Disease relevance of TICLOPIDINE HYDROCHLORIDE

• After coronary stenting, aspirin and ticlopidine should be considered for the prevention of the serious complication of stent thrombosis [1].
• Ticlopidine and thrombotic thrombocytopenic purpura [2].
• Ticlopidine and thrombocytopenia [3].
• We assessed the effect of ticlopidine, an inhibitor of platelet aggregation, on the long-term patency of saphenous-vein bypass grafts for the treatment of peripheral vascular disease [4].
• With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted [5].

Psychiatry related information on TICLOPIDINE HYDROCHLORIDE

• The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates) [5].
• Individual patient-by-patient analysis shows that patency of all grafts at each study time, is more frequent in the ticlopidine group [6].

High impact information on TICLOPIDINE HYDROCHLORIDE

• Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice [7].
• Toxic erythroderma due to ticlopidine [8].
• CONCLUSIONS: Ticlopidine significantly improved the long-term patency of saphenous-vein bypass grafts in the legs [4].
• After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin) [9].
• Ticlopidine and TTP after coronary stenting [10].

Chemical compound and disease context of TICLOPIDINE HYDROCHLORIDE

• Randomized studies in patients undergoing coronary artery stenting have shown that ticlopidine reduces the risk for subacute stent thrombosis compared with warfarin-based regimens [11].
• Treatment of the patient with the antithyroid drug thiamazol and temporary corticosteroids, aspirin, and ticlopidine did not correct the platelet hypersensitivity to ristocetin [12].
• CONCLUSIONS: The combined use of ticlopidine, ASA and heparin effectively controls activation of coagulation in patients with stable or unstable angina undergoing coronary dilation [13].
• Phenytoin toxicity associated with ticlopidine administration [14].
• OBJECTIVES: This study sought to determine whether the duration of pretreatment with the adenosine diphosphate receptor antagonist ticlopidine prior to intracoronary stenting is associated with the incidence of procedure-related non-Q-wave myocardial infarctions (MIs) [15].

Biological context of TICLOPIDINE HYDROCHLORIDE

• To elucidate the bleeding tendency that follows the administration of ticlopidine, we investigated the skin bleeding time and some ex vivo functions of platelets obtained from eight healthy volunteers before and 1 wk after daily administration of 500 mg of ticlopidine [16].
• The onset of ticlopidine-associated thrombotic thrombocytopenic purpura is difficult to predict, despite close monitoring of platelet counts [17].
• BACKGROUND: This study was performed to analyze the influence of either aspirin, ticlopidine, or their combination on platelet activation and aggregation parameters after stent implantation [18].
• Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin [19].
• Significant reductions in systemic vascular resistance were observed in the ticlopidine group, in contrast to no significant decrease in the aspirin group [20].

Anatomical context of TICLOPIDINE HYDROCHLORIDE

• A stent-induced increase in platelet P-selectin (CD62P) expression and an increase in neutrophil Mac-1 (CD11b) expression were suppressed in the cilostazol group compared with the ticlopidine group [21].
• Clopidogrel, an analogue of ticlopidine, was developed because it did not show bone marrow toxic effects in either tissue culture or animal models [22].
• The erythrocyte aggregation rates at 4 and 8 weeks were significantly lower (P < .05 by Bonferroni's modified t test) than those before ticlopidine administration [23].
• Using human liver microsomes, we showed that ticlopidine is a potent inhibitor of cytochrome P450 2C19, with an estimated inhibition constant (Ki) of 3.7 +/- 0.2 mumol/L [24].
• AIMS: Vascular complications associated with femoral artery access for interventional cardiological procedures may increase morbidity especially in patients receiving anticoagulants, aspirin, ticlopidine and platelet glycoprotein IIb/IIIa receptor inhibitors [25].

Associations of TICLOPIDINE HYDROCHLORIDE with other chemical compounds

• Clopidogrel, an inhibitor of platelet aggregation, was initially thought to be free of the side-effects of ticlopidine [26].
• Ex vivo platelet aggregation in response to 20 mumol/L ADP and 4 micrograms/mL collagen was measured over time after the first dose of either xemilofiban (5, 10, 15, or 20 mg) or placebo (ticlopidine) administered 8 to 18 hours after termination of abciximab and again after 1 week of twice-daily oral administration of study drug [27].
• Patients with stents were treated with aspirin, ticlopidine and a 60-h tapering heparin regimen [28].
• The patients were randomly assigned to either a cilostazol or ticlopidine group before stent placement [21].
• Ticlopidine hydrochloride, a new antiplatelet medication, has recently been approved for prescription in North America. We reviewed the major clinical trials of ticlopidine and derived guidelines for its use [29].

Gene context of TICLOPIDINE HYDROCHLORIDE

• The influence of ticlopidine on CYP2C9, the other cytochrome P450 isoform that metabolizes phenytoin, is relatively weak, with a calculated Ki of 38.8 +/- 27 mumol/L [24].
• Clopidogrel also inhibited CYP2C9, and ticlopidine also inhibited CYP1A2, with lower potency [30].
• Thus, although both compounds proved to be relatively potent inhibitors of CYP2B6, thioTEPA was about 2 orders of magnitude more selective than ticlopidine [31].
• We have shown that ticlopidine is a potent inhibitor of CYP2C19 (IC(50) = 4. 5 microM) and CYP2D6 (IC(50) = 3.5 microM) activities [32].
• In unstable angina patients, plasma levels of TF, TFPI and TFPI/FXa were more efficiently reduced by adjunct ticlopidine therapy compared with adjunct coumadin/dipyridamole [33].

Analytical, diagnostic and therapeutic context of TICLOPIDINE HYDROCHLORIDE

• In patients examined, these abnormalities resolved upon the remission that accompanied plasma exchange and discontinuation of ticlopidine therapy [34].
• METHODS AND RESULTS: We randomized 350 high-risk patients within 6 hours after stent implantation to receive during 30 days either aspirin 250 mg and ticlopidine 500 mg/d (A+T group) or aspirin 250 mg/d and oral anticoagulation (A+OAC group) targeted at an international normalized ratio of 2.5 to 3 [35].
• Two major factors exhibited time-dependent variations of their influence: while residual dissections were the dominant risk factor within the first 3 days with a reduction after that, no protective effect of ticlopidine could be identified before day 3 [36].
• Thirty patients underwent PTCA; 15 of them were not treated with ticlopidine and 15 were given ticlopidine (> or = 72 h) [13].
• METHODS: Published data from trials and registries that compared clopidogrel with ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed [37].

References