sildenafil-citrate and Tachycardia

Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review.. To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019.. All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism.. The authors independently extracted data and assessed the risk of bias of the trials.. Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low.. There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

Topics: Adrenergic Agents; Anemia, Sickle Cell; Diethylstilbestrol; Ephedrine; Estrogens, Non-Steroidal; Etilefrine; Humans; Male; Priapism; Randomized Controlled Trials as Topic; Sildenafil Citrate; Tachycardia; Vasoconstrictor Agents; Young Adult

Phosphodiesterases (PDEs) play a decisive role in cyclic nucleotide-mediated intracellular signaling. As PDEs are expressed in a variety of tissues, selectivity is a prerequisite for a therapeutically applicable PDE inhibitor. Sildenafil, vardenafil, and tadalafil are selective for PDE5, with vardenafil exhibiting the highest potency and minimal inhibition of other PDEs, with the exception of PDE6. Tadalafil is extremely selective for PDE5, but also potently inhibits PDE11, an enzyme with unknown physiological function. As PDE1 is expressed in the brain, myocardium, and vascular smooth muscle cells, nonselectivity with respect to this enzyme (selectivity: tadalafil>vardenafil>sildenafil) may result in vasodilation and tachycardia. Inhibition of PDE6 (selectivity: tadalafil>vardenafil congruent with sildenafil), which is expressed only in retina and functions in visual transduction, can transiently disturb vision. PDE5 inhibitors may also indirectly inhibit PDE3 by increasing cyclic guanosine monophospate levels, thereby elevating heart rate and vasodilation while inhibiting platelet aggregation.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Heart Rate; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Substrate Specificity; Sulfones; Tachycardia; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilation; Vision, Ocular

Methylmalonic acidemia or aciduria (MMA) is an inborn error of metabolism that results in the accumulation of methylmalonic acid in blood with an increased excretion in urine. MMA usually presents in early infancy and its effects vary from mild to life-threatening. The clinical symptoms mainly include vomiting, dehydration, hypotonia, developmental delay, and failure to thrive. An association between pulmonary arterial hypertension (PAH) and MMA has been rarely reported. In the present work, the authors report a 16-month boy, who was admitted to the Pediatric Department for cyanosis and fever. He had a family history of primary pulmonary hypertension in a sister. The echocardiography showed a mild pericardial effusion and PAH. The metabolic screening led to the diagnosis of MMA. The condition of the baby worsened rapidly- and he died a few days later. Physicians should be aware about this atypical presentation of the disease, which can be fatal if not diagnosed and managed promptly.

Topics: Amino Acid Metabolism, Inborn Errors; Cyanosis; Familial Primary Pulmonary Hypertension; Fatal Outcome; Fever; Humans; Infant; Male; Methylmalonic Acid; Renal Insufficiency; Sildenafil Citrate; Tachycardia; Vasodilator Agents

Sildenafil, a popular medication approved for the treatment of erectile dysfunction, is often misused. This study sought to describe the patterns of sildenafil calls to poison control centers in Texas during 1998-2004. Data on all sildenafil calls reported to the Texas Poison Center Network were analyzed. There were 628 sildenafil calls, 36% of which were human exposures and 44% were drug identifications. The number of calls increased during 1998-2003 but leveled off in 2004. The sildenafil exposure was isolated in 70% of the human exposure calls and involved other substances in 30% of the calls. Nonisolated exposures were more likely than isolated exposures to be intentional, involve males, occur in adults, and involve more serious problems as reflected by higher rates of health care facility treatment usage and more severe medical outcomes. The most frequently reported clinical effects were dizziness, tachycardia, erythema, and drowsiness. Most sildenafil calls were for human exposures or drug identification. The characteristics of human exposures such as the exposure reason and medical outcome were dependent on the presence of other substances.

Topics: Adolescent; Adult; Child; Child, Preschool; Dizziness; Erectile Dysfunction; Erythema; Humans; Male; Piperazines; Poison Control Centers; Purines; Retrospective Studies; Sildenafil Citrate; Sleep Stages; Sulfones; Tachycardia; Texas; Vasodilator Agents

Hepatic metabolism of sildenafil uses the same metabolic pathway as the calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme. The aim of this pilot study was to evaluate the potential interaction between sildenafil therapy and circulating levels of cyclosporine and tacrolimus in a group of steady-state renal transplant recipients with erectile dysfunction.. A prospective pilot study of sildenafil interactions was carried out in 9 stable male renal transplant recipients with severe erectile dysfunction (mean age 50 +/- 8 years, range 38-64). All patients were receiving therapy with calcineurin inhibitors (5 with cyclosporine and 4 with tacrolimus). Erectile dysfunction was evaluated by clinical history, physical examination, International Index of Erectile Function (IIEF) questionnaire and the nocturnal penile tumescence test (RigiScan). Each patient received a first dose of 50 mg of sildenafil, one hour before sexual activity and a second dose at 72 hours of 50 or 100 mg according to the clinical response to the first dose. We evaluated the efficacy and safety of sildenafil and the evolution of cyclosporine-tacrolimus levels. Cyclosporine and tacrolimus trough whole blood concentrations were determined in basal conditions (before starting sildenafil) and on days 1, 4 and 7 after sildenafil therapy.. Eighty-nine percent of patients (n = 8) required a complete 100 mg dose of sildenafil. There was a positive clinical response in two-thirds of cases (6 patients). In 5 patients (55%) sildenafil administration produced a complete response, in one patient the response was incomplete, and in the remaining 3 cases (33%) no clinical response was observed. Associated side effects included self-limited tachycardia in one patient and mild visual disturbances in another. Cyclosporine and tacrolimus levels remained stable in all patients. There were no significant differences in circulating levels of cyclosporine (basal 120 +/- 47; day 1: 116 +/- 55; day 4: 123 +/- 56 and day 7: 121 +/- 56 ng/ml p = NS) or tacrolimus (basal 11.6 +/- 1.3; day 1: 11.9 +/- 1.3; day 4: 11.1 +/- 1.0 and day 7: 11.8 +/- 0.9 ng/ml p = NS) over the study period.. Sildenafil therapy is safe and effective for the treatment of erectile dysfunction in renal transplant recipients. Recommended therapeutic doses of sildenafil did not modify cyclosporine and tacrolimus trough blood levels.

Topics: Adult; Calcineurin Inhibitors; Cyclosporine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Erectile Dysfunction; Graft Rejection; Humans; Immunosuppressive Agents; Inactivation, Metabolic; Kidney Transplantation; Male; Microsomes, Liver; Middle Aged; Pilot Projects; Piperazines; Purines; Safety; Sildenafil Citrate; Sulfones; Tachycardia; Tacrolimus; Treatment Outcome; Vasodilator Agents