Antiplatelet Therapy
Hau C. Kwaan, Meyer M. Samama in Clinical Thrombosis, 2019
Its dose-effect relationship is particularly marked for bleeding time which can be greatly prolonged, much more than with aspirin.76 However, individual susceptibility seems somewhat variable and the recommended standard dosage of 250 mg b.i.d. may not be sufficiently effective. Ticlopidine is active in many experimental models of thrombosis. It does not impede the accumulation of labeled platelets in vascular prosthesis,79 but can normalize shortened platelet survival in atherosclerotic patients.80 It should not be given in association with aspirin, other nonsteroidal antiinflammatory drugs, or oral anticoagulants. Ticlopidine has been observed to produce several cases of severe cytopenia which have been published and seem traceable to the drug. These are mainly cases of agranulocytosis, occurring within the first 3 weeks of treatment. This complication is usually reversible on discontinuation of the drug. Even though recent analysis of several therapeutic trials81 did not reveal a noticeable increase in the incidence of hematological toxicity with ticlopidine vs. placebo, it is wise to monitor the blood counts especially at the beginning of treatment. The most frequent side effect encountered is diarrhea,75,81 and occasionally allergic skin reactions have been observed.
Management of peripheral arterial disease in the elderly
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Antiplatelet drugs that have been shown to decrease the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in persons with PAD are aspirin, ticlopidine, clopidogrel, and ticagrelor (120–122). Aspirin plus dipyridamole has not been shown to be more efficacious than aspirin alone in the treatment of persons with PAD (120). Oral platelet glycoprotein IIb/IIIa inhibitors have been shown to increase mortality in the treatment of persons with CAD and have not been investigated in the treatment of persons with PAD (123). Adverse hematologic effects associated with ticlopidine limit the use of this drug in the treatment of elderly persons with PAD (124). Ticagrelor and clopidogrel are equally effective in reducing cardiovascular events and cause a similar incidence of major bleeding (122).
Bronchiolitis obliterans organizing pneumonia induced by drugs or radiotherapy
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Ticlopidine is a platelet aggregation inhibitor used as a preventive agent in patients with temporal arteritis, strokes or transient ischaemic attacks. A 76-year-old woman was taking prednisone 45 mg daily, plus ticlopidine 250 mg twice daily, for giant-cell temporal arteritis.57 In 1 month she developed a pruritic skin rash, increasing shortness of breath and bilateral crackles. The chest radiograph showed diffuse bilateral peripheral infiltrates. Transbronchial biopsy showed air-spaces filled with organizing connective tissue plugs consistent with BOOP. The ticlopidine therapy was stopped. Prednisone was continued. The dyspnoea and blanching cutaneous lesions improved. Shortness of breath with exertional activities disappeared in 3 months and the interstitial radiographic pattern had resolved at 5 months.
Nanotechnological approach to delivering nutraceuticals as promising drug candidates for the treatment of atherosclerosis
Published in Drug Delivery, 2021
Sindhu C. Pillai, Ankita Borah, Eden Mariam Jacob, D. Sakthi Kumar
Anti-thrombotic therapy is a sought-after treatment option for thrombosis that underlies acute coronary syndrome. The appropriate management of reduction in platelet aggregation is warranted for anti-thrombotic drugs. Aspirin is one of the keystone anti-thrombotic drugs that has been demonstrated to reduce fatal and non-fatal risk of myocardial infarction in at least 50% of patients. Aspirin interferes with the formation of thromboxane A2 and reduces platelet aggregation via the blockade of the cyclo-oxygenase pathway. A beneficial dose of 75–50 mg seems to have a sustained effect with lower side effects related to gastrointestinal conditions (Watson et al., 2002). Clopidogrel and Ticlopidine belong to the adenosine diphosphate (ADP) inhibitors class of anti-thrombotic drugs (Sharis et al., 1998). Ticlopidine has previously been shown to reduce infarction, stroke, and angina for at least six months nonetheless associated with reversible neutropenia and thrombocytopenia. Clopidogrel represents the advanced derivative version of ticlopidine which is highly effective in reducing platelet aggregation. Clopidogrel also reports decreased risk of bleeding than aspirin and has better tolerability. Anti-thrombotic therapy additionally comprises of other strategies such as glycoprotein IIb/IIIa receptor inhibitors, anti-coagulant therapy (heparin treatment and fibrinolytic treatment) that has elucidated varied results in patients of the acute coronary syndrome in different experimental settings (Watson et al., 2002).
Successes, failures, and future prospects of prodrugs and their clinical impact
Published in Expert Opinion on Drug Discovery, 2019
Platelet aggregation inhibitors are crucial to the management of clotting disorders and to the prevention and follow-up treatment of strokes and cardiovascular incidents. Clopidogrel [22], prasugrel [23], and dabigatran etexilate are prodrugs amongst the most prescribed agents in this class. Clopidogrel and prasugrel are adenosine diphosphate (ADP) receptor blockers while dabigatran etexilate is a direct thrombin inhibitor. Clopidogrel is activated by two-step CYP450 metabolism to furnish its active form. Similarly, prasugrel is hydrolysed by human carboxylesterase 2 (hCE2) to R-95913 and then metabolized to yield R-138727, the active form [24]. Ticlopidine is another prodrug in this therapeutic group. It is an older agent that also inhibits adenosine diphosphate receptors. Though, its use in the daily treatment is limited due to serious side effects such as neutropenia and thrombotic thrombocytopenic purpura.
Ticagrelor improves systemic immune-inflammation index in acute coronary syndrome patients
Published in Acta Cardiologica, 2022
Mehmet Koray Adali, Ipek Buber, Oguz Kilic, Anil Turkoz, Samet Yilmaz
Recently, in a PLATO substudy investigating the effect of clopidogrel and ticagrelor on leukocyte counts has been found lower WBC counts in ACS patients treated with clopidogrel. This effect of clopidogrel on WBC is independent of baseline biomarkers and clinical risk factors and is consistent across the one-, three- and six-month timepoints [12]. Thienopyridines have been associated with bone marrow suppression. Ticlopidine has been limited for clinical use due to this side effect. Clinically apparent leukopenia is rare with clopidogrel, and this slight decrease may be considered as a group effect of thienopyridines. Similarly, in the present study, we found a decrease in WBC in the CG during the follow-up period compared to the TG.
Related Knowledge Centers
- Adenosine Diphosphate
- Drug Discovery
- Thrombotic Thrombocytopenic Purpura
- Ticagrelor
- Neutropenia
- Medication
- Clopidogrel
- Indication
- P2Y12
- P2Y Receptor