China
Africa
Explore chapters and articles related to this topic
Role of Eicosanoids in Renal Disease
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
The interplay between vasoconstrictor and vasodilator PGs is illustrated by differences in renal function after treatment with indomethacin and specific thromboxane synthase inhibitors. Chronic administration of the thromboxane inhibitors OKY-1581 (O’Neill et al., 1990) or FCE22178 (Zoja et al., 1990) caused improvements in glomerular filtration rate, renal blood flow, proteinuria, mean arterial pressure, and histology with a concurrent reduction in urinary thromboxane excretion. Acute thromboxane inhibition with UK38485 also improved glomerular filtration rate and reduced elevated glomerular production of thromboxane without inhibiting PGE2 production (Stahl et al., 1986). Chronic aspirin administration at a dose which decreased thromboxane in the serum, but not in glomeruli or urine, had no effect on the abnormal renal function and structure that occurs in the remnant kidney (Zoja et al., 1989). The pathophysiologic role of thromboxane in this model, however, is not without controversy, because chronic administration of a thromboxane receptor antagonist, daltroban, did not have a beneficial effect on renal function (Brooks et al., 1990).
Drug Combinations
Published in Josef Hladovec, Antithrombotic Drugs in Thrombosis Models, 2020
Hanson et al.71 found no potentiation of dipyridamole or sulfinpyrazone effects by dazoxiben in their baboon A/V-shunt model as reflected by platelet consumption. Smith and Egan72 observed some inhibition of thrombin-induced DIC in rabbits by the combination of a phosphodiesterase inhibitor with a thromboxane synthetase inhibitor or with ASA.73 The combination with prostacyclin was also effective. According to de Gaetano et al.2 thromboxane synthesis inhibitors could be used with advantage in combination with ASA whereas the combination with dipyridamole affords no benefit.74 On the other hand, the combination with thromboxane receptor blocking agents looks particularly logical.75 Heparin may be successfully combined with prostacyclin to inhibit the coagulation pathway e.g., in venous thrombosis but not in arterial thrombosis.58
Antiplatelet Therapy
Published in Hau C. Kwaan, Meyer M. Samama, Clinical Thrombosis, 2019
T. Lecompte, M. M. Samama, Hau C. Kwaan
In light of our knowledge, several logical combinations can be proposed, some of which have already been tested in vivo, but none of which has, so far, been clinically studied for efficacy and bleeding risk on a long-term basis. Among these combinations are (1) aspirin or another inhibitor of the thromboxane pathway plus ticlopidine;76 (2) a thromboxanesynthetase inhibitor, or a prostacyclin analog plus a cAMP-phosphodiesterase inhibitor;15,16 (3) a thromboxane-synthetase inhibitor plus an endoperoxide and thromboxane (receptor) antagonist.82,83
Physiological and pathophysiological roles of hepoxilins and their analogs
Published in Drug Metabolism Reviews, 2023
Sara A. Helal, Fadumo Ahmed Isse, Samar H. Gerges, Ayman O. S. El-Kadi
In agreement with these results, the effect of PBT-3 was compared to two thromboxane receptor antagonists SQ 29,548 and pinane thromboxane A2. The three compounds exhibited an antiplatelet effect in an ex vivo model but with different potencies. Interestingly, PBT-3 showed a high degree of specificity among other HxA3 and HX analogs when tested using a PFA-100-platelet function analyzer. It significantly prolonged the closure time in membranes coated with collagen/epinephrine in which platelet-related hemostasis is simulated (Reynaud et al. 2003). Albeit all four hepoxilin analogs (PBT-1 to PBT-4) can inhibit the aggregation of human platelet in vitro, it is obvious that PBT-3 is the most active with a 500-fold greater effect than the native HX (Reynaud et al. 2001). These results can make PBT-3 a worthy candidate for investigating new intervention strategies against diseases involving enhanced thromboxane production and platelet aggregation such as septic shock, thrombosis, and diabetes mellitus.
The antithrombosis effect of dehydroandrographolide succinate: in vitro and in vivo studies
Published in Pharmaceutical Biology, 2022
Bowen Yin, Shuhua Zhang, Yuxi Huang, Yuanzhu Long, Yiguo Chen, Shiyun Zhao, Aiqun Zhou, Minghua Cao, Xiaoming Yin, Daya Luo
In current clinical treatment, certain side effects have been observed during the use of commonly employed antiplatelet agents for targeted primary hemostasis, such as thrombin inhibitors, ADP receptor inhibitors, and cyclooxygenase (COX) inhibitors. For example, because of the non-selective inhibition of COX by aspirin, low reactivity, serious side effects, gastrointestinal haemorrhage, and other problems may occur during treatment (Group et al. 2018). The thromboxane receptor inhibitor terutroban exerts a secondary preventive effect on patients with thrombotic cerebral ischaemia, but the haemorrhagic side effects of terutroban are still slightly higher than those of aspirin (Bousser et al. 2011; Lee and Ovbiagele 2011). Clopidogrel also has the problem of low reactivity and bioavailability in some patients. Aspirin combined with clopidogrel is often used for antiplatelet aggregation therapy; however, the risk of haemorrhage has not been effectively improved (Yusuf et al. 2001; Bates et al. 2011; Katsanos et al. 2015), and in some patients, this treatment also causes problems such as decreases in the numbers of neutrophils and platelets and aplastic anaemia (Maurício et al. 2014). Therefore, demand for antiplatelet aggregation drugs with high efficiency, low toxicity, a low haemorrhage risk, and low prices in clinical practice is still great.
Platelets and viruses
Published in Platelets, 2021
Silvio Antoniak, Nigel Mackman
Platelets are released by megakaryocytes in large numbers into the blood[1]. The main function of these small anucleate cells is to maintain vascular integrity after injury of the vasculature. Uncontrolled platelet activation can also lead to thrombosis. Platelets contain receptors that mediate adhesion to the damaged vessel wall, such as glycoprotein (GP) Ib-V-IX, GPVI and α2β1, and receptors that respond to soluble agonists, such as P2Y12, thromboxane receptor and protease-activated receptor (PAR) 1 and 4[2]. Platelets contain three different types of granule. Dense (δ) granules contain mediators that regulate vascular tone, such as nucleotides (e.g. ADP and GTP), bioactive amides (e.g. histamine and serotonin) and bioactive ions (e.g. Ca2+ and PO3−). Alpha (α) granules contain proteins that can be classified into five groups: adhesion molecules, platelet microbicidal proteins and kinocidins, mitogenic factors, coagulation factors and protease inhibitors. Finally, lysosomal (λ) granules contain enzymes, such as proteases and glycosidases, that can modulate platelet-fibrin retraction needed for wound healing[3]. A variety of platelet inhibitors, including acetylsalicylic acid (ASA) and P2Y12 receptor antagonists, are used to prevent arterial thrombosis[2].