Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary arterial hypertension (PAH) is a rare debilitating disease characterized by an increase in pulmonary vascular resistance and progressive right ventricular failure. PAH may be primary or associated with other conditions such as collagen vascular disease, portal hypertension, and HIV. Intravenous epoprostenol improves the survival, exercise tolerance, hemodynamics, and quality of life in patients with PAH and is believed to work through multiple pathways including vasodilation, opposition of smooth-muscle hypertrophy, and inhibition of platelet aggregation. Common dose-limiting side effects are flushing, jaw pain, arthralgias, myalgias, and headache, which are attributed to the vasodilatory effects of epoprostenol. In clinical practice, patients often develop persistent rash that is distinct from the flushing associated with epoprostenol. The specific findings both on physical examination and on dermatopathology have not, however, been well described. This report describes the cutaneous and dermatopathologic findings of 12 patients who developed persistent rash while receiving long-term prostacyclin for PAH.
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PMID:Cutaneous findings in patients with pulmonary arterial hypertension receiving long-term epoprostenol therapy. 1524 33

Pulmonary arterial hypertension (PAH) is a rare disease characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary arterial resistance, right heart failure, and death. The pathogenesis of PAH is multifactorial, with endothelial cell dysfunction playing an integral role. This endothelial dysfunction is characterized by an overproduction of vasoconstrictors and proliferative factors, such as endothelin-1, and a reduction of vasodilators and antiproliferative factors, such prostacyclin and nitric oxide. Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. PDE-5 is abundantly expressed in lung tissue, and appears to be upregulated in PAH. Three oral PDE-5 inhibitors are available (sildenafil, tadalafil, and vardenafil) and are the recommended first-line treatment for erectile dysfunction. Experimental studies have shown the beneficial effects of PDE-5 inhibitors on pulmonary vascular remodeling and vasodilatation, justifying their investigation in PAH. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil, which are therefore currently the approved PDE-5 inhibitors in PAH treatment. Sildenafil and tadalafil 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 the management of PAH although further studies are needed in this area. 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. Mild and moderate renal or hepatic failure does not significantly affect the metabolism of PDE-5 inhibitors, whereas coadministration of bosentan decreases sildenafil and tadalafil plasma levels. Due to their clinical effectiveness, tolerance profile, and their oral administration, sildenafil and tadalafil are two of the recommended first-line therapies for PAH patients in World Health Organization functional classes II or III.
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PMID:Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension. 1976 39

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by increasing pulmonary vascular resistance leading to right ventricular failure and death. Treprostinil is a stable prostacyclin analog approved for the treatment of PAH to improve exercise capacity. In the setting of PAH, the major pharmacological actions of treprostinil include vasodilatation of the pulmonary and systemic vascular beds, inhibition of platelet aggregation and inhibition of smooth muscle cell proliferation. Treprostinil therapy may be delivered via parenteral (subcutaneous and intravenous) or inhaled routes of administration, with oral tablets in the later stages of clinical development. In clinical trials, treprostinil has been shown to improve clinical status, functional class, exercise capacity and quality of life. Common side effects of treprostinil therapy include headache, flushing, jaw pain, diarrhea, and for subcutaneous administration, infusion site pain or reaction. This article provides an overview of treprostinil therapy for the treatment of PAH with a focus on the available efficacy and safety data for parenteral, inhaled and oral administration.
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PMID:Treprostinil for the treatment of pulmonary arterial hypertension. 2325 41

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that is associated with severe functional impairment and a poor prognosis. Ambrisentan is a selective endothelin type A receptor antagonist approved for the treatment of patients with PAH World Health Organization group 1. The efficacy and safety of ambrisentan has been evaluated in the ARIES series (Ambrisentan for the Treatment of Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies), which has established its use as both monotherapy or in conjunction with other PAH therapies. Specifically, ambrisentan is effective at increasing exercise tolerance, decreasing the risk of functional class deterioration, and prolonging time to clinical worsening. Further, ambrisentan has a favorable effect on mortality, with an 88% patient survival rate after two years of therapy compared with a 61% survival rate as estimated by the National Institute of Health Registry. Ambrisentan is generally well tolerated in all patient groups, with the main side effects of peripheral edema, sinusitis, flushing, and nasal congestion considered to be mild to moderate in nature. Ambrisentan has several favorable qualities that potentially make it more acceptable to patients, including once-daily administration, limited adverse drug reactions and drug-drug interactions, and minimal risk of liver enzyme elevation. Because of the potential risk of teratogenicity associated with ambrisentan, it is only available through a limited distribution program, ie, LEAP (the Letairis Education and Access Program). Ongoing clinical trials will help to clarify the role of ambrisentan in the treatment of PAH.
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PMID:Ambrisentan for the treatment of pulmonary arterial hypertension: improving outcomes. 2367 88

Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that progresses rapidly and is currently without a cure. Pharmacological treatments aim to slow down disease progression and to reduce symptoms by targeting the prostacyclin, the endothelin or the nitric oxide pathway. Drugs targeting the prostacyclin pathway have been shown to be favourable for PAH patients by causing vasodilatative, anti-proliferative as well as anti-inflammatory effects, but tend to be underused, partially due to adverse effects and difficulties associated with their intravenous administration. Treprostinil, a stable prostacyclin analogue, was FDA-approved in 2002 to improve exercise capacity in PAH patients and is available in intravenous, subcutaneous, inhaled and oral form. The four different possible ways of administration, a long half-life and its stability at room temperature give treprostinil an advantage over epoprostenol, iloprost and selexipag, the three other FDA-approved drugs targeting the prostacyclin pathway. In clinical trials, treprostinil improved exercise capacity, quality of life (QOL), functional class and clinical status. While the different forms of treprostinil lead to specific complications, its general adverse effects are dizziness, nausea, pain in the jaw and extremities, diarrhoea, flushing and headache. This MiniReview will assess the benefits and drawbacks of treprostinil in the treatment of PAH by examining its specific mechanism of action and pharmacological properties, such as pharmacokinetics, pharmacodynamics, adverse effects and interactions. In addition, we will analyse and discuss results from different clinical trials, comparing treprostinil's four different forms to each other as well as to other drugs targeting the prostacyclin pathway.
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PMID:The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. 3140 54