.6 hours, but with repeated dosing the maximum half life is 4–5 days. Clearance is also slower in the elderly. The drug is 98% reversibly bound to proteins.
Ticlopidine interacts with several classes of medications. It increases the antiplatelet effects of aspirin and other NSAIDs. and thus can affect blood levels of medications metabolized by these systems.
Ticlopidine’s systemic name is 5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2- c ]pyridine. Its molecular weight is 263.786 g/mol. It is a white crystalline solid. It is soluble in water and methanol and somewhat soluble in methylene chloride, ethanol, and acetone. It self buffers in water to a pH of 3.6.
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