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Pulmonary Circulation
Published in Wilmer W Nichols, Michael F O'Rourke, Elazer R Edelman, Charalambos Vlachopoulos, McDonald's Blood Flow in Arteries, 2022
Nitric oxide, inhaled continuously, has been shown effective as a pulmonary vasodilator in primary and other forms of pulmonary hypertension (Krasuski et al., 2000) either alone or in association with sildenafil. Sildenafil alone has also proven effective as a pulmonary vasodilator (Zhao et al., 2001) and is currently being evaluated in acute and long-term studies. Other PDE5 inhibitors, including tadalafil and vardanefil, are also under study. Another vasodilator, tolazoline hydrochloride, an α-adrenergic receptor antagonist, has also been used in some patients to treat primary pulmonary hypertension. This agent decreases pulmonary artery pressure, wave reflection amplitude and characteristic impedance (Figure 13.21).
Dopamine Receptors, Signaling Pathways, and Drugs
Published in Nira Ben-Jonathan, Dopamine, 2020
Several PDE5 inhibitors, e.g., sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) are used to treat erectile dysfunction and have an excellent safety record [58]. Cialis is the longest acting of the three drugs and has been recently on clinical trials to treat head and neck cancer [59]. The main targets of cGMP are two kinases—PKG-I and PKG-II [60]—both of which are inhibited by KT5823. The PKG-I gene is expressed as cytosolic PKG-Iα or PKG-Iβ isoform, while the PKG-II gene is expressed as a membrane-associated PKG-II protein. The kinetics, localization and substrates of the PKG enzymes differ. The PKGs phosphorylate many downstream effectors, some of which overlap with those that are targeted by PKA, while others are distinct. In many, but not all, cell types, activated PKG leads to the suppression of cell proliferation and/or apoptosis.
Erectile dysfunction and Peyronie’s disease
Published in J Kellogg Parsons, E James Wright, The Brady Urology Manual, 2019
Trinity J Bivalacqua, Mohamad E Allaf
PDE5 inhibitor therapy is highly efficacious and improves erectile function in a broad population of men with ED, including hard-to-treat patients with severe diabetes mellitus and following radical retropubic prostatectomy.22
PDE1 inhibitors: a review of the recent patent literature (2008-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Mei-Ling Le, Mei-Yan Jiang, Chuan Han, Yi-Yi Yang, Yinuo Wu
Phosphodiesterases (PDEs) are a super-enzyme family in charge of hydrolyzing the second messages cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are encoded by 21 genes and classified into 11 subfamilies based on their cloning and functional characterization [1,2]. PDE5, 6, and 9 specifically hydrolysis cGMP, while PDE4, 7, and 8 specifically hydrolysis cAMP. The other subfamilies include PDE1, 2, 3, 10, and 11 hydrolysis cAMP and cGMP simultaneously [3]. As cAMP and cGMP exert significant effects on physiological functions, PDEs work as novel therapeutic targets for many diseases and some PDE inhibitors have already been approved in the market [4,5]. For example, PDE5 inhibitors, such as sildenafil and tadalafil, are used for the treatment of human erectile dysfunction and pulmonary arterial hypertension [6–8]. PDE4 inhibitors, such as roflumilast and apremilast, are used for the treatment of chronic obstructive pulmonary disease and psoriasis, respectively [9,10].
Absorption, distribution, metabolism, and excretion of [14C]TPN729 after oral administration to rats
Published in Xenobiotica, 2022
Huan Cheng, Jinghua Yu, Chen Yang, Ning Zhang, Zhen Fan, Xiaojuan Zhang, Junchen Wang, Zhen Wang, Da-fang Zhong, Ji-Xiang He, Shu Yan, Xingxing Diao
Erectile dysfunction (ED) is a common medical problem that is frequently overlooked by clinicians, but has a profoundly negative impact on individuals’ quality of life (Christensen et al. 2011; Grant et al. 2013). Currently, phosphodiesterase type 5 (PDE5) inhibitors, as first-line therapies, are widely used in the treatment of ED. Sildenafil, vardenafil, tadalafil, and avanafil, which are the four PDE5 inhibitors currently approved by the US FDA, have been accepted worldwide. Sildenafil was the first oral PDE5 inhibitor approved in 1998, followed by vardenafil and tadalafil in 2003 and avanafil in 2012 (Gao et al. 2015; Andersson 2018). These drugs effectively improve erectile function and quality of life for many people around the world. However, some adverse effects, including visual disturbances, back pain, myalgia, flushing, dyspepsia, and so on (Uckert et al. 2013), have also been observed, resulting in the discontinuation of treatment.
Recurrent priapism in spinal cord injury: A case report
Published in The Journal of Spinal Cord Medicine, 2021
Engin Koyuncu, Özlem Taşoğlu, Ali Orhan, Sibel Özbudak Demir, Neşe Özgirgin
Low dose phosphodiesterase type 5 (PDE5) inhibitors (Sildenafil 25 mg/day or tadalafil 5 mg/day) can also be used in the treatment of recurrent priapism. Although these agents are routinely used in erectile dysfunction, in low doses they have a paradoxical effect preventing priapism.1 It is understood that PDE5 enzyme dysregulation plays a role in the pathophysiology of priapism. As a result of PDE5 dysregulation, cGMP increases and causes overt vasorelaxation in erectile tissues leading to priapism. Low doses of long-lasting PDE5 inhibitors allows normal active secretion of PDE5 and cGMP breaks down effectively. As a result, priapism is prevented. PDE5 inhibitors should be started when penis is not erected.10 Other agents used in the treatment of recurrent priapism are; hormonal therapies (gonadotropin-receptor hormone agonists and antagonists), antiandrogens (flutamide, bicalutamide), oestrogens, 5-alpha reductase inhibitors, ketoconazole, digoxin, alpha adrenergic agonists (pseudo-ephedrine, etilefrine), gabapentine, terbutaline and hydroxyurea. But except the oral and intrathecal forms of baclofen, the above mentioned agents are not demonstrated to be efficacious in SCI.1,6 They may be used in unique cases where oral/intrathecal baclofen fails. Moreover, antiandrogen agents may not be suitable in chronic SCI because of the high prevelance of androgen deficiency and hypogonadism in chronic SCI males.11–14