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Cardiac Emergencies in Obstetrics
Published in Sanjeewa Padumadasa, Malik Goonewardene, Obstetric Emergencies, 2021
Sanjeewa Padumadasa, Sanjeewa Rajapakse
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are contraindicated in pregnancy due to fetal toxicity causing neonatal renal failure. However, these can safely be administered during breastfeeding. In women with AF, treatment with beta-blockers and digoxin, and anticoagulation to minimise the risk of thromboembolism, should be considered. In women with heart failure due to pulmonary hypertension, phosphodiesterase type 5 inhibitors such as sildenafil or tadalafil and prostaglandin therapy improve maternal survival. Endothelin receptor antagonists are contraindicated due to teratogenic effects.
Heart disease
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
PAH-targeted therapies should be continued in pregnancy. Specific therapies include: – Phosphodiesterase inhibitors (sildenafil, tadalafil). These can be safely continued or instigated in pregnancy.– Endothelin receptor antagonists (bosentan, ambrisentan). These are usually discontinued in pregnancy, as they are teratogenic in rats.– Prostanoid analogues (epoprostenol – intravenous [i.v.], iloprost – nebulized or i.v.) and nitric oxide – inhaled. These can be safely continued or instituted in pregnancy.
The benefits and risks of androgen therapy in the aging male: prostate disease, lipids and vascular factors
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
Among the most significant vasoactive substances are the endothelins. Endothelins are a family of peptides which are produced in a variety of tissues where they act as modulators of vasomotor tone, cell proliferation and hormone production. Studies with endothelins and specific endothelin-receptor antagonists have suggested that these peptides are important in vascular physiology and disease. Endothelin should be regarded more as a paracrine than as an endocrine hormone. The production of endothelins is regulated by a variety of hormones, other vasoactive substances and conditions of vascular stress. Endothelin-1 probably has a role in the maintenance of basal vasomotor tone and it is a very potent vasoconstrictor, counteracted by nitric oxide, prostacyclin and atrial natriuretic peptide. It is likely that endothelin-1 plays a role in atherosclerosis and cardiac hypertrophy (for review see Levin, reference 34).
Pharmacological management of youth with type 2 diabetes and diabetic kidney disease: a comprehensive review of current treatments and future directions
Published in Expert Opinion on Pharmacotherapy, 2023
Kalie L. Tommerdahl, Alexander J. Kula, Petter Bjornstad
Endothelin receptor antagonists (ERA) primarily target the endothelin A (ETA) receptor, which have demonstrated kidney protective effects. The ERA atrasentan attenuated DKD progression in adults with T2D in the “Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR)” trial [118]. Unlike SGLT2 inhibitors, ERAs increase sodium and fluid retention, leading to increased body weight and hemodilution (decreased hematocrit and hemoglobin), as well as edema, and a higher risk of developing heart failure [119,120]. This has limited the development and widespread use of agents in this class, especially in people who are predisposed to volume overload, including individuals with DKD. Indeed, a large randomized controlled trial in people with T2D and DKD using a relatively nonselective ERA avosentan was terminated early because of an increased frequency of heart failure [119]. In addition, despite the precautionary approach taken in the SONAR trial with atrasentan, including the use of diuretics and exclusion of people with heart failure or high BNP concentrations, there was a higher rate (3.5% versus 2.6%) of heart failure hospitalizations with atrasentan [118]. There are no ERA trial data in young persons with T2D. Although ERA holds promise as a therapy for T2D and DKD, it is unclear whether the benefits would outweigh risks, and it is likely best used in combination with a natriuretic or diuretic agent.
Adjuncts to pulsed dye laser for treatment of port wine stains: a literature review
Published in Journal of Cosmetic and Laser Therapy, 2021
Bing Wang, Xianglin Mei, Yanlong Wang, Xin Hu, Fuqiu Li
Endothelin is a bioactive peptide synthesized by endothelial cells that has vasoconstrictive effect, which is associated with the growth of various tumors. It can inhibit cell apoptosis and promote neovascularization. Endothelin receptor antagonists have been shown to exhibit antiangiogenic effects in animal models (47). Accordingly, some scholars speculated that the endothelin receptor antagonist, bosentan, may inhibit PDL-induced angiogenesis in PWS lesions. Under this assumption, it was used in combination with PDL to treat PWS. Four patients with refractory PWS received bosentan 1 day before the PDL treatment and continued it for 14 days. Three patients showed no or only slight improvement, whereas one patient showed a noticeable improvement at the treated area. At 6-month follow-up, the efficacy was maintained. Subsequently, this patient was continued to be treated, and the lesions also showed blanching. This result indicates that some PWS patients may benefit from systematically administered endothelin receptor antagonists to inhibit angiogenesis after PDL treatment (48).
The potential for immune checkpoint modulators in cerebrovascular injury and inflammation
Published in Expert Opinion on Therapeutic Targets, 2021
Jennifer E. Kim, Kisha Patel, Christopher M. Jackson
Therapies targeting the inflammatory cascade have not yet been successfully integrated into the standard aSAH treatment regimen. Nonspecific agents such as steroids, cyclosporine A, and non-steroidal anti-inflammatory drugs (NSAIDs) have had variable success in experimental and clinical trials [154]. Endothelin receptor antagonists that inhibit Endothelin-1 (ET-1) activity also showed initial promise; however clinical trials failed to demonstrate significant outcome benefits [155–159]. Emerging data suggest that immune checkpoints may play a role in aneurysm formation and complications post-hemorrhage. Zhang et al. have published a series of papers associating impaired upregulation of Tim-3 on Tregs with the formation of intracranial aneurysms although the pathogenic mechanism has not yet been elucidated [160–162]. More recently, we found that PD-L1 administration prevented vasospasm in a murine model and this therapeutic effect was abrogated by pretreatment with PD-1 blocking antibodies. Furthermore, changes in PD-1 expression on circulating monocytes predicted TCD elevations and development of clinical vasospasm in a series of aSAH patients [163]. Taken together, these findings implicate PD-1+ monocytes a novel biomarker and therapeutic target for cerebral vasospasm following aSAH, and supports further study of immune checkpoints as mediators of monocyte function during the subacute phase of cerebrovascular injury.