Nowadays, PHOSPHODIESTERASE inhibitors (such as Sildenafil, Tadalafil, Vardenafil, and Avanafil) are used to treat erectile dysfunction in men and pulmonary arterial hypertension. There have been numerous reported ocular side effects of these drugs including anterior ischemic neuropathy, central serous chorioretinopathy, retinal hemorrhage, retinal vein occlusion, and retinal artery occlusion. Also, after taking PHOSPHODIESTERASE inhibitors, various subjective vision complaints, such as Cyanopsia, blurred vision, diplopia, and photopsia are expressed by patients. We extensively searched PHOSPHODIESTERASE inhibitors ocular side effects in the literature, using PubMed and Medline. In this review article, we classified the ocular side effects of these drugs and the controversies in the reports, the mechanism of action, paraclinical findings, as well as animal studies in this field.

PHOSPHODIESTERASE type 5 inhibitors such as sildenafil citrate and tadalafil are well known for the treatment of erectile dysfunction. However, their use in the presence of pulmonary hypertension can cause ophthalmologic side effects, including non-arteritic optic ischemic neuropathy, chorioretinopathy, glaucoma, and optic atrophy. The present review aimed to identify these visual side effects and provide recommendations. We identified articles published from January 2000 to March 2019 on diseases arising from the management of sexual dysfunction in urology or pulmonary hypertension in pneumonia that could cause pathologic alterations in eye structure based on a literature search of the MEDLINE electronic database using keywords for the most common adverse effects and different kinds of PHOSPHODIESTERASE 5 inhibitors. After applying the exclusion criteria, we selected 36 of the 77 articles initially identified to write the narrative review and added 20 additional articles to completely describe the pathological entities. PHOSPHODIESTERASE type 5 inhibitors can cause side effects in the eye including ocular surface abnormalities, increased intraocular pressure and glaucoma, uveitis, non-arteritic ischemic neuropathy, chorioretinopathy, retinal occlusion, and visual field changes. There is an increased need for well-performed studies to better understand these side effects, which are common due to the wide use of sildenafil.

Background: Three selective and most used inhibitors of PDE-5-sildenafil, vardenafil and tadalafil-have been successfully used for the treatment of erectile dysfunction. Erectile dysfunction and cardiovascular dis-eases might be considered as two dissimilar clinical signs of the identical systemic disease. PDE-5 inhibitors can through different models and mechanisms induce vasodilation, decrease apoptosis and cell proliferation, and they are widely present in various tissues that make them promising targets in a range of cardiovascular diseases. Methods: PubMed was explored to identify papers published from 1990-2019, presenting data for the most used PDE-5 inhibitors (sildenafil, tadalafil or vardenafil) in treatment of cardiovascular diseases. Results: This article analyses the therapeutic potentials of PDE-5 inhibitors in cardiovascular diseases and discusses mechanisms, possible risks and limitations. Comparable to earlier studies, newer studies suggest car-dioprotective effects of PDE-5 inhibitors, which include different models and mechanisms and do not indi-cate an increased rate of significant cardiovascular adverse reactions. Dissimilarity in the pharmacokinetics and pharmacodynamics of PDE-5 inhibitors are significant to their risk-benefit profile and clinical use. Some of the studies suggesting infarct size reduction after PDE-5 inhibition described the especially close dose-effect relation, other studies dosage adaptation in drug-drug interactions. Conclusion: PDE-5 inhibitors indicate the encouraging useful effects by ischemia/reperfusion injury, myocar-dial infarction, cardiac hypertrophy, cardiomyopathy and systolic and diastolic congestive heart failure. There-fore, this and similar reviews can help for additional clinical targeting in the therapy of cardiovascular diseases.

Purpose: One of the promising chemical groups for the development of new antihypertensive medicines, the action of which is associated with the inhibition of PHOSPHODIESTERASE III (PDE3) activity, are phosphorylated oxazole derivatives (OVPs). This study aimed to prove experimentally the presence of the OVPs antihypertensive effect associated with decreasing of PDE activity and to justify its molecular mechanism. Methods: An experimental study of the effect of OVPs on PHOSPHODIESTERASE activity was performed on Wistar rats. Determination of PDE activity was performed by fluorimetric method using umbelliferon in blood serum and organs. The docking method was used to investigate the potential molecular mechanisms of the antihypertensive action of OVPs with PDE3. Results: The introduction of OVP-1 50 mg/kg, as a leader compound, led to the restoration of PDE activity in the aorta, heart and serum of rats with hypertension to the values observed in the intact group. This may indicate the possibility of the development of vasodilating action of OVPs by the influence of the latter on the increase in cGMP synthesis due to inhibition of PDE activity. The calculated results of molecular docking of ligands OVPs to the active site of PDE3 showed that all test compounds have a common type of complexation due to phosphonate groups, piperidine rings, side and terminal phenyl and methylphenyl groups. Conclusion: The analysis of the obtained results both in vivo and in silico showed that phosphorylated oxazole derivatives represent a new platform for further studies as PHOSPHODIESTERASE III inhibitors with antihypertensive activity.

Background: Pentoxifylline (PTX), a methylxanthine derivative and nonspecific type 5 PHOSPHODIESTERASE (PDE) inhibitor, is a drug widely used in the management of peripheral arterial disease.Objectives: The aim of this study was to investigate the possible protective role of PTX on toxicity of acrolein (ACR).Materials and Methods: In this experimental study, 30 male rats were equally divided in to 6 groups (5 rats each). Group I (control) that received normal saline, group II was given ACR (2 mg /kg/day, i.p.). Animals of group III received only PTX (50 mg/kg/day, i.p.). Group IV was given ACR + PTX, groups V received only vitamin E (15 mg/kg/day, s.c.) and group VI was given vitamin E combination to ACR once daily for 14 dayes. Oxidative damage were measured by oxidative biomarkers such as glutathione peroxidase (GPx), superoxide dismutase (SOD), lipid peroxidation (LPO) and total glutathione (GSH) in blood of rats.Results: At the end of the experiment, the plasma of the animals was separated. In the blood plasma, ACR reduced total glutathione (GSH), SOD and GPx compared control group. Also, the LPO was increased in the ACR group as compared with controls. PTX ameliorated LPO, SOD and GPx in blood of ACR-induced changes.Conclusions: These findings suggest that PTX may provide a promising approach for the treatment of ACR-related diseases throughout reduction oxidative injuries.