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)

Several large, carefully randomized studies of pharmaceutical agents in the treatment of patients with congestive heart failure (CHF) and left ventricular dysfunction have demonstrated conclusively that angiotensin-converting enzyme (ACE) inhibitors reduce mortality among patients with CHF, as well as the number of hospitalizations for heart failure, myocardial infarction (MI), and angina. ACE inhibitors also have been shown to prevent the development of heart failure in patients with asymptomatic left ventricular dysfunction. Phosphodiesterase inhibitors and the beta agonists have been shown to increase mortality with no beneficial effect on morbidity. The role of digitalis remains controversial. On the one hand, the limited data available suggest that digoxin prevents clinical deterioration in patients with heart failure, even in the presence of sinus rhythm. On the other hand, when administered after MI, digoxin has been associated with increased mortality. Such conclusions are unreliable, however, since it is impossible to adjust statistically for the fact that digoxin is used in sicker patients. This question will be addressed in a large randomized study currently being conducted by the Digitalis Investigation Group. Pharmacologic approaches to the reduction of sudden death currently being explored include amiodarone, oral magnesium supplements, and beta blockers. According to the Cardiac Arrhythmia Suppression Trial and other studies, the class I antiarrhythmic agents appear unpromising or even harmful. The calcium channel blockers also appear to be contraindicated as routine therapy for CHF.
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PMID:Clinical experience in protecting the failing heart. 850 87

Cyclic nucleotides are important secondary messengers that control many physiologic processes, including smooth muscle contractility. Phosphodiesterases (PDEs) comprise of a superfamily of metallophosphydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5' nucleotide. Currently 21 PDE genes have been cloned and are classified into 11 families (1-11) according to their sequence of homology, biochemical and pharmacological properties. Phosphodiesterase type 5 (PDE5) is one of the members of the superfamily that specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. It is composed of 875 amino acids and was first identified in lungs, vascular and tracheal smooth muscle, and platelets. PDE5 is selectively inhibited by sildenafil, vardenafil and tadalafil, and less selectively by zaprinast and dipyridamole. PDE5 inhibitors have been reported to possess antiplatelet aggregation, weak cardiac inotropic effects and vascular relaxant properties. The tissue distribution of the PDE5 family is relatively restricted compared with other PDEs. Still, recent immunohistochemical and reverse transcriptase-polymerase chain reaction analysis have demonstrated the presence of anti-PDE5 antibodies and PDE5 transcripts in rat cerebellum, kidney, pancreas, aortic smooth muscle cells, heart, placenta, skeletal muscle, and, to a much lesser extent, in other regions of the brain, liver and lungs. Research in this field is intense, with a goal of identifying and developing new, selective PDE5 inhibitors that would be beneficial in a number of maladies, as well as angina, hypertension and erectile dysfunction (ED).
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PMID:Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects. 1567 22

Phosphodiesterase 5 (PDE5) inhibitors have modest nitrate-like hemodynamic effects, lowering wedge pressure, pulmonary artery pressure, and systolic and diastolic arterial pressure. At rest, decreases in arterial pressure averaging 9/8 mm Hg may increase to 12/5 mm Hg as a result of the vasodilatory response, but no clinical adverse effects have been reported. On the background of increased vasoconstriction related to elevation of angiotensin II, a greater decrease may occur and be relevant to cardiovascular therapy, particularly if angiotensin II antagonists are coprescribed. Exercise studies in patients with ischemia identified no adverse event potential for sildenafil, vardenafil, and tadalafil. Another study showed sildenafil had an anti-ischemic effect, increasing time to limiting angina. Evidence supports the safety of these agents in patients with chronic stable coronary artery disease (CAD). With accumulating evidence of benefits on endothelial function and clinical improvements in pulmonary hypertension and heart failure, the hemodynamic and exercise effects of PDE5 inhibitors suggest an important therapeutic cardiovascular role, reinforcing their safety in the patient with CAD and erectile dysfunction.
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PMID:Hemodynamic and exercise effects of phosphodiesterase 5 inhibitors. 1638 64

Phosphodiesterase 5 (PDE5) selectively hydrolyzes cyclic guanosine monophosphate. Inhibitors of PDE5 were originally developed to treat angina pectoris, and currently have multiple therapeutic indications, including erectile dysfunction and pulmonary hypertension. Several lines of research have provided evidence to support various potential PDE5-dependent cellular mechanisms in the myocardium that are involved in the pathophysiology of heart failure and cardiac dysfunction. In this Review we provide a mechanistic overview of the pharmacological inhibition of PDE5 in the context of heart failure, and evaluate the evidence supporting the use of novel PDE5 inhibitors in the treatment of this condition.
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PMID:Phosphodiesterase 5 inhibition in heart failure: mechanisms and clinical implications. 1937 97

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