Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemodynamic and antiischemic effects of a 150-mg single oral dose of the PDE inhibitor enoximone were correlated with the plasma levels of enoximone and its sulfoxide metabolite. Twenty-one patients with angiographically documented coronary artery disease were investigated by exercise testing 1 and 2 hours after drug administration. The control group consisted of 15 patients with proven coronary artery disease and stable reproducible angina pectoris on exercise. The enoximone group included 14 responders with therapeutic plasma concentrations 2 hours after drug intake and significantly reduced mean pulmonary artery pressures on exercise (from 42.4 +/- 8.6 to 30.9 +/- 11.2 mmHg, p less than 0.05). Compared to basal exercise values, responders showed a reduced ST-segment depression by 1 hour after drug intake (2.1 +/- 1.2 vs. 1.3 +/- 3 mm, p less than 0.05) and minimal values after 2 hours (0.9 +/- 1.0 mm, p less than 0.01) at comparable workloads. There were no significant changes in heart rate, blood pressure, cardiac output, and systemic vascular resistance. No significant improvement in the hemodynamic parameters and ST-segment depression was found in nonresponders with plasma concentrations below 100 ng/ml and 500 mg/ml for enoximone and its metabolite, respectively. In summary, oral administration of enoximone in patients with coronary artery disease led to favorable acute hemodynamic and antiischemic effects at sufficiently high plasma levels of enoximone and its sulfoxide metabolite.
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PMID:Antiischemic and hemodynamic effects of an oral single dose of 150 mg of the phosphodiesterase inhibitor enoximone in patients with coronary artery disease--relation to plasma concentration. 183 89

Positive inotropy requires a rise in myocardial oxygen consumption (MVO2); as far as PDE-III-inhibitors' beneficial hemodynamic effects, increases in contractility are controversial, in part probably because accurate proving is rather tedious. The clinician, however, requires a clear concept of whether or not enoximone (EN), for example, carries the risk of myocardial ischemia when used in patients with coronary artery disease. Using the analysis of pressure-volume relations, we recently established contractility-increasing as a partial effect of EN. There are indications suggesting that the inotropy-induced added increase in MVO2 of the PDE-III-inhibitor drugs could be compensated for by the simultaneous vasodilation and changes in compliance, so that as a net effect an unchanged MVO2 might result. Since, on the other hand, PDE-III-inhibitor drugs have been said to generate antiischemic properties, further clinical investigations with EN clearly seemed indicated and they are the subject of the present report: In five patient groups with stabile angina (AP) studied the following parameters and methods, respectively, were used for the evaluation of EN-induced changes of the anginal threshold: exercise, using pacing and ergometry; PA- and PC-pressure measurements; MVO2, indirectly assessed; hemodynamic profile and regional wall motion as assessed in the immediate post pacing phase; ST- T-segment evaluation; thalium-201 perfusion scintigraphy; myocardial perfusion, indirectly assessed. Lack of EN-induced AP (ischemia) and an increased AP threshold indicated that the drug can be used safety in patients with heart failure, including that due to coronary artery disease.
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PMID:[Effects of the phosphodiesterase III inhibitor in ischemic heart disease]. 192 97

We investigated the reason why butylidenephthalide (Bdph) can have an antianginal effect without changing blood pressure in conscious rats. Isolated dog coronary artery (CA), femoral vein (FV), femoral artery (FA), and mesenteric artery (MA) were used to evaluate the relaxant effects of Bdph. Bdph concentration-dependently relaxed isolated CA, FV, FA, and MA precontracted by KCl (60 mM) and phenylephrine (phe, 5 microM) with the exception that CA was precontracted by prostaglandin F 2 alpha (PGF 2 alpha, 2 microM) instead of phe. The potency order of Bdph to these blood vessels was FV > CA > FA > or = MA. Bdph also concentration-dependently and non-competitively inhibited cumulative KCl (5 - 120 mM)- and phe (0.1 - 100 microM)-induced contractions in normal, and inhibited cumulative Ca 2+-induced contractions in depolarized blood vessels. The potency order of Bdph to these blood vessels was FV congruent with CA > FA congruent with MA. Bdph (0.02 - 0.04 mM) concentration-dependently and leftward-shifted the log concentration-response curves in parallel and significantly increased the pD 2 value of forskolin, but not nitroprusside in FV. Bdph (0.1 mM) did both in CA. Bdph (0.225 - 0.45 mM) did the opposite to that of nitroprusside, but not forskolin, in FA. Bdph (0.45 - 0.9 mM) did neither in MA. Bdph (0.1 - 1 mM) significantly inhibited cAMP- but not cGMP-PDE activities in these four blood vessels, suggesting that Bdph more selectively inhibited the former in these tissues. The above results suggest that the higher potencies of Bdph on FV and CA than on FA and MA, may be interpreted as the reason why Bdph is useful in the treatment of angina pectoris without changing blood pressure, after Bdph administration in vivo, because the venoreturn may be reduced and the coronary flow may be increased without affecting the arterioles, such as MA, the main determinant of blood pressure. Abbreviations. Bdph:butylidenephthalide Phe:phenylephrine PGF 2alpha :prostaglandin F 2alpha CA:coronary artery FV:femoral vein FA:femoral artery MA:mesenteric artery cAMP:adenosine 3',5'-cyclic monophosphate cGMP:guanosine 3',5'-cyclic monophosphate PDE:phosphodiesterase
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PMID:Relaxant effects of butylidenephthalide in isolated dog blood vessels. 1245 91

Cardiovascular diseases like hypertension, hyperlipidemia, diabetes mellitus and obesity are the important predictors of erectile dysfunction (ED). Endothelial dysfunction is proposed to be the underlying cause of ED, just like coronary artery disease. Sildenafil was originally developed to treat angina pectoris but later on was recognized as novel treatment option for impotence. To date, sildenafil has been the most extensively studied PDE (phosphodiesterase)-5 inhibitor. Currently two more PDE-5 inhibitors, tadalafil and vardenafil, are under study. Newer compounds have certain advantages over sildenafil, including greater selectivity for PDE-5 compared with other isoenzymes, absence of effect of food on absorption, faster onset and longer duration of action. PDE-5 inhibitors are emerging as novel therapeutic tools with a potential to protect or enhance endothelial function in humans and to selectively improve regional blood flow. The FDA has recently approved a reformulation of sildenafil for the treatment of pulmonary arterial hypertension. Raynaud's phenomenon, respiratory disorders with ventilation/ perfusion mismatch, congestive cardiac failure, hypertension and stroke are the other conditions in which PDE-5 inhibitors are being tried. It is hoped that this group of drugs will soon emerge as a novel weapon in the armamentarium against various cardiovascular and pulmonary diseases.
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PMID:Novel phosphodiesterase-5 inhibitors: current indications and future directions. 1817 38

Sexual activity corresponds to light to moderate physical exercise and entails no significant risk to the majority of patients with cardiovascular disease. In patients suffering from severe angina or chronic heart failure, however, sexual activity might trigger coital angina or cardiac decompensation necessitating hospitalization. Nevertheless, even for patients with coronary artery disease the absolute risk of having a heart attack or fatal event during sexual activity is extremely low. Due to systemic atherosclerosis and concomitant endothelial dysfunction the prevalence of sexual dysfunction is higher in patients with cardiovascular disease as compared to the general population. PDE-5 inhibitors can be safely used by many patients suffering from both, cardiovascular disease and sexual dysfunction as long as no concomitant medication with nitrates exists. The concomitant use of PDE-5 inhibitors and nitrates is strictly contraindicated because of the risk of life-threatening hypotension. It is therefore of utmost importance to ask patients presenting with coital angina about PDE-5 inhibitor intake before the administration of nitrate-based anti-ischemic therapies. The recommendations of the Princeton Consensus Conference provide a useful framework for risk stratification and counseling of patients with cardiovascular disease regarding sexual activity.
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PMID:[Cardiovascular disease and sexuality]. 2023 42

Coronary artery disease (CAD) and erectile dysfunction (ED) frequently coexist. The introduction of phosphodiesterase type-5 (PDE-5) inhibitors has revolutionized medical management of organic ED; however, in patients with angina pectoris, a common symptom of CAD, coadministration of PDE-5 inhibitors and nitrates has been implicated in CAD-related deaths following sexual activity. The mechanism of action of PDE-5 inhibitors results in a potential cumulative drop in blood pressure (BP); thus, these agents are contraindicated in patients receiving nitrates. Beta-blockers and calcium channel antagonists are considered the mainstays of antianginal therapy, but may not be tolerated by all patients. Ranolazine is an antianginal agent that produces minimal reductions in heart rate and BP. Here we report three cases of men with CAD, chronic angina, and concomitant ED. We describe our treatment approach in these patients, using ranolazine as a potential substitute to nitrate therapy.
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PMID:Switching from nitrate therapy to ranolazine in patients with coronary artery disease receiving phosphodiesterase type-5 inhibitors for erectile dysfunction. 2545 6

Endothelial dysfunction precedes the clinical stage of atherosclerotic disease and is recognized as an additional risk factor when detecting symptomatic patients. Endothelial function is largely mediated by nitric oxide, and this vasodilatory mechanism is also responsible for the venous and arterial dilatation required to obtain and maintain an erection. The physiological effects and clinical aspects of sexual function have been extensively studied and reported in patients who have angina or who have experienced a myocardial infarction and in those who have undergone coronary artery bypass graft surgery or heart transplant. The relationship between erectile dysfunction (ED) and the risk factors for coronary heart disease was noted in the Massachusetts Male Aging Study (MMAS). MMAS included 1290 men (aged 40-70 years) and reported a 52% incidence of some degree of ED. Sildenafil and other PDE-5(Phosphodiesterase type-5) inhibitors will eventually be developed for a number of cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodelling and heart failure. A recent clinical study suggested that PDE-5 inhibitors might be a new class of drug that can potentially be used for the treatment of essential hypertension. The unique mechanism of action and high efficacy of PDE5 inhibitors has generated immense interest among researchers dealing with sexual dysfunction. The recognition of ED as a warning sign of silent vascular disease has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise.
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PMID:ERECTILE DYSFUNCTION AS A PREDICTOR OF CARDIOVASCULAR DISEASE. 2813 40

PDE type 5 inhibitors (PDE5Is), such as sildenafil, tadalafil and vardenafil, are a class of drugs used to prolong the physiological effects of NO/cGMP signalling in tissues through the inhibition of cGMP degradation. Although these agents were originally developed for the treatment of hypertension and angina, unanticipated side effects led to advances in the treatment of erectile dysfunction and, later, pulmonary arterial hypertension. In the last decade, accumulating evidence suggests that PDE5Is may confer a wider range of clinical benefits than was previously recognised. This has led to a broader interest in the cardiovascular therapeutic potential of PDE5Is, in conditions such as hypertension, myocardial infarction, stroke, peripheral arterial disease, chronic kidney disease and diabetes mellitus. Here, we review the pharmacological properties and established licensed uses of this class of drug, along with emerging therapeutic developments and possible future indications.
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PMID:Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease. 3172 Nov 65