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Analgesics during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
The main use of aspirin has been as an analgesic, antipyretic, or anti-inflammatory agent. Salicylates were used clinically for over 120 years and are one of the most commonly used nonnarcotic analgesics. Aspirin has been widely used in pregnancy in the past, but acetaminophen has supplanted ASA as the most frequently used analgesic in pregnancy. Prospective study of 1529 pregnant women in 1974 and 1975, reported an estimated 50 percent of the women took aspirin sometime during pregnancy, but less than 5 percent took the drug daily. Salicylates are prostaglandin synthetase inhibitors, and non-selectively inhibit cyclooxygenase (COX) enzymes 1 and 2. COX-1 inhibition blocks normal production of protective esophageal and gastric mucosa, increasing the risk for gastrointestinal bleeds and associated complications. COX-1 suppression blocks synthesis of prostacyclin and thromboxane A (vasoactive prostaglandins). Prostacyclin is a strong vasodilator that is a platelet aggregation inhibitor. Thromboxane A is a potent vasoconstrictor that stimulates platelet aggregation (Bhagwat et al., 1985; Ellis et al., 1976). Prostaglandin E and prostaglandins are also inhibited. COX-2 suppression possesses analgesic activity associated with blocking prostaglandins linked with inflammation.
Upper Urinary Tract Obstruction
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Phase II (90 min−5 hours) − decrease in RBF but continued increase in UP.The continued increase in UP and short-lived afferent arteriolar dilatation is followed by a prolonged post-glomerular/efferent arteriolar constriction, again attempting to prevent a fall in the GFR.Vasoconstrictors involved:Angiotensin II (ATII) − released via the RAS.Thromboxane − derived from inflammatory cells.Endothelin − released in response to the stretching of the endothelium.
Eicosanoids and Hypertension in Pregnancy
Published in Murray D. Mitchell, Eicosanoids in Reproduction, 2020
Scott W. Walsh, Valerie M. Parisi
We believe that therapy directed against selective thromboxane inhibition is, presently, the most promising with respect to the future treatment of preeclampsia and other hypertensive disorders of pregnancy. We encourage increased clinical trials with low-dose aspirin and other means of selective thromboxane inhibition.
Augmentation by resveratrol of the inhibitory effect of ethanol on platelet aggregation
Published in Platelets, 2023
Kazumi Ekawa, Mikio Marumo, Ichiro Wakabayashi
There is also an inconsistency in the findings of this study regarding thrombin-induced platelet aggregation and thromboxane A2 production: Resveratrol (3.125 µM) inhibited thrombin-induced thromboxane B2 formation (Table I) but not platelet aggregation (Figure 2). In fact, thromboxane B2 formation was reduced by 67% in the presence of resveratrol. This means that residual 33% or less of thromboxane A2 production was sufficient for causing platelet aggregation when stimulated with thrombin at the concentration used. These results agree with the results of a previous study showing that thrombin-induced aggregation was not affected by 13-azaprostanoic acid, a specific antagonist of thromboxane A2/endoperoxide receptors [28]. Further studies are therefore needed to clarify how thromboxane A2 is involved in platelet aggregation using different concentrations of thrombin and different kinds of agonists of platelets.
Emerging drugs for the treatment of diabetic nephropathy
Published in Expert Opinion on Emerging Drugs, 2022
Yoon Kook Kim, Xinyuan Ning, Kashif M. Munir, Stephen N. Davis
SER150 is an inhibitor of thromboxane synthase and thromboxane prostanoid receptor with proposed anti-inflammatory effects [96]. This agent is proposed to specifically attenuate the inflammatory processes in the renal vasculature, thereby reducing the damage to the kidneys related to prolonged hyperglycemia [97]. In an in vitro study, SER150 showed inhibitory effects on TNFα-induced endothelial inflammation and proliferation related to overdriven thromboxane pathway [98]. In addition, despite its effect on thromboxane synthase, it has not shown any increased bleeding events [99]. In a previous phase 2a study conducted with a much higher dosage of 300 mg, SER150 (formerly EV-077) showed signals of hepatotoxicity, which curbed the enthusiasm for this drug at the time. However, in a more recent phase 2a study using a much lower dose of 15–30 mg of SER150, no significant safety issues have been noted, and a strong trend toward reduction in urinary protein excretion has been reported by its developers [97].
Preeclampsia: state of art and future perspectives. A special focus on possible preventions
Published in Journal of Obstetrics and Gynaecology, 2022
Özge Kahramanoglu, Antonio Schiattarella, Oya Demirci, Giovanni Sisti, Franco Pietro Ammaturo, Carlo Trotta, Federico Ferrari, Agnese Maria Chiara Rapisarda
It is thought that changes in prostaglandin synthesis play a key role in microvascular dysfunction in PE. Thromboxane, which causes vasoconstriction and platelet aggregation, is increased while prostacyclin, which has the opposite effects, is reduced. The microvascular dysfunction is also due to an increased sensitivity to angiotensin II and the related augmented vasoconstriction. While normal pregnant women have insensitivity to vasopressor infusion, higher levels of angiotensin II have been shown in preeclamptic pregnant women (Lumbers et al. 2019). Various studies have shown that inhibition of angiotensin II type 1 receptor agonistic autoantibodies (AT1-AAs) could be another cause of this condition resulting in reduced uterine perfusion pressure (Vaka et al. 2020). Also, vascular cell adhesion protein 1 (VCAM-1) and fibronectin levels are increased in preeclamptic women compared to physiological pregnancy levels (Madazli et al. 2000).