| Routes of|
|Elimination half-life||12 hours (single dose)|
4–5 days (repeated dosing)
|Excretion||Kidney and fecal|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||263.78 g·mol−1|
|3D model (JSmol)|
Ticlopidine, sold under the brand name Ticlid, is a medication used to reduce the risk of thrombotic strokes.It 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.
It was patented in 1973 and approved for medical use in 1978.
Ticlopidine is indicated for the prevention of strokes and when combined with aspirin, for people with a new coronary stent to prevent closure.
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.However, ticlopidine’s serious side effects make it less useful than its cousin, clopidogrel. Current recommendations no longer recommend ticlopidine’s use.
The use of ticlopidine is contraindicated in anyone with:
Because of the increased risk of bleeding, patients taking ticlopidine should discontinue the medication 10–14 days before surgery.
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.
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.
Ticlopidine interacts with several classes of medications. It increases the antiplatelet effects of aspirin and other NSAIDs.Taking ticlopidine at the same time as antacids decreases the absorption of ticlopidine. Ticlopidine inhibits liver CYP2C19 and CYP2B6 and thus can affect blood levels of medications metabolized by these systems.
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.By interfering with platelet function, ticlopidine prevents clots from forming on the inside of blood vessels. Anti-platelet effects start within 2 days and reach their maximum by 6 days of therapy. Ticlopidine’s effects persist for 3 days after discontinuing ticlopidine although it may take 1–2 weeks for platelet function to return to normal, as the medication affects platelets irreversibly. Therefore, new platelets must be formed before platelet function normalizes.
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'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.
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.Castaigne was acquired by Sanofi in 1973. Starting in 1978 the drug was marketed in France under the brand name Ticlid for people at high risk for thrombotic events, who had just come out of heart surgery, were undergoing hemodialysis, had peripheral vascular disease, or who were otherwise at risk for strokes and ischemic heart disease.
Ticlopidine was brought to market in the US by Syntex, which got the drug approved in 1991.Syntex was acquired by the Roche group in 1994. The first generic ticlopidine hydrochloride was FDA approved in 1999. As of April 2015, Roche, Caraco, Sandoz, Par, Major, Apotex, and Teva had discontinued generic ticlopidine and no ticlopidine preparations were available in the US.
Soon after its release, studies regarding ticlopidine found it had the potential to be helpful for other diseases including peripheral vascular disease,diabetic retinopathy, and sickle cell 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.
Aspirin, also known as acetylsalicylic acid (ASA), is a medication used to reduce pain, fever, or inflammation. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.
A transient ischemic attack (TIA), commonly known as a mini-stroke, is a brief episode of neurological dysfunction caused by loss of blood flow (ischemia) in the brain, spinal cord, or retina, without tissue death (infarction). TIAs have the same underlying mechanism as ischemic strokes. Both are caused by a disruption in blood flow to the brain, or cerebral blood flow (CBF). The definition of TIA was classically based on duration of neurological symptoms. The current widely accepted definition is called "tissue-based" because it is based on imaging, not time. The American Heart Association and the American Stroke Association (AHA/ASA) now define TIA as a brief episode of neurological dysfunction with a vascular cause, with clinical symptoms typically lasting less than one hour, and without evidence of infarction on imaging.
An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where anticoagulants have little effect.
Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent. It is taken by mouth. Onset of effects is about two hours and lasts for five days.
Coronary thrombosis is defined as the formation of a blood clot inside a blood vessel of the heart. This blood clot may then restrict blood flow within the heart, leading to heart tissue damage, or a myocardial infarction, also known as a heart attack.
Dipyridamole is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time.
Prasugrel, sold under the brand name Effient in the US, Australia and India, and Efient in the EU) is a medication used to prevent formation of blood clots. It is a platelet inhibitor and an irreversible antagonist of P2Y12 ADP receptors and is of the thienopyridine drug class. It was developed by Daiichi Sankyo Co. and produced by Ube and marketed in the United States in cooperation with Eli Lilly and Company.
Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the insertion of a permanent wire-meshed tube that is either drug eluting (DES) or composed of bare metal (BMS). The stent delivery balloon from the angioplasty catheter is inflated with media to force contact between the struts of the stent and the vessel wall, thus widening the blood vessel diameter. After accessing the blood stream through the femoral or radial artery, the procedure uses coronary catheterization to visualise the blood vessels on X-ray imaging. After this, an interventional cardiologist can perform a coronary angioplasty, using a balloon catheter in which a deflated balloon is advanced into the obstructed artery and inflated to relieve the narrowing; certain devices such as stents can be deployed to keep the blood vessel open. Various other procedures can also be performed.
Tirofiban, sold under the brand name Aggrastat, is an antiplatelet medication. It belongs to a class of antiplatelets named glycoprotein IIb/IIIa inhibitors. Tirofiban is a small molecule inhibitor of the protein-protein interaction between fibrinogen and the platelet integrin receptor GP IIb/IIIa and is the first drug candidate whose origins can be traced to a pharmacophore-based virtual screening lead.
Eptifibatide, is an antiplatelet drug of the glycoprotein IIb/IIIa inhibitor class. Eptifibatide is a cyclic heptapeptide derived from a disintegrin protein found in the venom of the southeastern pygmy rattlesnake. It belongs to the class of the arginin-glycin-aspartat-mimetics and reversibly binds to platelets. Eptifibatide has a short half-life. The drug is the third inhibitor of GPIIb/IIIa that has found broad acceptance after the specific antibody abciximab and the non-peptide tirofiban entered the global market.
P2Y12 is a chemoreceptor for adenosine diphosphate (ADP) that belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors. This P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. The P2Y12 receptor is involved in platelet aggregation and is thus a biological target for the treatment of thromboembolisms and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.
A drug-eluting stent (DES) is a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots (thrombi), could otherwise block the stented artery, a process called restenosis. The stent is usually placed within the peripheral or coronary artery by an interventional cardiologist or interventional radiologist during an angioplasty procedure.
The history of invasive and interventional cardiology is complex, with multiple groups working independently on similar technologies. Invasive and interventional cardiology is currently closely associated with cardiologists, though the development and most of its early research and procedures were performed by diagnostic and interventional radiologists.
The Thrombolysis In Myocardial Infarction, or TIMI Study Group, is an Academic Research Organization (ARO) affiliated with Brigham and Women's Hospital and Harvard Medical School dedicated to advancing the knowledge and care of patients suffering from cardiovascular disease. The TIMI Study Group provides robust expertise in the key aspects of a clinical trial, including academic leadership, global trial management, biostatistics, clinical event adjudication, safety desk, medical hotline, and core laboratories. The group has its headquarters in Boston, Massachusetts.
A coronary stent is a tube-shaped device placed in the coronary arteries that supply blood to the heart, to keep the arteries open in the treatment of coronary heart disease. It is used in a procedure called percutaneous coronary intervention (PCI). Coronary stents are now used in more than 90% of PCI procedures. Stents reduce angina and have been shown to improve survivability and decrease adverse events in an acute myocardial infarction.
Vorapaxar is a thrombin receptor antagonist based on the natural product himbacine, discovered by Schering-Plough and developed by Merck & Co.
Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It acts as a platelet aggregation inhibitor by antagonising the P2Y12 receptor. The drug is produced by AstraZeneca.
Cangrelor, sold under the brand name Kengreal in the United States and Kengrexal in the European Union) is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P2Y12 inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation. Unlike clopidogrel (Plavix), which is a prodrug, cangrelor is an active drug not requiring metabolic conversion.
Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute coronary syndrome (ACS) or in preventive treatment for patients who are in risk of thromboembolism, myocardial infarction or a stroke. These drugs antagonize the P2Y12 platelet receptors and therefore prevent the binding of ADP to the P2Y12 receptor. This leads to a decrease in aggregation of platelets, prohibiting thrombus formation. The P2Y12 receptor is a surface bound protein found on blood platelets. They belong to G protein-coupled purinergic receptors (GPCR) and are chemoreceptors for ADP.
Management of acute coronary syndrome is targeted against the effects of reduced blood flow to the afflicted area of the heart muscle, usually because of a blood clot in one of the coronary arteries, the vessels that supply oxygenated blood to the myocardium. This is achieved with urgent hospitalization and medical therapy, including drugs that relieve chest pain and reduce the size of the infarct, and drugs that inhibit clot formation; for a subset of patients invasive measures are also employed. Basic principles of management are the same for all types of acute coronary syndrome. However, some important aspects of treatment depend on the presence or absence of elevation of the ST segment on the electrocardiogram, which classifies cases upon presentation to either ST segment elevation myocardial infarction (STEMI) or non-ST elevation acute coronary syndrome (NST-ACS); the latter includes unstable angina and non-ST elevation myocardial infarction (NSTEMI). Treatment is generally more aggressive for STEMI patients, and reperfusion therapy is more often reserved for them. Long-term therapy is necessary for prevention of recurrent events and complications.