Biomedical subjects

Richard Channick

Publications and source records attributed to Richard Channick.

6 recordsLinked to original sources

PubMed2006

Temporal trends and drug exposures in pulmonary hypertension: an American experience.

BACKGROUND: Reports have linked anorexigen intake to an increased risk of pulmonary arterial hypertension (PAH). With the rise in anorexigen use in the latter half of the last decade, we established a surveillance network within the United States to monitor temporal trends in the number of reported cases of PAH. We also studied whether use of anorexigens and other drugs differed among patients with pulmonary hypertension of different etiologies. METHODS: Newly diagnosed subjects (N = 1335) at 13 tertiary pulmonary hypertension centers were enrolled between January 1998 and June 2001. Patient-reported medication use was obtained by a telephone interview. Patients were classified as to the type of pulmonary hypertension. Poisson regression models were fitted to monthly case counts, and logistic regression methods were used to assess the association between type of pulmonary hypertension and medication use. RESULTS: The average monthly number of reported cases of PAH and other categories of pulmonary hypertension did not change over the study period. Fenfluramine or dexfenfluramine use during the 5 years before the time of the interview was preferentially associated with PAH. Fenfluramine/dexfenfluramine use was particularly common in cases referred but found not to have pulmonary hypertension. CONCLUSIONS: No epidemic of anorexigen-related PAH was evident during the study period. As persons who had taken fenfluramine or dexfenfluramine were particularly likely to be referred for evaluation of pulmonary hypertension, it is unlikely that the failure to detect an anorexigen-induced rise in primary pulmonary hypertension was because of underascertainment. The association between fenfluramine derivatives and PAH is consistent with the risk elevations previously reported.

Adolescent↗

PubMed2004

Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension.

Pulmonary hypertension (PH) is a disease of various origins. Nitric oxide-a potent vasodilator-is a key player of pulmonary vasoregulation. Nitric oxide signaling is mainly mediated by the guanylate cyclase/cyclic guanylate monophosphate pathway. The effects of this second messenger system are limited by enzymatic degradation through phosphodiesterases (PDEs). Recently, beneficial effects of the oral PDE-5 inhibitor sildenafil (originally approved for the treatment of erectile dysfunction) were reported for the treatment of PH. We provide a brief overview of the experimental and clinical application of PDE inhibitors in the field of PH. In particular, studies reporting the clinical effectiveness of sildenafil are highlighted. This agent, despite oral application, displays characteristics of a pulmonary selective vasodilator. In addition, evidence shows that sildenafil is operative mainly in the vasculature of well-ventilated areas of the lung. However, to date, controlled randomized trials proving the efficacy of this approach for the treatment of pulmonary arterial hypertension are lacking. The results of such studies have to confirm the current encouraging findings before recommendations regarding the use of PDE-5 inhibitors as a new treatment for PH can be made.

Animals↗

PubMed2004

Diagnosis and treatment of pulmonary arterial hypertension.

The diagnosis of pulmonary hypertension requires a high index of suspicion and careful attention to assessing the severity and classification of disease. Proper evaluation and understanding of determinants of severity in pulmonary arterial hypertension are necessary to guide appropriate therapy. This article discusses the diagnosis and treatment of this complex and multifactorial disease.

Humans↗

PubMed2004

Bosentan.

Bosentan (Tracleer, Actelion Pharmaceuticals Ltd) is an oral dual endothelin receptor antagonist approved for use in functional class III to IV pulmonary arterial hypertension. In two placebo-controlled trials, patients receiving bosentan showed improved functional class, 6-minute walk distance and hemodynamics over a 12- to 16-week period. Follow-up data over 3 years has shown few deteriorations,with the majority of patients maintaining their response to bosentan alone. Investigations exploring the use of bosentan as an add-on agent to intravenous epoprostenol (Flolan, GlaxoSmithKline Plc) in those with the most severe disease are ongoing. Bosentan may also have antifibrotic properties and its use in pulmonary fibrosis is being explored. Ease of administration of bosentan with twice-daily oral dosing will provide many patients with pulmonary hypertension an option for treatment without the risks and discomforts of continuous intravenous medication.

Administration, Oral↗

PubMed2003

Beraprost therapy for pulmonary arterial hypertension.

OBJECTIVES: The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death. Despite the risks from its delivery system, continuous intravenous epoprostenol remains the most efficacious treatment currently available. METHODS: A total of 116 patients with World Health Organization (WHO) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled. Patients were randomized to receive the maximal tolerated dose of beraprost sodium (median dose 120 microg four times a day) or placebo for 12 months. The primary end point was disease progression; i.e., death, transplantation, epoprostenol rescue, or >25% decrease in peak oxygen consumption (VO(2)). Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2), Borg dyspnea score, hemodynamics, symptoms of PAH, and quality of life. RESULTS: Patients treated with beraprost exhibited less evidence of disease progression at six months (p = 0.002), but this effect was not evident at either shorter or longer follow-up intervals. Similarly, beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m (p = 0.010 and 0.016, respectively) compared with placebo, but not at either 9 or 12 months. Drug-related adverse events were common and were related to the disease and/or expected prostacyclin adverse events. CONCLUSIONS: These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time.

Administration, Oral↗

PubMed2003

Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension.

OBJECTIVES: The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH). BACKGROUND: Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH. METHODS: Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment. RESULTS: Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (p = 0.057), RV:LV diastolic areas ratio = -0.64 (p = 0.007), Doppler RV index = -0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05). CONCLUSIONS: Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.

Administration, Oral↗