sildenafil-citrate and Alcoholism

A fatal case of sildenafil citrate (Viagra) overdosage is presented. The deceased was a 56-year old male found dead at home, with a past history of diabetes mellitus, hypertension, chronic alcoholism, anxio-depressive disorders, and erectile dysfunction. The main autopsy findings were cardiomegaly (650 g) with dilated cardiomyopathy, diffuse coronary atherosclerosis with no sign of acute ischaemic disease, and extensive fibrosis of the myocardium, especially affecting the cardiac conducting tissue. As measured by HPLC/MS, sildenafil concentration in postrmortem blood (6.27 microg/mL) exceeded at least four times the highest therapeutic levels previously reported. The results are discussed in the light of the literature about the cardiovascular side effects of sildenafil, with special emphasis on the recently evidenced arrhythmogenic potential of the drug. This is the first report of a fatality caused by sildenafil overdosage.

Topics: Alcoholism; Autopsy; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Diabetes Complications; Drug Overdose; Fatal Outcome; Humans; Male; Mass Spectrometry; Middle Aged; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Abusive chronic alcohol consumption can cause metabolic and functional derangements in the heart and is a risk factor for development of non-ischemic cardiomyopathy. microRNA 214 (miR-214) is a molecular sensor of stress signals that negatively impacts cell survival. Considering cardioprotective and microRNA modulatory effects of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, we investigated the impact of chronic alcohol consumption on cardiac expression of miR-214 and its anti-apoptotic protein target, Bcl-2 and whether sildenafil attenuates such changes. Adult male FVB mice received unlimited access to either normal liquid diet (control), alcohol diet (35% daily calories intake), or alcohol + sildenafil (1 mg/kg/day, p.o.) for 14 weeks (n = 6-7/group). The alcohol-fed groups with or without sildenafil had increased total diet consumption and lower body weight as compared with controls. Echocardiography-assessed left ventricular function was unaltered by 14-week alcohol intake. Alcohol-fed group had 2.6-fold increase in miR-214 and significant decrease in Bcl-2 expression, along with enhanced phosphorylation of ERK1/2 and cleavage of PARP (marker of apoptotic DNA damage) in the heart. Co-ingestion with sildenafil blunted the alcohol-induced increase in miR-214, ERK1/2 phosphorylation, and maintained Bcl-2 and decreased PARP cleavage levels. In conclusion, chronic alcohol consumption triggers miR-214-mediated pro-apoptotic signaling in the heart, which was prevented by co-treatment with sildenafil. Thus, PDE5 inhibition may serve as a novel protective strategy against cardiac apoptosis due to chronic alcohol abuse.

Topics: Alcoholism; Animals; Apoptosis; Disease Models, Animal; Heart Diseases; Male; Mice; MicroRNAs; Myocytes, Cardiac; Phosphodiesterase 5 Inhibitors; Phosphorylation; Signal Transduction; Sildenafil Citrate; Up-Regulation

The substantial frequency of drug resistance in persons recently infected with HIV implies exposure among HIV-uninfected individuals to HIV-infected persons with drug-resistant virus. Although there is an increasing emphasis on understanding high-risk behavior among HIV-infected patients, little work has focused on those with drug-resistant virus.. We examined antiretroviral-treated patients with drug resistance in the Study of the Consequences of the Protease Inhibitor Era, a clinic-based cohort of HIV-infected adults. Sexual behavior was ascertained by self-administered questionnaire. Genotypic antiretroviral resistance testing was performed on isolates from participants with a plasma HIV RNA level > or =100 copies/mL.. Among 279 participants on antiretroviral therapy, 168 (60%) had genotypic resistance to at least 1 drug. In those with drug resistance, 27% of men who have sex with men (MSM) and 11% of heterosexual men and women reported at least 1 episode of unprotected penile-anal or penile-vaginal intercourse in the previous 4 months; 17% of MSM and 6% of heterosexual participants reported unprotected intercourse with an HIV-uninfected or status unknown partner. In a multivariable model of predictors of unprotected anal or vaginal intercourse with an HIV-uninfected or status unknown partner, there was strong evidence for an effect of younger age, depression, and sildenafil use and moderate evidence for frequent alcohol use.. Among HIV-infected patients with drug-resistant viremia, there is a substantial prevalence of high-risk sex with HIV-uninfected partners. The presence of definable risk factors for unsafe sex suggests a role for targeted rather than broad intervention, particularly when resources are limited.

Topics: Adult; Age Factors; Aged; Alcoholism; Anti-HIV Agents; Depression; Drug Resistance, Viral; Female; HIV; HIV Infections; Humans; Male; Middle Aged; Multivariate Analysis; Needle Sharing; Piperazines; Plasma; Purines; Risk-Taking; RNA, Viral; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Unsafe Sex