One mechanism of sudden sensorineural hearing loss after sildenafil and sexual activity.

OBJECTIVES: A case of sudden sensorineural hearing loss following use of sildenafil was examined in detail over a period of three days from first report to recovery. DESIGN: Case study. The subject presented with sudden sensorineural hearing loss and diplacusis a day after onset. Testing involved detailed interview, standard audiometry, detailed inter-octave audiometry, and measurement of detailed psychophysical frequency tuning curves during a two day recovery period. STUDY SAMPLE: One male aged in his thirties with otherwise normal hearing. RESULTS: Although standard audiometry was within normal limits, detailed inter-octave audiometry and psychophysical frequency tuning curves were consistent with a punctate unilateral intra-cochlear lesion that resolved over a period of three days. CONCLUSIONS: This is the first report of such a frequency-specific audiometric shift and diplacusis after sildenafil, and is not consistent with previous reports of direct ototoxic pharmacological effects. We propose that the lesion was most likely caused by a cochlear bleed, and may have been due to physical exertion rather than a direct pharmaceutical effect. The study highlights the important role of additional diagnostic testing that can be easily achieved in a clinical setting with minimal equipment.

Social Perceptions of Masculinity and Sexual Esteem Are Impacted by Viagra Use, Testosterone, and Sexual Performance.

Sexual behaviors play a role in the social construction of masculinity. Moreover, this stereotype has been capitalized upon by pharmaceutical companies, as well as those that sell products not approved by the U.S. Food and Drug Administration, for purposes of marketing sexual medicines. Stereotypical notions of masculinity, however, also emphasize the importance of self-reliance, which may cause some to look unfavorably upon the use of sexual medicine. Consistent with this notion, a male target was viewed as more masculine when his female partner consistently reached orgasm, unless he had no history of erectile dysfunction (ED), but was taking Viagra anyway (Experiment 1; N = 522). In addition, when his partner consistently reached orgasm, ratings of his sexual esteem were also lower if he used Viagra than if he did not, but only if he had no history of ED. In Experiment 2 (N = 711), although there was no effect of a male target's use of testosterone, social perception of his masculinity and sexual esteem increased as his "natural" levels of testosterone increased. In addition, exploratory analysis revealed that if the male target had low (but not normal or high) "natural" levels of testosterone, ratings of his masculinity were higher if his female partner consistently had an orgasm, which suggests that female orgasm served to "rescue" masculinity. Because expectations about drugs drive their use, it is important to address preconceived notions about the use of sexual medicines for purposes of enhancing masculinity and sexual esteem, as the social perception of their use is much more complex.

Utilization Trends of Phosphodiesterase Type-5 Inhibitors for Erectile Dysfunction Between 2019 and 2023 in Tanzania.

Introduction Erectile dysfunction (ED) profoundly affects millions of people globally, including interfering with mental health and quality of life. Phosphodiesterase type-5 inhibitors (PDE5Is) such as sildenafil are pivotal in ED treatment. This study aimed to examine the utilization patterns of PDE5Is in Tanzania. Materials and methods In this retrospective longitudinal study, data on sildenafil and other similar PDE5Is imported between 2019 and 2023 were sourced from the Tanzania Medicines and Medical Devices Authority (TMDA). Pre-processing and visualization were performed using Microsoft Power BI Desktop, and further analysis was performed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). Utilization trends were ascertained through curve fitting, Holt's linear trend model, and autoregressive integrated moving average (ARIMA) models. The defined daily doses (DDDS) per 1000 inhabitants (DID) were calculated using the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) Classification System and the DDD methodology endorsed by the WHO Collaborating Centre for Drug Statistics Methodology. Results Between 2019 and 2023, there was a pronounced increase in the importation of approximately 587 consignments of PDE5Is. Employing the Holt model (R-square = 0.843), a substantial increase from 0.220910 DID in 2019 to 0.534272 DID by 2025 was observed and anticipated. The period witnessed sildenafil dominating 75.5% of the total use, with Erecto being the most consumed brand (37.6% of total DID). Notably, 2022 had the highest surge (27.2% of the total), albeit a slight decline was observed in 2023 (20.5%). This trend was supported by a linear regression model (R-square = 0.889). Conclusion We found increasing annual trends of PDE5Is of utilization. This requires critical oversight and effective policies to ensure appropriate use and risk minimization.

Phosphodiesterase-5 inhibitors use and the risk of alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: The management of Alzheimer's disease (AD) poses considerable challenges, necessitating the pursuit of innovative therapeutic approaches. Recent research has spotlighted the promising role of phosphodiesterase type 5 inhibitors (PDE5Is) in reducing the prevalence of AD, utilizing their vasodilatory properties to suggest a potential neuroprotective effect. This meta-analysis and systematic review aims to assess the relationship between the use of PDE5Is and the risk of AD. METHODS: A detailed examination was carried out across several electronic databases till March 2024, including PubMed, Web of Science, Scopus, CENTRAL, and Embase. The focus was on identifying studies that compare the occurrence of AD among PDE5I users vs non-users. Through a random-effects model, pooled hazard ratios (HRs) were calculated, in alignment with guidelines from the Cochrane Handbook for Systematic Reviews and Meta-Analysis and the PRISMA standards. RESULTS: This analysis included six studies, cumulating a participant count of 8,337,313, involving individuals treated with sildenafil, tadalafil, and vardenafil, against a control group undergoing other or no treatments. The cumulative HR for AD risk among PDE5I users versus the control group was 0.53 (95% CI: 0.32-0.86, p = 0.008), signaling a markedly reduced likelihood of AD development in the PDE5I group. Particularly, sildenafil usage showed a significant risk reduction (HR: 0.46, 95% CI: 0.31-0.70, p < 0.001), while findings for tadalafil and vardenafil were not significant. Test of subgroup differences found no difference between male and female participants in the risk of AD. CONCLUSIONS: Our findings suggest that the use of PDE5Is is associated with a reduced risk of AD, highlighting its potential as a protective agent against neurodegenerative diseases. Given the very low quality of evidence and the heterogeneity among the included studies, further high-quality research is warranted to confirm these findings and elucidate the underlying mechanisms. Register number PROSPERO 2024: CRD42024522197.

Oral phosphodiesterase type 5 inhibitors and priapism: A VigiBase analysis.

PURPOSE: To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs). METHODS: We queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients. RESULTS: From a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively). CONCLUSIONS: PDE5i use shows disproportionate priapism signals which are higher in young patients.

Bioactive compounds from Cordyceps and their therapeutic potential.

The Clavicipitaceae family's largest and most diverse genus is Cordyceps. They are most abundant and diverse in humid temperate and tropical forests and have a wide distribution in: Europe, North America, and East and Southeast Asian countries, particularly: Bhutan, China, Japan, Nepal, Korea, Thailand, Vietnam, Tibet, and the Himalayan region of India, and Sikkim. It is a well-known parasitic fungus that feeds on insects and other arthropods belonging to 10 different orders. Over 200 bioactive metabolites, that include: nucleotides and nucleosides, polysaccharides, proteins, polypeptides, amino acids, sterols, and fatty acids, among others have been extracted from Cordyceps spp. demonstrating the phytochemical richness of this genus. These components have been associated with a variety of pharmacological effects, including: anti-microbial, anti-apoptotic, anti-cancer, anti-inflammatory, antioxidant, and immunomodulatory activities. In this paper, the bioactivity of various classes of metabolites produced by Cordyceps spp., and their therapeutic properties have been reviewed in an attempt to update the existing literature. Furthermore, one of its nucleoside and a key bioactive compound, cordycepin has been critically elaborated with regard to its biosynthesis pathway and the recently proposed protector-protégé mechanism as well as various biological and pharmacological effects, such as: suppression of purine and nucleic acid biosynthesis, induction of apoptosis, and cell cycle regulation with their mechanism of action. This review provides current knowledge on the bioactive potential of Cordyceps spp.

Solid state 13C NMR spectroscopy as a tool for identification of counterfeit Viagra tablets and guide for develop new identification approach of falsified product.

Counterfeit drugs are a global problem that is directly related to the safety and effectiveness of pharmacotherapy. The black market for counterfeit products is constantly growing and related to the wide availability through online shopping. Therefore, there is a constant need to develop analytical methods that would allow for the unambiguous identification of counterfeit products from the original ones. One of such techniques is solid-state NMR spectroscopy, which allows for direct registration and analysis of spectra of multicomponent solid forms of pharmaceutical formulations. The paper explores the possibility of using this technique in the identification of counterfeit Viagra tablets. In this study, solid-state NMR has been used to detect the non-pharmacopoeial cellulose present in the samples of counterfeit Viagra tablets. Besides, the NMR results allowed to develop a rapid dying technique that can be used to distinguish between the counterfeit and original drug. It has been shown that solid-state NMR spectroscopy allows for numerous analyses such as identification of counterfeit products, assessment of the composition of analyte, estimation of qualitative differences between the original and falsified product, and the development of simple analytical methods based on tablets composition differences.

A Systematic Review of Sildenafil Mortality Through the Years.

Sildenafil is a medication used for the treatment of erectile dysfunction. It was approved by the U.S. Food and Drug Administration (FDA) in 1998. Several articles have raised concerns regarding the use of sildenafil and the occurrence of serious adverse events, such as myocardial ischemia, stroke, and even death. Our aim is to systematically review the existing literature on mortality associated with sildenafil use. The method used for this systematic review was completed by searching three databases: PubMed, Scopus, and Web of Science. Articles were screened and assessed for eligibility. This review uses the articles found to address the concerns associated with sildenafil and mortality. A total of 19 reports were used in our systematic review, in which there were 10 case reports, two case series, three systematic reviews, one narrative review, one retrospective study, one article in the British Medical Journal, and one commentary article. One FDA article in particular included case reports and reports to the FDA on the use of sildenafil eight months after its introduction to the market in 1998, with 522 deaths reported. Another retrospective study examined the use of sildenafil on infants below the age of 1 who did not have congenital heart disease but did suffer from severe pulmonary hypertension. The study found a mortality rate of 29%, which increased with sildenafil dosage. A case series examined six deaths related to non-prescription use of sildenafil. All these cases were subjected to autopsies and related to sexual activity. The study suggests that phosphodiesterase 5 inhibitors induced the deaths, and the concentration of sildenafil in the femoral blood was found to be between 0.032and0.087 µg. To conclude, the literature available on this topic is deemed insufficient to provide enough data to establish a direct link of causality between sildenafil and mortality. Although some studies paint sildenafil as the culprit behind these deaths, further studies and research are needed to explain the unexpected deaths following sildenafil use.

Non-Arteritic Anterior Ischemic Optic Neuropathy Associated With the Use of Phosphodiesterase Type 5 Inhibitors: A Literature Review.

Phosphodiesterase type 5 (PDE5) inhibitors are frequently used for erectile dysfunction (ED) as the first line of treatment. This medication was initially developed to treat muscle spasms and pulmonary hypertension. The United States Food and Drug Administration (FDA) approved its usage for treating ED. Sildenafil, tadalafil, vardenafil, and avanafil are PDE5 inhibitors. The decrease of cyclic guanosine monophosphate (cGMP) in smooth muscle cells caused by sildenafil causes smooth muscle relaxation and penile erection. Vasodilation of the blood vessels reduces perfusion and blood flow to the optic nerve and eye. Several incidences of non-arteritic anterior ischemic optic neuropathy (NAION) have been recorded in sildenafil users, among other ocular complications. The onset of NAION is usually sudden and painless, and it is associated with any pattern of visual field loss. Possible symptoms include poor visual acuity, diminished color vision, a visual field defect, or hemorrhages in the form of flames. Nevertheless, NAION pathogenesis is still a mystery. Most visual effects are reversible weeks after the medication is stopped, and NAION does not seem to cause a permanent blindness. A small cup-to-disc ratio (disc at risk) and underlying systemic illnesses, such as hypertension, increase the risk of developing NAION. An early indicator of cardiovascular disease is ED. NAION diagnosis is challenging due to a lack of confirmatory diagnostic evidences. Normal visual acuity does not exclude NAION from being a possibility. In order to evaluate visual outcomes in NAION, data on both visual acuity (VA) and the full peripheral visual field are needed. Treatment with steroids did not seem to improve visual results.

Long-term follow-up of retinal morphology and physiology after 2000 mg sildenafil overdose as a means of attempted suicide: a case report.

BACKGROUND: Few case reports have described sildenafil overdose, particularly ingestion of > 1000 mg, and overdose-induced changes in visual function remain unclear. We report retinal morphology, retinal sensitivity, and findings of electrophysiological evaluation over long-term follow-up in a case of sildenafil overdose (2000 mg). CASE PRESENTATION: Our patient developed visual abnormalities in the paracentral visual field accompanied by photophobia, decreased contrast sensitivity, and difficulty distinguishing colors in both eyes, 8 hours after the sildenafil overdose. These symptoms did not improve throughout the course, and although abnormalities of retinal morphology and sensitivity, as well as the electroretinogram findings showed slight improvement, the patient did not recover completely at 6-month follow-up. CONCLUSIONS: We observed that high-dose sildenafil ingestion leads to retinal toxicity; the ocular abnormalities may persist for at least 6 months. Optical coherence tomography, Humphrey perimetry, microperimetry, and multifocal electroretinography are useful to quantitatively monitor temporal changes.

Psychosis beas a rare side effect of sildenafil: a case report.

BACKGROUND: Sildenafil citrate is a commonly used medication for the management of erectile dysfunction. Previous studies have described some neuropsychiatric side effects of this medication. So far, however, there has been little discussion about sildenafil-induced psychosis. CASE PRESENTATION: We here present the case of a 32-year-old Iranian male, without a known psychiatric history, who developed psychotic symptoms following initiation of sildenafil. We also postulate a mechanism by which this may occur. CONCLUSIONS: This report highlights the importance of watchful observation for the occurrence of this rare but serious side effect. Further studies are needed to clarify the precise mechanism that causes sildenafil-induced psychosis.

Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm.

Background cGMP-hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP-dependent protein kinase I (PKGI)-dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men. Methods and Results AAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3-aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre-existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA. Conclusions Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.

Sildenafil in ophthalmology: An update.

Sildenafil citrate, a selective oral phosphodiesterase 5 inhibitor, is a widely used drug for erectile dysfunction that acts by elevating cGMP levels and causing smooth muscle relaxation. It also has 10% activity against PDE6, a key enzyme in phototransduction cascade in the retina. Recent ocular imaging developments have further revealed the influence of sildenafil on ocular hemodynamics, particularly choroidal perfusion. Choroidal thickness is increased, and choroidal perfusion is also enhanced by autoregulatory mechanisms that are further dependent on age and microvascular abnormalities. Studies demonstrating high intraocular pressure via a "parallel pathway" from increased choroidal volume and blood flow to the ciliary body have challenged previous concepts. Another new observation is the effect of sildenafil on bipolar cells and cyclic-nucleotide gated channels. We discuss potential deleterious effects (central serous chorioretinopathy, glaucoma, ischemic optic neuropathy, and risks to recessive carriers of retinitis pigmentosa), potential beneficial effects (ameliorate choroidal ischemia, prevent thickening of Bruch membrane, and promote recovery of the ellipsoid zone) in macular degeneration, as well as potential drug interactions of sildenafil.

Unilateral acute anterior uveitis with macular edema following the use of sildenafil citrate in a patient with HLA-B27 positivity.

PURPOSE: To present a case of acute anterior uveitis with macular edema associated with sildenafil citrate use in an HLA-B27 positive patient. OBSERVATIONS: A 54-year-old Caucasian male presented at an ophthalmology tertiary center with complaint of pinkish discoloration, irritation, and photophobia in the left eye (OS). He noted that these symptoms appeared one day after using sildenafil for the first time to treat his erectile dysfunction. The patient had no significant ocular history besides refractive surgery in both eyes (OU) and his medical history was insignificant. Best-corrected visual acuity (BCVA) was 20/20 in the right eye (OD) and 20/25 in OS. Slit-lamp-examination (SLE) demonstrated trace cells and 1+ flare in the anterior chamber (AC) in OS and was nonrevealing in AC in OD. Spectral domain optical coherence tomography (SD-OCT) showed parafoveal subretinal hyperreflective deposits in OU. The patient was diagnosed with acute anterior uveitis (AAU) in the left eye and was placed on topical prednisolone acetate.At 2-week follow-up, the patient reported that his eye symptoms had improved since starting topical steroids but worsened again two days after he had used sildenafil for a second time. In OS, best-corrected visual acuity (BCVA) worsened to 20/40, and SLE revealed 1+ cells and 1+ flare in AC. SD-OCT revealed cystoid macular edema only in OS. Fluorescein angiography showed mild staining around the optic disc and significant macular leakage in OS and minimal macular leakage in OD. Uveitis evaluations revealed that the patient was human leukocyte antigen-27 (HLA-B27) positive. The patient was asked to remain off sildenafil and continue topical prednisolone acetate. At 3-month follow-up, BCVA improved to 20/20 in OS with no evidence of active inflammation. CONCLUSIONS AND IMPORTANCE: Sildenafil citrate use might be associated with new onset of intraocular inflammation in predisposed patients. Further studies are necessary to establish this relationship.

Second-derivative synchronous fluorimetry and time-programmed HPLC-fluorescence detection for simultaneous estimation of flibanserin and sitagliptin phosphate in synthetic mixtures and human plasma samples.

Diabetes Mellitus is directly related to female anaphrodesia. Female Viagra or Flibanserin (FLB), U.S. FDA approved in 2015, is specifically indicated for premenopausal Hypoactive Sexual Desire Disorder, HSDD, which is one of the primary consequences of Diabetes Mellitus. Simultaneous analysis of the concomitantly administered, FLB and oral antidiabetics, as Sitagliptin phosphate (STG), is a crucial demand to investigate mutual drug-drug interaction. The latter is responsible for uncontrolled glycaemia and higher risk of sudden hypoglycemia. Two simple, sensitive, economical and direct analytical methods, namely, Second-Derivative Synchronous Fluorimetric Spectroscopy, D2-SFS, and High Performance Liquid Chromatography with fluorimetric detection, HPLC-FD, are established for simultaneous determination of FLB and STG in their binary mixtures. First method relies on measuring D2-SFS spectra of both drugs, at Δλ = 25 nm, along linearity ranges of 0.05-1 µg/mL for both drugs. The second method is a chromatographic one with gradient elution of FLB and STG on RP-ZORBAX Eclipse C18 column (5 µm, 4.6 × 150 mm). Mobile phase; phosphate buffer: acetonitrile, pH 4.5, with a flow rate of 1 mL/min at room temperature has been used. Time programmed fluorimetric detection is optimized at λem = 305 nm for STG (0.0-5.9 min), at λem = 375 nm for FLB (6-9 min) after both excitation at λex = 257 nm, in the linear ranges of 1-40 µg/mL and 5-60 µg/mL for FLB and STG, respectively. Proposed methods have been validated according to ICH guidelines, then applied for simultaneous quantitation of FLB and STG in their laboratory-prepared mixtures and in spiked human plasma samples. Satisfactory Student's t-value and F-variance ratio have been obtained upon comparing the results of both methods.

The Weekend Drug; Recreational Use of Sildenafil Citrate and Concomitant Factors: A Cross-Sectional Study.

Background: Men who use erectile dysfunction medications for recreational purposes may be at increased risk of becoming psychologically dependent, which in turn could lead to psychogenic-based erectile dysfunction symptoms. Sildenafil has become one of the most commonly prescribed and abused drugs available today. Objectives: This study aimed to describe the utilization pattern and associated factors of sildenafil citrate among its users visiting community pharmacies in Gondar, Ethiopia. Methods: A facility-based cross-sectional study was conducted from March 20, 2017 to May 10, 2017, among male clients who visited community pharmacies in Gondar town, North West Ethiopia. A self-administered, structured questionnaire was used to collect data from Sildenafil users older than 18 years, that started using the drug (Sildenafil) for at least 6 months before the data collection period. A regression analysis was conducted to determine the association between study variables, and a P-value of <0.05 was considered to declare statistical significance. Results: A total of 65 men participated in the study. Of the total study participants, 33.8% were aged 25-34 years and about 40% of them had multiple sexual partners. The use of sildenafil for recreational purposes was 66.2% and was found to be higher than its use for medical purposes 33.8%. Use of the drug for <1-year duration (AOR = 34.086, 95% CI [2.90, 401.37]) and 2 years duration (AOR = 21.42: 95% CI [2.10, 218.82]) were significantly associated with its use for recreational purpose. Non-recreational use of sildenafil includes erectile problems associated with diabetes mellitus (27.1%), heart disease (9.2%), hyperlipidemia (4.2%), and relationship problems due to stress and poor communication (3.1%). Conclusion: Most men who use sildenafil citrate do so for recreational purposes, and use of sildenafil citrate for 2 years or less was associated with recreational use. There should be a collaborative effort among pharmacists, health professionals, and policymakers to improve the rational use of sildenafil.

Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord.

Multiple Sclerosis (MS) is a neuroinflammatory and chronic Central Nervous System (CNS) disease that affects millions of people worldwide. The search for more promising drugs for the treatment of MS has led to studies on Sildenafil, a phosphodiesterase type 5 Inhibitor (PDE5I) that has been shown to possess neuroprotective effects in the Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. We have previously shown that Sildenafil improves the clinical score of EAE mice via modulation of apoptotic pathways, but other signaling pathways were not previously covered. Therefore, the aim of the present study was to further investigate the effects of Sildenafil treatment on autophagy and nitrosative stress signaling pathways in EAE. 24 female C57BL/6 mice were divided into the following groups: (A) Control - received only water; (B) EAE - EAE untreated mice; (C) SILD - EAE mice treated with 25mg/kg of Sildenafil s.c. The results showed that EAE mice presented a pro-nitrosative profile characterized by high tissue nitrite levels, lowered levels of p-eNOS and high levels of iNOS. Furthermore, decreased levels of LC3, beclin-1 and ATG5, suggests impaired autophagy, and decreased levels of AMPK in the spinal cord were also detected in EAE mice. Surprisingly, treatment with Sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK. In conclusion, we propose that Sildenafil alleviates EAE by activating autophagy via the eNOS-NO-AMPK-mTOR-LC3-beclin1-ATG5 and eNOS-NO-AMPK-mTOR-CREB-BDNF pathways in the spinal cord.

Visual Side Effects Linked to Sildenafil Consumption: An Update.

Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician's direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes.