Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intermittent claudication (IC) is leg muscle pain, cramping and fatigue brought on by exercise and is the primary symptom of peripheral arterial disease. The goals of pharmacotherapy for IC are to increase the walking capacity/quality of life and to decrease rates of amputation. In 1988, pentoxifylline was the only drug that had reasonable supportive clinical trial evidence for being beneficial in IC. Since then a number of drugs have shown benefit or potential in IC. Cilostazol, a specific inhibitor of phosphodiesterase 3 and activator of lipoprotein lipase, clearly increases pain-free and absolute walking distances in claudicants. However, cilostazol does cause minor side effects including headache, diarrhoea, loose stools and flatulence. Naftidrofuryl, a serotonin (5-HT2) receptor antagonist and antiplatelet drug, is beneficial in claudicants. Inhibitors of platelet aggregation (including nitric oxide from L -arginine or glyceryl trinitrate) and anticoagulants (low molecular weight heparin, defibrotide) probably have both short and long-term benefits in IC. In addition, intravenous infusions of prostaglandins (PGs) PGE1 and PGI2 have an established role in severe peripheral arterial disease and the recent introduction of longer lasting and/or oral forms of the PGs makes them more likely to be useful in the IC associated with less severe forms of the disease. There are some exciting new approaches to the treatment of IC, including propionyl-L-carnitine and basic fibroblast growth factor (bFGF).
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PMID:Pharmacotherapy of intermittent claudication. 1182 12

IC351 (tadalafil, trade name Cialis) is a new representative compound of the second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7 through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the efficacy rates were up to 93% for successful intercourses with completion in the 50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up to 88% improvement in erections and up to 73% successful intercourses with completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg) trial in diabetic patients, improved erections of 56% and 64% were reported compared with 25% after placebo. Drug-related adverse effects, with headache in up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1% (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious cardiovascular adverse events nor color vision disturbances were encountered. The long half-life (>17 h), with a comfortably long window of opportunity, releases couples from the need to plan sexual activities and therefore provides the highest amount of spontaneity for sexual activities.
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PMID:IC351 (tadalafil, Cialis): update on clinical experience. 1185 Jul 37

The potential mechanisms underlying back pain and/or myalgia experienced by men taking tadalafil were investigated. An integrated analysis of 10 placebo-controlled tadalafil clinical trials (N=1846) showed that the incidence of back pain and/or myalgia was 9.4% in patients receiving tadalafil 10 mg (N=394), 8.3% in patients receiving tadalafil 20 mg (N=883) and 3.7% in placebo-treated patients (N=569). One (0.3%) patient receiving tadalafil 10 mg, six (0.7%) patients receiving tadalafil 20 mg, and no patients receiving placebo discontinued treatment due to back pain and/or myalgia. In a prospective study in healthy volunteers, no substantial changes were observed in laboratory markers indicative of inflammation or muscle damage, and tadalafil did not affect renal plasma flow nor produce lumbar or gluteal myositis by positron emission tomography scan or magnetic resonance imaging. Although the mechanism of back pain and/or myalgia remains unknown, these events appear to be self-limiting and a general effect of phosphodiesterase 5 inhibition.
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PMID:A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia. 1603 69

There are no published controlled clinical trials of regular phosphodiesterase type 5 inhibitor therapy as a long-term treatment of hypertension. In a randomized, double-blind, 2-way crossover study, 25 otherwise untreated hypertensive subjects were administered 50 mg of sildenafil or matched placebo 3 times daily for 16 days, and the effects on ambulatory blood pressure (BP), clinic BP, arterial wave reflection, carotid-femoral pulse wave velocity, and brachial artery flow-mediated dilatation were assessed. Three subjects were withdrawn because of adverse effects, and the data from the remaining 22 subjects were analyzed. Sildenafil reduced ambulatory BP (mean [SE] change from baseline for average daytime BP: systolic -8 [2] mm Hg versus 2 [2] mm Hg with placebo, P<0.01; diastolic -6 [1] mm Hg versus 0 [1] mm Hg, P<0.01) and clinic BP (change from baseline to 1 hour after drug administration on day 16: systolic -5 [2] mm Hg versus 4 [2] mm Hg, P<0.01; diastolic -5 [1] mm Hg versus 2 [2] mm Hg, P<0.01). Compared with baseline, sildenafil, but not placebo, reduced arterial wave reflection both acutely and after chronic treatment, but the chronic change in arterial wave reflection was not statistically different from the chronic change with placebo. Sildenafil did not affect pulse wave velocity or flow-mediated dilatation. The main adverse effects of sildenafil, which were generally transient and rated as mild or moderate in severity, were dyspepsia, headache, and myalgia. In conclusion, regular sildenafil constitutes effective antihypertensive therapy. Further studies are warranted to evaluate the role of longer-acting phosphodiesterase type 5 inhibitors as antihypertensive agents in clinical practice.
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PMID:Effect of regular phosphodiesterase type 5 inhibition in hypertension. 1744 22

Erectile dysfunction is a common multifactorial complication of diabetes mellitus. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. A recent Cochrane systematic review assessed the effects ofPDE-5 inhibitors in patients with diabetes mellitus and erectile dysfunction from 8 randomized placebo-controlled trials (a total of 1759 participants). The duration of therapy was mainly 12 weeks. The weighted mean difference (WMD) for the International Index of Erectile Function (erectile dysfunction domain) at the end of the study period was 6.6 in favour of the PDE-5 inhibitors arm. The relative risk for answering 'yes' to a global efficacy question ('did the treatment improve your erections?') was 3.8 in the PDE-5 inhibitors arm compared with the control arm. Headache and flushing were the most common adverse events, followed by flu-like symptoms, dyspepsia, myalgia, vision disorders and lower back pain. The overall risk ratio for developing any adverse reaction was 4.8 in the PDE-5 inhibitors arm as compared to the control arm. It was concluded that sufficient evidence exists that treatment with PDE-5 inhibitors can improve erectile dysfunction in diabetic men.
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PMID:[From the Cochrane Library: Phosphodiesterase inhibitors are effective in treating erectile dysfunction in diabetic men]. 1794 26

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least "typical" PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.
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PMID:Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence. 1804 21

A 66-year-old man with diabetes and hypertension using statin was admitted to the hospital with progressive myalgia. He had been on rosuvastatin for five months. After beginning the use of phosphodiesterase-5 inhibitors, he presented with severe muscle pain and maintained penile erection. Several days after interruption of therapy, muscle pain and penile erection disappeared. This case demonstrates the interaction of sildenafil with rosuvastatin might result in myopathy.
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PMID:Rhabdomyolysis induced by rosuvastatin and sildenafil. 2081 98

The pathology of pulmonary arterial hypertension (PAH) is characterized by vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. Experimental studies have shown the beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil which significantly improve clinical status, exercise capacity and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in management of PAH. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia.
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PMID:[Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension]. 2081 51

Selective phosphodiesterase type 5 inhibitors (PDE5Is) have revolutionized the treatment of erectile dysfunction (ED) in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.
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PMID:A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy. 2085 43