Antiplatelet agents ticlopidine

Anticoagulant (warfarin) and antiplatelet agents (ticlopidine, clopidogrel) reduced platelet adhesiveness and G1 tract damage by NSAIDs increase risk of alimentary bleeding (notably with azapropazone). Phenylbutazone, and probably azapropazone, inhibit the metabolism of warfarin, increasing its effect. 

The widely used platelet inhibitor aspirin or acetylsalicylic acid, by acetylating the enzyme cyclooxygenase, inhibits platelet function by preventing the formation of thromboxane A2 and the synthesis of prostaglandin I2 (PGI2) (68). Aspirin has been used in combination with other antiplatelet agents such as ticlopidine, which inhibits ADP-induced platelet aggregation (69). 

White C, Chaitman B, Knudtson M, Chisholm R. Antiplatelet agents are effective in reducing the acute ischemic complications of angioplasty but do not prevent restenosis results from the ticlopidine trial. Coron Artery Dis 1991 2 757-767. 

Sekiguchi M, Hoshizaki H, Adachi H, Ohshima S, Taniguchi K, Kurabayashi M, Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting A randomized comparison of ticlopidine and cilostazol. Circ J 2004 68(7) 6I0-6I4,... 

Currently, the two antiplatelet agents with proven efficacy are aspirin, which inhibits cyclooxygenase -dependent synthesis of thromboxane Aj (TXj ), and ticlopidine, wdrich blocks the ability of ADP to inhibit stimulated adenyl cyclase. Bodi of these drags have proven prophylactic uses in reducing the risk of thrombo -occlusive and thromboembolic complications for all major arterial beds in individuals with a previous history of such episodes. Controlled trials show that both aspirin and ticlopidine are indicated in the secondary prevention of stroke, myocardial induction and peripheral vascular occlusion. However, there are limitations to their efficacy. No net changes in vascular events are seen with primary prevention. Moreover, antiplatelet drugs do not alter thrombocytopenia or impairment... 

White CW, Chaitman B, Lassar TA, Marcus ML, Chisholm RJ, Knudson M, Morton B, Roy L, Khaja F Antiplatelet agents are effective in reducing the immediate complications of PTCA Results from the ticlopidine multicenter trial. Circulation 2 400,1987... 

Antiplatelet therapy plays a key role in the treatment of ACS, such as Ml. Aspirin has been shown to decrease overall mortality and reinfarction and is recommended for all patients in this setting unless contraindicated. Aspirin should be given at the lowest effective dose, to ensure efficacy and to limit adverse reactions. If aspirin is contraindicated or not tolerated, thienopyridines (clopidogrel or ticlopidine) may be used. Comparisons of oral antiplatelet agents are summarized in Thumbnail. 

The efficacy of clopidogrel as an antiplatelet agent in atherothrombotic disorders was demonstrated in the CAPRIE trial. In this study of more than 19,000 patients with a history of either myocardial infarction (MI), stroke, or peripheral arterial disease (PAD), clopidogrel 75 mg/day was compared with aspirin 325 mg/day for its ability to decrease MI, stroke, or cardiovascular death. In the final analysis, clopidogrel was slightly (8% relative risk reduction [RRR]) more effective than aspirin (p =. 043) and had a similar incidence of adverse effects. It is not associated with the blood dyscrasias (neutropenia) common with its congener, ticlopidine, and is used widely in patients with atherosclerosis. 

Ticlopidine is a thienopyridine antiplatelet agent, similar in structure and mechanism of action to clopidogrel. It has been shown to reduce the risk of stroke by 30% compared with placebo and by 21% compared with aspirin 325 mg/day inpatients at risk. The use of ticlopidine has been severely restricted by its side-effect profile, however. It causes bone marrow suppression, rash, diarrhea, and elevation of the serum cholesterol concentration. Neutropenia occurs in up to 2% of patients and generally is reversible. More problematic, however, is the increased risk of aplastic anemia and thrombotic thrombocytopenic purpura. Ticlopidine 250 mg twice daily is stiU available as an alternative in patients who fail or are intolerant of other therapies but is rarely needed. 

There are no documented drug interactions, but garlic s antiplatelet effect might be dangerous in patients taking warfarin or antiplatelet agents such as aspirin, clopidogrel, ticlopidine, or dipyridamole. 

Ticlopidine, a platelet aggregation inhibitor possessing antithrombotic effects (250 mg p.o. b.i.d.), is used to reduce the risk of thrombotic stroke in patients with a history of stroke or who have experienced stroke precursors (see also Figures 13 and 93). Ticlopidine, a thienopyridine derivative, and a new antiplatelet agent for secondary prevention of stroke, causes potent inhibition of adenosine diphosphate (ADP)-induced platelet aggregation and moderate inhibition... 

The main quantitative metabolic route in man is N.dealkylation, followed by oxidation with opening of the thiophene ring (17) but another metabolic pathway is responsible for the 2-keto derivative of ticlopidine called PCR-3787. This metabolite, which has been found in small concentrations in rat bile, has been found to be 5 to 10 times more potent than ticlopidine itself as an antiplatelet agent, although its potential contribution to ticlopidine s effect is as yet uncertain (24). 

Ginseng ASA, NSAIDs Antidiabetic agents Clopidogrel, ticlopidine CNS stimulants, caffeine Corticosteroids Digoxin MAO inhibitors Warfarin Additive antiplatelet effects Additive hypoglycemia Additive antiplatelet effects Additive CNS toxicity Additive CNS toxicity Falsely elevated levels Increased toxicity Increased risk of bleeding... 

Ticlopidine (Fig. 5.11) is a substituted thiophene that has been used clinically as an antiplatelet aggregation agent and has been identified as a mechanism-based inactivator of CYP2C19... 

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