sildenafil-citrate and Hypotension

Episodes of excessive vasospasm are common in patients with Raynaud's phenomenon (RP). Pharmacological treatment may often result in side-effects such as hypotension, leading to discontinuation of treatment. Review of therapeutic interventions with regard to tendency towards hypotension was done in medical databases including PubMed, Scopus, and Medline to summarize the current state of the knowledge. Despite the episodes of blood pressure drops caused by hypotension, calcium channel blockers (CCB) have been widely used in RP as first-line treatment medication. The use of other CCB apart from nifedipine is controversial due to the variety of results in clinical trials. A clinical study comparing the efficacy and tolerability of losartan with nifedipine revealed a significant reduction in RP severity, frequency of episodes, and reported adverse effects. Application of oral sildenafil 100 mg/d as an add-on therapy increased microvascular blood flow in secondary RP, while being well-tolerated and with no withdrawal from the study. Topical vasodilators may be applied as an adjuvant therapy for patients with RP. Clinical studies approved 10% nifedipine cream and 10% nitroglycerine gel as an efficient RP therapy with side-effects comparable with placebo usage. Non-pharmacological interventions, such as cold avoidance, stress management, and smoking cessation are recommended in reducing episodes of RP. Calcium channel blockers, with a particular emphasis on nifedipine, in combination with non-pharmacological management seem to be the optimal way to treat the patients with a tendency to hypotension.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Humans; Hypotension; Losartan; Nifedipine; Nitroglycerin; Raynaud Disease; Sildenafil Citrate; Smoking Cessation; Stress, Psychological; Vasodilator Agents

Topics: Antihypertensive Agents; Contraindications; Coronary Disease; Drug Interactions; Drug Therapy, Combination; Erectile Dysfunction; Female; Humans; Hypertension, Pulmonary; Hypotension; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction occurs commonly in untreated and treated hypertensive patients, impairing adherence to treatment and quality of life. Furthermore, it is a marker for enhanced risk for cardiovascular disease. Phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, provide effective treatment of erectile dysfunction. They reduce blood pressure in healthy patients: sildenafil 100 mg, -3.7/-3.6 mm Hg; vardenafil 20 mg, -7.5/-8 mm Hg; and tadalafil 20 mg, -1.6/-0.8 mm Hg. Greater declines in blood pressure with a PDE5 inhibitor may be observed in treated and untreated hypertensive patients. The additive effect of PDE5 inhibitors with one or multiple antihypertensive drugs is modest. alpha(1)-Blockers, except tamsulosin, may result in larger declines in blood pressure and cause orthostatic hypotension. Thus, caution should be exercised by using the lowest doses of proportional, variant(1)-blockers and PDE5 inhibitors in combination. Nitrates in combination with PDE5 inhibitors cause a profound decline in blood pressure and are contraindicated.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Antihypertensive Agents; Blood Pressure; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypertension; Hypotension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vascular Resistance

Therapy of erectile dysfunction has been revolutionised in recent years, as specific pharmacological inhibitors of phosphodiesterase 5 (PDE5), such as sildenafil, tadalafil, or vardenafil, were shown to be highly effective in the treatment of erectile dysfunction. They dilate arterial smooth muscle cells of the corpora cavernosa, which express PDE5 abundantly, by inhibiting the breakdown of 3'5'-cyclic guanosine monophosphate. Despite theoretical concerns of a reduced myocardial tolerance to ischaemia or promoting cardiac arrhythmias, randomised trials and retrospective analyses do not support an increased cardiac risk with oral treatment. Therapeutic doses of PDE 5 inhibitors exhibit slight blood pressure lowering effects, and do not appear to compromise coronary blood flow in coronary artery disease. However, the combination of PDE5 inhibitors with any nitric oxide donor is absolutely contraindicated because of potentially life-threatening hypotension. Before prescribing medication for erectile dysfunction, any patient with cardiovascular disease should be evaluated for a potential risk of a cardiovascular event during sexual activity according to the Princeton Consensus Panel. When a stable cardiac condition can be achieved (low risk group), oral treatment for erectile dysfunction may be appropriate.

Topics: Administration, Oral; Apomorphine; Blood Pressure; Cardiovascular Diseases; Contraindications; Dopamine Agonists; Drug Interactions; Erectile Dysfunction; Humans; Hypotension; Male; Nitric Oxide Donors; Patient Selection; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Assessment; Sildenafil Citrate; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adrenergic alpha-Antagonists; Arteriosclerosis; Blood Pressure; Carbolines; Contraindications; Coronary Disease; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Interactions; Endothelium, Vascular; Erectile Dysfunction; Heart Rate; Humans; Hypotension; Imidazoles; Isosorbide Dinitrate; Male; Molecular Structure; Myocardial Infarction; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilation; Vasodilator Agents

Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. ED may also be an early sign of cardiovascular disease. The main risk factors for coronary heart disease (high LDL, smoking, hypertension, diabetes) and ED are the same. ED after the diagnosis of coronary artery disease or myocardial infarction is also common.. Cardiac and metabolic expenditures during sexual intercourse will vary depending on the type of sexual activity. When oxygen uptake was measured in men, an average metabolic expenditure during stimulation and orgasm of 2.5 metabolic equivalents (METs) was found for woman-on-top coitus, and of 3.3 METs for man-on-top coitus (range 2.0-5.4 METs). However, coital death is rare, encompassing only 0.6% of all sudden death cases. A retrospective case-crossover study has shown that although sexual activity can trigger the onset of myocardial infarction, the relative risk in the 2 h after sexual activity was low (2.5; 95% confidence interval [CI] 1.7-3.7). Sexual activity was a likely contributor to the onset of myocardial infarction only 0.9% of the time. Regular exercise appears to prevent triggering. It has to be cautioned that these reassuring data should not be extrapolated to patients taking sildenafil, if they perform at higher cardiac and metabolic expenditures during coitus. The hemodynamic changes associated with sexual activity may be far greater with an unfamiliar partner, in unfamiliar settings, and after excessive eating and drinking. The Princeton Consensus Table for estimation of cardiovascular risk during sexual intercourse gives a first orientation regarding the question which patients can perform sex safely and which subgroup needs further diagnosis and treatment. PHOSPHODIESTERASE-5 INHIBITORS FOR ED TREATMENT: The introduction of sildenafil has been a valuable contribution to the treatment of ED. Sildenafil acts as a selective inhibitor of cyclic guanosine monophosphate-(cGMP-)specific phosphodiesterase type 5 (PDE 5), resulting in smooth muscle relaxation, vasodilation, and enhanced penile erection. Reported cardiovascular side effects in healthy males are headache, flushing, and < 10% decreases in systolic and diastolic blood pressures. Significant hypotension can be found in patients who are concurrently taking nitrates. On the basis of the pharmacokinetic profile of sildenafil, the co-administration of a nitrate within the first 24 h is likely to produce a severe, potentially lifethreatening hypotensive response and is therefore contraindicated. The risk of precipitating a cardiotoxic, hypotensive, or hemorrhagic event secondary to combining sildenafil (a PDE 5 inhibitor) with specific PDE 3 inhibitors such as milrinone and enoximone or with nonspecific PDE inhibitors such as theophylline and pentoxifylline is unlikely. Sildenafil is pred. Sildenafil is safe in healthy subjects. In a postmarketing study on 6,527 males, no increase of cardiovascular events was found. However, in older males with coronary heart disease, the risk of sildenafil and the risk of physical exercise during sexual intercourse contribute both to fatal outcomes. Of 69 cases reported to the FDA, 46 patients might have had a cardiovascular event, and in twelve a possible interaction with nitrate use has been reported. Sildenafil is absolutely contraindicated in patients taking long-acting nitrates, those with severe aortic stenosis, and patients with hypertrophic obstructive cardiomyopathy (HOCM). No nitrates should be used within 24 h of sildenafil use. Caution is necessary in patients with a combination of antihypertensive medications, and in patients with cardiac insufficiency. A "pre-Viagra" treadmill test to assess for the presence of stress-induced ischemia can be helpful for both the patient and the physician. If the patient can achieve > or = 5 METs without demonstrating ischemia, the risk of ischemia during coitus is low.. If severe hypotension occurs, aggressive fluid resuscitation is the first step, followed by administration of vasoactive drugs and, if necessary, by intraaortic balloon counterpulsation. If unstable angina or myocardial infarctions occurs after the use of sildenafil, the patient is treated according to the guidelines, but without nitrates.. Sexual activity is a cornerstone of quality of life. However, giving the incidence of "occult" cardiovascular disease in patients with ED and the indications and contraindications of PDE 5 inhibitors in patients with cardiovascular diseases, all patients with ED must be evaluated by a cardiovascular specialist.

Topics: Coronary Disease; Drug Interactions; Erectile Dysfunction; Hemodynamics; Humans; Hypotension; Male; Myocardial Infarction; Piperazines; Purines; Risk Factors; Sexual Behavior; Sildenafil Citrate; Sulfones; Vasodilator Agents

Erectile dysfunction is a common problem affecting men. Sildenafil (Viagra) is the first oral medication approved for the treatment of erectile dysfunction. It has proven to be an effective option in the treatment of erectile dysfunction of different etiologies.

Topics: Clinical Trials as Topic; Contraindications; Drug Synergism; Erectile Dysfunction; Humans; Hypotension; Male; Nitrates; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

To characterize the safety of sildenafil in premature infants.. A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring.. Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases.. Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.. ClinicalTrials.gov Identifier: NCT01670136.

Topics: Humans; Hypotension; Infant, Extremely Premature; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Sildenafil Citrate

Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation.. This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test.. The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 µg/kg/min) or SIL (100 mg, single dose).. Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 ± 2.08 vs. 8.11 ± 1.81 cm/s, p = 0.002; SNP: 6.64 ± 1.51 vs. 7.72 ± 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis.. Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation.

Topics: Blood Pressure; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Hypotension; Male; Middle Aged; Nitroprusside; Piperazines; Preoperative Care; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasodilator Agents; Ventricular Function

The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood.. The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants.. We extracted information on sildenafil dosing and clinical characteristics from electronic health records of 348 neonatal ICUs from 1997 to 2013, and we predicted drug exposure using a population pharmacokinetic model.. We identified 232 infants receiving sildenafil at a median dose of 3.2 mg/kg/day (2.0, 6.0). The median steady-state area under the concentration-time curve over 24 hours (AUC24,SS) and maximum concentration of sildenafil (Cmax,SS,SIL) were 712 ng×hour/ml (401, 1561) and 129 ng/ml (69, 293), respectively. Systemic hypotension occurred in 9% of the cohort. In multivariable analysis, neither dosing nor exposure were associated with systemic hypotension: odds ratio=0.96 (95% confidence interval: 0.81, 1.14) for sildenafil dose; 0.87 (0.59, 1.28) for AUC24,SS; 1.19 (0.78, 1.82) for Cmax,SS,SIL.. We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil's safety profile in infants is warranted.

Topics: Administration, Oral; Cohort Studies; Female; Humans; Hypertension, Pulmonary; Hypotension; Infant; Infant, Newborn; Male; Multivariate Analysis; Phosphodiesterase 5 Inhibitors; Regression Analysis; Sildenafil Citrate

Infarto medular y de cuerpos vertebrales cervicales tras consumo de sildenafilo.

Topics: Angiography; Bradycardia; Cardiopulmonary Resuscitation; Cervical Vertebrae; Heart Arrest; Humans; Hypotension; Infarction; Male; Middle Aged; Paresis; Sildenafil Citrate; Spinal Cord; Spinal Cord Ischemia; Sympathetic Nervous System; Vasoconstriction

To compare the occurrence of hypotension following administration of intermittent intravenous (IV) and enteral sildenafil for treatment of pulmonary hypertension (PH) in infants. We hypothesized there may be more adverse effects associated with intermittent IV sildenafil compared with enteral sildenafil.. This was a retrospective matched-cohort study conducted in a tertiary care children's hospital. Patients were included if they were less than 1 year of age and received intermittent sildenafil for PH. Exclusion criteria consisted of concurrent extracorporeal membrane oxygenation during the initiation of sildenafil, the utilization of sildenafil as a one-time dose, continuation of home-dosing regimen, or inclusion in the other cohort. A total of 40 patients were matched 1:1 based on postmenstrual age and primary diagnosis.. There was no statistically significant difference in the primary outcome, as 30% (6/20) of patients receiving IV sildenafil required a hypotension intervention compared with 10% (2/20) in the enteral cohort (P = 0.24). The majority of interventions occurred within 24 hr of the initiation of sildenafil with 4/6 patients (67%) in the IV group and 2/2 patients (100%) in the enteral group, respectively. Baseline mean arterial pressure was significantly lower in the IV patients that required an intervention compared with those that did not (44 ± 6.3 vs. 65 ± 13.4 mmHg, P = 0.0024).. There were no statistically significant differences in safety outcomes between intermittent IV and enteral sildenafil in infants with PH. Hemodynamic parameters should be monitored closely upon sildenafil initiation. Limitations include the retrospective nature and small sample size. Pediatr Pulmonol. 2017;52:232-237. © 2016 Wiley Periodicals, Inc.

Topics: Administration, Intravenous; Administration, Oral; Case-Control Studies; Drug Administration Routes; Drug Administration Schedule; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Hypotension; Infant; Infusions, Intravenous; Male; Retrospective Studies; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents

Sildenafil, a phosphodiesterase-5 inhibitor, is a controversial treatment option for pulmonary arterial hypertension (PAH), a significant complication of bronchopulmonary dysplasia (BPD). The objective of this study was to evaluate the use of sildenafil in infants with PAH secondary to BPD. This was a retrospective review of medical records of all premature infants with PAH associated with BPD treated with sildenafil between January 2009 and May 2013 in a level 3 neonatal intensive care unit. The primary outcomes were clinical response (20 % decreases in respiratory support score or oxygen requirements) and echocardiographic response (20 % decrease in tricuspid regurgitation gradient or change of at least 1° of septal flattening). Twenty-three infants were included in the study. Significant echocardiographic and clinical responses were, respectively, observed in 71 and 35 % of cases. Most clinical responses were observed in the first 48 h of treatment, and the median time to an echocardiographic response was of 19 days. The median dose of sildenafil used was 4.4 mg/kg/day, with a median time to reach the maximum dose of 9 days. Transient hypotension was the primary reported side effect, and it was observed in 44 % of our study population. Sildenafil treatment in patients with PAH secondary to BPD was associated with an echocardiographic improvement in the majority of patients, whereas clinical improvement was observed in a minority of patients. Many infants presented with transient hypotension during the course of the treatment. Further prospective studies are required to better assess safety and efficacy of this treatment in this population.

Topics: Bronchopulmonary Dysplasia; Dose-Response Relationship, Drug; Echocardiography; Female; Humans; Hypertension, Pulmonary; Hypotension; Infant; Infant, Newborn; Intensive Care, Neonatal; Male; Oxygen; Phosphodiesterase 5 Inhibitors; Respiratory Rate; Retrospective Studies; Sildenafil Citrate; Treatment Outcome; Tricuspid Valve Insufficiency

We report significant hypotension and prerenal failure in an extremely preterm infant following two doses of oral sildenafil that warranted discontinuation of the drug and treatment with inotropes. Blood pressure and urine output normalized after 24 h of withdrawal of the oral drug. Sildenafil should be used cautiously in extremely preterm infants early in the neonatal course, where there is limited data on its efficacy and safety.

Topics: Acidosis, Lactic; Administration, Oral; Female; Humans; Hypotension; Infant, Extremely Premature; Infant, Newborn; Kidney; Persistent Fetal Circulation Syndrome; Sildenafil Citrate; Vasodilator Agents

We evaluated the effects of the highly selective phosphodiesterase type 5 inhibitor avanafil on electroretinogram and hemodynamics in dogs, and compared the effects with those of sildenafil.. Three experiments were performed in anesthetized dogs, including determination of the 1) influence on electroretinogram induced by a light adapted 30 Hz flicker stimulation, 2) direct hemodynamic changes and 3) potentiation of nitroglycerin induced hypotension. Avanafil was administered at doses that were pharmacologically equipotent to or higher than those of sildenafil for penile tumescence.. 1) Intraduodenal doses of avanafil did not influence the electroretinogram waveform. In contrast, sildenafil changed the waveform shape and significantly delayed time to the peak of the electroretinogram positive waveform (vs vehicle p <0.05). 2) Intravenous infusion of avanafil or sildenafil (1 to 300 μg/kg per minute) significantly decreased systemic blood pressure, total peripheral resistance and pulmonary arterial pressure (vs vehicle p <0.05). Administration of sildenafil but not avanafil significantly decreased the resistance of common carotid and vertebral arteries (vs vehicle p <0.05). 3) Intraduodenal doses of avanafil or sildenafil (0.1 and 1 mg/kg) potentiated the AUC of nitroglycerin induced hypotension. However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05).. Data suggest that avanafil has a favorable safety profile for erectile dysfunction, which is attributable to its high inhibitory selectivity for phosphodiesterase type 5 against type 6 (retina) and 1 (vessels, etc), respectively, and its short acting pharmacodynamic property.

Topics: Analysis of Variance; Animals; Area Under Curve; Dogs; Electroretinography; Erectile Dysfunction; Hemodynamics; Hypotension; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Retina; Signal Transduction; Sildenafil Citrate; Sulfones

Topics: Aged; Fatal Outcome; Humans; Hypotension; Kidney Failure, Chronic; Male; Piperazines; Purines; Pyrimidinones; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Atenolol; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Drugs, Chinese Herbal; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Hypotension; Male; Optic Nerve; Optic Neuropathy, Ischemic; Phosphodiesterase Inhibitors; Piperazines; Purines; Retinal Artery; Risk Factors; Sildenafil Citrate; Simvastatin; Sulfones; Vision, Low

The authors report one case of persistent pulmonary hypertension that had hypoxia although receiving treatment with high frequency oscillation, inotropic drugs, blood transfusion, and oral sildenafil for pulmonary vasodilatation. The patient developed hypotension after two doses of oral sildenafil and no response to high dose of inotropic drugs. So aerosolized iloprost was given via endotracheal tube and oxygen saturation improved within 10 minutes. Oxygen was weaned at 36 hours after treatment with this drug and no any side effect was found.

Topics: Female; High-Frequency Ventilation; Humans; Hypotension; Iloprost; Infant, Newborn; Intubation, Intratracheal; Persistent Fetal Circulation Syndrome; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Failure; Vasodilator Agents

Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP.. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration.. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Dogs; Drug Synergism; Heart Rate; Hypotension; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilation; Vasodilator Agents

Effects of ranolazine on isosorbide dinitrate- and on sildenafil-induced changes in mean arterial pressure and heart rate were assessed in conscious dogs. Dogs (n = 7) were chronically instrumented for measurements of mean arterial pressure and heart rate. Bolus intravenous injections of either isosorbide dinitrate (0.2 mg/kg) or sildenafil (0.5 mg/kg) caused biphasic changes in mean arterial pressure and heart rate: a transient (approximately 20 s) decrease in mean arterial pressure and an increase in heart rate, followed by prolonged (10-15 min) decreases in mean arterial pressure by 11 +/- 1.6 and 11 +/- 2.2 mm Hg, respectively. Infusion of ranolazine alone (plasma concentrations = 4 or 8 microM) for 10 min did not significantly affect mean arterial pressure and heart rate. The transient hypotension and tachycardia caused by isosorbide dinitrate were not altered by ranolazine. The sildenafil-induced transient tachycardia (Delta change: 114 +/- 10 beats/min) was significantly (P < 0.05) blunted by either 4 (Delta change: 71 +/- 8 beats/min) or 8 (Delta change: 66 +/- 9 beats/min) microM ranolazine. However, the sildenafil-induced transient decrease in mean arterial pressure was not altered by ranolazine. During ranolazine infusion (4-5 or 8-10 microM), isosorbide dinitrate and sildenafil caused prolonged decreases in mean arterial pressure. These results indicate that except for a blunting of the transient tachycardia caused by sildenafil, ranolazine at concentrations up to 10 microM does not alter changes in mean arterial pressure and heart rate induced by either isosorbide dinitrate or sildenafil in conscious dogs.

Topics: Acetanilides; Angina Pectoris; Animals; Blood Pressure; Dogs; Enzyme Inhibitors; Heart Rate; Hypotension; Injections, Intravenous; Isosorbide Dinitrate; Male; Piperazines; Purines; Ranolazine; Sildenafil Citrate; Stimulation, Chemical; Sulfones; Vasodilator Agents

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Antihypertensive Agents; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypertension; Hypotension; Nitroprusside; Piperazines; Purines; Sildenafil Citrate; Sulfones

Sildenafil citrate is the first FDA-approved oral agent for male erectile dysfunction. Common adverse effects include flushing, headache, and dyspepsia, although more serious side effects have been reported. Because of its specific therapeutic indication, sildenafil toxicity has been limited almost exclusively to adults. We report a symptomatic case of pediatric sildenafil ingestion.. A 2-year-old male ingested 75 mg of sildenafil citrate (Viagra) 2 hours prior to arrival at an emergency room. Ipecac syrup had been given at home with one episode of vomiting. Activated charcoal was considered but withheld due to the delayed presentation to the hospital. The patient was observed in the hospital for 17.5 hours. Observed clinical effects included facial flushing, transient penile engorgement, bilateral rhonchi, and diarrhea. No significant cardiovascular effects were seen. A bronchodilator was given with resolution of rhonchi. No other specific interventions were required. One day after discharge, the patient had one additional bout of diarrhea and complained of pain in the penile region for one day. Two weeks after the exposure, the patient's mother denied any unusual symptoms.. Pediatric ingestion of sildenafil may result in mild symptoms including persistent flushing and penile engorgement with associated pain. Penile pain may persist even after resolution of the erection. It is questionable whether the respiratory symptoms and diarrhea were related since neither has been described following sildenafil exposure. Significant cardiovascular symptoms were not seen. Early administration of ipecac syrup did not prevent symptoms from developing.

Topics: Bronchodilator Agents; Child, Preschool; Diarrhea; Emetics; Flushing; Humans; Hypotension; Ipecac; Male; Piperazines; Poisoning; Priapism; Purines; Respiratory Sounds; Sildenafil Citrate; Sulfones

Topics: Humans; Hypotension; Ischemic Attack, Transient; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Stroke; Sulfones; Vasodilator Agents

We investigated whether sildenafil citrate (Viagra) may reduce the dose of nitrovasodilators to induce deliberate hypotension. Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. Sodium nitroprusside (SNP; 1-16 microg. kg(-1). min(-1)) or nitroglycerin (NTG; 2-32 microg. kg(-1). min(-1)) was IV given to induce hypotension. The study consisted of two occasions, in a random order, in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg. kg(-1). h(-1)) and the other without to serve as a control. Hemodynamic variables were continuously monitored. Plasma cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay. Both SNP and NTG produced dose-dependent decreases in mean arterial blood pressure without affecting the heart rate in the presence as well as in the absence of sildenafil. Systemic vascular resistance index and mean pulmonary arterial pressure were also decreased. The magnitude of mean arterial blood pressure and systemic vascular resistance index reductions caused by SNP was augmented by sildenafil, whereas that caused by NTG was not affected. Neither SNP nor NTG alone altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP but not affected by NTG. These results indicate that sildenafil may reduce the dose of SNP in producing deliberate hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented accumulation of cGMP.. Sildenafil may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cyclic GMP; Dogs; Drug Synergism; Female; Hypotension; Male; Nitroglycerin; Nitroprusside; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Coronary Circulation; Drug Synergism; Humans; Hypotension; Isosorbide Dinitrate; Male; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. Because of the phosphodiesterase-5 inhibitor-induced increases of cyclic GMP in the vasculature, vasodilation in various vascular beds is induced, which in combination with various nitrovasodilators (e.g., when used simultaneously for the treatment of coronary artery disease), may lead to excessive hypotension. Thus nitrovasodilators are contraindicated when sildenafil may be used and reports of a number of accidents have recently been published. We therefore studied the acute interactions of glyceryl trinitrate (GTN), pentaerythritol tetranitrate (PETN), and isosorbide dinitrate (ISDN) with sildenafil in six chronically instrumented conscious dogs for each nitrate to assess the magnitude of blood pressure drops (and compensatory increases in heart rate) during a 24-h nitrate administration (infusion into the pulmonary artery). Sildenafil (3 mg/kg) was given orally (after a 24-h fast) 30 min after start of nitrate infusion. GTN, PETN, or ISDN (which follow different steps of metabolic conversion to nitric oxide) were applied at submaximal dosages leading to 90% of maximal coronary artery dilation at 1.5 microg/kg per min, 0.75 microg/kg per min, or 6 microg/kg per min, respectively. During GTN infusion sildenafil caused a maximum drop in mean blood pressure of 21 +/- 3 mm Hg (rise in heart rate from 117.0 +/- 7.2 to 126.0 +/- 6 .0/min) and during ISDN infusion of 18 +/- 3 mm Hg (rise in heart rate from 115.0 +/- 7.0 to 125 +/- 6/min), which was significantly less (p < 0.01) during PETN (only 6 +/- 1 mm Hg with a rise in heart rate from 107.0 +/- 5.0 to 122.0 +/- 7.0/min). When sildenafil is used during exposure to nitrates (e.g., in coronary artery disease), the PETN-induced drop in blood pressure at equi-effective dosages (with regard to coronary dilation) is substantially smaller compared with that of GTN or ISDN, which is probably because of lesser potentiation of phosphodiesterase-5 inhibitor-induced effects in the arteriolar bed, thus minimizing critical drops in blood pressure.

Topics: Animals; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Drug Synergism; Female; Free Radicals; Heart Rate; Hypotension; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Drug Synergism; Humans; Hypotension; Male; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Aged; Cardiac Catheterization; Cardiovascular Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Diltiazem; Drug Interactions; Erectile Dysfunction; Humans; Hypotension; Male; Mixed Function Oxygenases; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Diltiazem; Drug Interactions; Humans; Hypotension; Mixed Function Oxygenases; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Antihypertensive Agents; Drug Interactions; Humans; Hypotension; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Cardiovascular Diseases; Contraindications; Erectile Dysfunction; Humans; Hypotension; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Topics: Drug Administration Schedule; Electrocardiography; Erectile Dysfunction; Humans; Hypotension; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Polycystic Kidney Diseases; Purines; Renal Dialysis; Sildenafil Citrate; Sulfones

Topics: Aged; Angina Pectoris; Coronary Angiography; Diltiazem; Humans; Hypotension; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Aged; Drug Therapy, Combination; Humans; Hypotension; Male; Myocardial Infarction; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

A 55-year-old Japanese man was hospitalized for palpitations and severe chest oppression one hour after he ingested about 1500 ml of beer and sildenafil (Viagra) 50 mg. At 43 years of age, he had been diagnosed with intermittent WPW syndrome following a paroxysmal supraventricular tachycardia (PSVT) attack. He took a 1 mg tablet of doxazosin daily for mild hypertension. On admission, his blood pressure was 90/54 mmHg and his heart beat was weak and irregular with a rate of about 220/min. Since atrial fibrillation (Af) was diagnosed on an electrocardiogram (minimum RR interval; 0.22 seconds), direct current shock was performed with 100 joules and 150 joules but conversion to sinus rhythm failed. Sinus rhythm returned spontaneously from Af four hours after taking sildenafil. Since blood pressure was 50/17 mmHg despite the return to sinus rhythm, blood pressure was maintained by dopamine for twelve hours after sinus rhythm returned. The patient underwent catheter ablation for curative therapy and thereafter has not had any further episodes of tachycardia.

Topics: Atrial Fibrillation; Electrocardiography; Humans; Hypotension; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Wolff-Parkinson-White Syndrome

Topics: Administration, Oral; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Erectile Dysfunction; Fees, Pharmaceutical; Humans; Hypotension; Male; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones

Topics: Cyclic GMP; Drug Interactions; Erectile Dysfunction; Female; Humans; Hypotension; Male; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cyclic GMP; Drug Interactions; Erectile Dysfunction; Humans; Hypotension; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Topics: Chest Pain; Contraindications; Dental Care; Drug Interactions; Erectile Dysfunction; Humans; Hypotension; Male; Medical History Taking; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Pfizer, Inc., manufacturer of Viagra (sildenafil), is warning patients that Viagra is contraindicated with nitrate inhalers (poppers). Nitrates in any form or nitric oxide donors can potentially cause hypotension. Pfizer also recommends that patients using protease inhibitors, particularly ritonavir, use a lower dose of Viagra (25 mg) because they interfere with the elimination of Viagra. This interaction does not pose a significant risk to the patient.

Topics: Amyl Nitrite; Cytochrome P-450 Enzyme System; Drug Interactions; Enzyme Inhibitors; HIV Protease Inhibitors; Humans; Hypotension; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents