Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-anginal effects of KB-944 (Fostedil), a new calcium ion antagonist with a half life of approximately 23-28 hr, were evaluated in 20 patients with exertional angina pectoris in a placebo-controlled single-blind dose titration trial. Ambulatory monitoring and multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and after two 2-weekly periods of KB-944 therapy. The mean (+/- SEM) exercise time to the development of angina on treadmill walking increased from 6.9 +/- 0.4 min on placebo to 9.4 +/- 0.5 min on KB-944 100 mg/day (P less than 0.001) and 9.7 +/- 0.8 min on KB-944 200 mg/day (P less than 0.001 vs placebo and not significant vs KB-944 100 mg/day). The time to the development of 1 mm ST-segment depression of 5.3 +/- 0.4 min on placebo increased to 6.5 +/- 0.5 and 6.6 +/- 0.5 min on KB-944 100 and 200 mg/day, respectively (P less than 0.01 vs placebo). The heart rate at rest of 77 +/- 3 beats/min on placebo was reduced to 68 +/- 3 beats/min on KB-944 100 mg/day (P less than 0.001) and 71 +/- 2 beats/min on KB-944 200 mg/day (P less than 0.01). The maximal heart rate and the rate-pressure product were not altered by KB-944 therapy. One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn. Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day. One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day. The 24-hr ambulatory monitoring data confirmed the findings of exercise testing. KB-944 (Fostedil) in a dose of 100 mg once daily was well tolerated as compared to KB-944 200 mg once daily and both the doses were equally effective. The drug merits further evaluation for the treatment of exertional angina pectoris.
Int J Cardiol 1985 Nov
PMID:Ambulatory monitoring and exercise testing in the evaluation of a new long-acting calcium ion antagonist KB-944 (Fostedil) for the treatment of exertional angina pectoris. 390 75

The present study identified factors that distinguish early responders (i.e., requested medical assistance < 60 minutes after the onset of acute myocardial infarction [AMI] symptoms) from late responders (i.e., request made > or = 60 minutes after symptom onset). A questionnaire developed to assess demographic characteristics, contextual factors, antecedents to symptom onset, and behavioral, affective, and cognitive responses was administered in the hospital to 501 patients with documented AMI. Patients who believed that their symptoms were cardiac in nature were more likely to be early responders, whereas patients who attributed their symptoms to indigestion, muscle pain, fatigue, or another cause responded later (p < 0.0009). Early responders believed their symptoms to be more serious (p < 0.0001), felt more comfortable seeking medical assistance (p < 0.0001), were more anxious or upset when they first noticed symptoms (p = 0.0118), and perceived that they had less control of their symptoms (p < 0.0001) than late responders. A stepwise multiple regression analysis further suggested that unmarried patients responded significantly later than married patients, and patients who first experienced their symptoms at work responded significantly later than those who first experienced their symptoms outside of the home but not at work. These results suggest that situational and psychological variables are important determinants of lengthy decision delays in responding to symptoms of AMI.
Am J Cardiol 1995 May 15
PMID:Distinguishing between early and late responders to symptoms of acute myocardial infarction. 774 81

Clinical experience with fluvastatin in > 1,800 North American patients treated for an average of 61 weeks has shown it to be safe and well tolerated. Frequencies of transaminase and creatine kinase elevations compare favorably with those observed during long-term administration of other 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Further, whereas frank rhabdomyolysis has been encountered with treatment with all other HMG-CoA reductase inhibitors, this syndrome has not been observed to date with fluvastatin in studies here or abroad; a single case of myopathy, which was probably related to physical exertion, was reported in a patient receiving fluvastatin. Although dyspepsia was observed more commonly in fluvastatin patients the incidence, along with that of other adverse events (e.g., headache), and the number of treatment discontinuations proved statistically indistinguishable from those of placebo controls. Whether the favorable safety profile of fluvastatin is related to this synthetic agent's unique biopharmaceutical profile is a matter of ongoing long-term inquiry.
Am J Cardiol 1994 May 26
PMID:Updated clinical safety experience with fluvastatin. 819 19

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)
Am J Cardiol 1999 Mar 04
PMID:Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. 1007 39

Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oral sildenafil significantly improves erectile function and is well tolerated in patients with erectile dysfunction and ischemic heart disease who are not taking nitrate therapy.
Am J Cardiol 1999 Mar 04
PMID:Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. 1007 40

This study explores gender differences in symptom presentation associated with coronary heart disease (CHD). In this prospective study, nurse data collectors directly observed 550 patients as they presented to the Emergency Department (ED) of Yale-New Haven Hospital. The final sample included 217 patients (41% women) diagnosed with CHD (acute coronary ischemia or myocardial infarction). Chest pain was the most frequently reported symptom in women (70%) and men (71%). Unadjusted analyses revealed that women were more likely than men to present with midback pain (odds ratio [OR] 9.61, 95% confidence interval [CI] 2.10 to 44.11, p = 0.001), nausea and/or vomiting (OR 2.29, 95% CI 1.19 to 4.42, p = 0.012), dyspnea (OR 1.82, 95% CI 1.05 to 3.16, p = 0.032), palpitations (OR 3.42, 95% CI 1.02 to 11.47, p = 0.036), and indigestion (OR 2.13, 95% CI 1.03 to 4.44, p = 0.040). After adjustment for age and diabetes, women were more likely to present with nausea and/or vomiting (OR 2.43, 95% CI 1.23 to 4.79, p = 0.011) and indigestion (OR 2.13, 95% CI 1.10 to 4.53, p = 0.048). Women (30%) and men (29%) were equally likely to present without chest pain, and dyspnea was the most common non-chest pain symptom. In the subgroup of patients without chest pain, unadjusted analyses revealed that women were more likely to report nausea and/or vomiting compared with men (OR 4.40, 95% CI 1.30 to 14.84, p = 0.013). Although we found some significant gender differences in non-chest pain symptoms, we conclude that there were more similarities than differences in symptoms in women and men presenting to the ED with symptoms suggestive of CHD who were later diagnosed with CHD.
Am J Cardiol 1999 Aug 15
PMID:Gender differences in symptom presentation associated with coronary heart disease. 1046 75

Advances in molecular biology and protein chemistry, along with increasing understanding of the mechanisms of penile erection, have spurred development of pharmacologic approaches to the treatment of erectile dysfunction (ED). The next generation of oral agents includes tadalafil, a potent, highly selective phosphodiesterase 5 inhibitor. In vitro studies have shown that tadalafil enhances relaxation of trabecular smooth muscle, and clinical trials have supported its efficacy and tolerability in a broad population of men with ED. The effect of tadalafil in enhancing the erectile response to sexual stimulation is relatively rapid in onset and lasts for >or=24 hours. The ability of patients with ED treated with tadalafil to achieve improved erectile function is demonstrated by significantly increased subjective measures of penetration ability, successful intercourse, and sexual satisfaction. Partners have expressed similar or higher levels of satisfaction with the results of treatment. Men with ED of psychogenic, organic, or mixed etiology and in a range from mild to severe have experienced significant improvment with tadalafil treatment. Response to treatment in men with diabetes has been robust and not affected by disease severity. Tadalafil has been well tolerated. Adverse events have generally been mild or moderate and have abated with continued treatment. Headache and dyspepsia have been most frequently reported. Changes in color vision have been rare (<0.1%) with tadalafil across all clinical trials. Tadalafil appears to be a safe and effective treatment for men with ED.
Am J Cardiol 2003 Nov 06
PMID:Efficacy and tolerability of tadalafil, a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction. 1460 20

This was a double-blind, placebo-controlled, flexible-dose study of the efficacy and safety of sildenafil in men with erectile dysfunction (ED) and clinically stable coronary artery disease (CAD). Patients were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function (IIEF). Secondary outcomes included the other IIEF questions and functional domains, the Life Satisfaction Checklist, the Erectile Dysfunction Inventory of Treatment Satisfaction, 2 global efficacy assessment questions, and intercourse success rate. By week 12, sildenafil-treated patients (n = 70) showed significant improvements on questions 3 and 4 compared with placebo-treated patients (n = 72; p <0.01). Larger percentages of sildenafil-treated patients reported improved erections (64%) and improved intercourse (65%) compared with placebo-treated patients (21% and 19%, respectively). Sildenafil-treated patients were highly satisfied with treatment and their sexual life compared with placebo-treated patients. Forty-seven percent of sildenafil- and 32% of placebo-treated patients experienced adverse events, including transient headache, hypertension, flushing, and dyspepsia. There were no serious drug-related cardiovascular effects. Thus, sildenafil is an effective and well-tolerated treatment for ED in men with CAD. Sildenafil was not associated with additional safety risks in this patient population.
Am J Cardiol 2004 Jan 15
PMID:Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease. 1471 38

The mechanism of action of the phosphodiesterase type 5 (PDE5) inhibitors (i.e., sildenafil, tadalafil, and vardenafil) involves inhibition of the PDE5 isoenzyme located in penile vascular smooth muscle cells. Sexual stimulation triggers the release of nitric oxide (NO), stimulating the release of guanylyl cyclase, leading to an increase in intracellular cyclic guanosine monophosphate (cGMP) concentrations, a decrease in intracellular calcium, and ultimately relaxation of the vascular smooth muscle in the corpus cavernosum and penile erection. The PDE5 inhibitors have no effect on the penis in the absence of sexual stimulation. Although the various PDE5 inhibitors differ with respect to selectivity and pharmacokinetic profiles, efficacy and safety of these agents are comparable in broad populations of men with erectile dysfunction (ED), including those with diabetes or those taking multiple antihypertensive agents. The most frequently reported adverse events of the PDE5 inhibitors are related to their mild vasodilatory effects and include headache, flushing, dyspepsia, and nasal congestion or rhinitis. Side effects are generally reversible and tend to diminish during continued treatment. Differences in pharmacokinetic properties among the PDE5 inhibitors include the fact that sildenafil and vardenafil have a shorter duration of action (approximately 4 h) compared with the longer period of responsiveness observed with tadalafil (up to 36 h). In addition, in the presence of high-fat food, absorption of sildenafil and vardenafil may be delayed; however, the rate and extent of tadalafil absorption are unaffected by high-fat food.
Clin Cardiol 2004 Apr
PMID:Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profiles. 1511 91

Niacin or nicotinic acid is a soluble vitamin with hypolipidemic properties. Niacin reduces triglycerides (20 50%), LDL-c (5-25%), and raises HDL-c (15-35%). The Coronary Drug Project study showed that the use of niacin was associated with reduction on coronary events and total mortality, and more recently it has been demonstrated that niacin combined with other hypolipidemic drugs can attenuate the progression of coronary atherosclerosis. Niacin appears to reduce the mobilization of free fatty acids from the adipocytes, acting on specific receptors, diminishing the liver formation of triglyceride-rich lipoproteins. There are two forms of niacin, one of rapid absorption (crystalline), more commonly associated with flushing, and another of extended release, recently reported to be better tolerated. The use of niacin can be associated with dyspepsia, increased plasma levels of liver enzymes and also with a modest elevation in glucose and uric acid plasma levels, at least using the extended-release preparation up to 2 g/d.
Arq Bras Cardiol 2005 Oct
PMID:[Pharmacology of niacin or nicotinic acid]. 1640 Mar 92


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