Evaluation of Imatinib Mesylate in the Treatment of Pulmonary Arterial Hypertension

Imatinib mesylate is a small molecule inhibitor that selectively inhibits the PDGF receptor kinase as well the cKIT and Abl kinases, among other targets. Various studies have implicated the PDGF pathway in the pathogenesis of pulmonary arterial hypertension (PAH). Inhibition with imatinib mesylate has shown efficacy in human case reports and experimental models of PAH. Results from a Phase II trial of imatinib mesylate in PAH did not meet the primary end point but showed improvement in several secondary end points and in a subgroup analysis. As suggested by this study as well as a few case reports, imatinib may be effective in a subset of patients with more severe disease. However, this remains to be further validated through a Phase III study, which is already underway. In conclusion, it appears that imatinib mesylate may hold promise as an adjunct drug in PAH therapy, especially since it is directed at a pathway not previously targeted. …

Acquired Methemoglobinemia: A Case Report of Benzocaine-Induced Methemoglobinemia and a Review of the Literature

Benzocaine is widely used as a topical anesthetic and is also present in a number of over-the-counter preparations. Methemoglobinemia is a rare, but potentially serious, complication of its use; a fact that is not well documented in the Physician’s Desk Reference or product inserts. Unfamiliarity with this complication may delay diagnosis and appropriate therapy. A case of methemoglobinemia occurring as a complication of using benzocaine during bronchoscopy is presented and is followed by a review of the literature and discussion of the pathophysiology, clinical presentation, diagnosis, and treatment of acquired methemoglobinemia. Methemoglobin is incapable of carrying oxygen and is formed when the ferrous iron in the heme molecule is oxidized to the ferric state. The normal mechanisms that convert methemoglobin back to hemoglobin can be overwhelmed by many oxidant drugs, resulting in toxic methemoglobinemia. The diagnosis should be entertained when cyanosis, unresponsive to 100% oxygen therapy, appears suddenly, especially when exposure to an oxidant drug is established. Diagnosis is confirmed by multiple-wavelength cooximetry. Most cases require only decontamination and supportive care. Methylene blue is the specific antidote, but should be reserved for more severe cases or if comorbid conditions make mild hypoxia unadvisable. Exchange transfusion or hemodialysis may be indicated in patients who fail to respond to methylene blue. …

Exercise Prescription for Patients With Chronic Lung Disease

Chronic lung disease (CLD) and any consequent disease-related muscle myopathy along with deconditioning can cause both dyspnea and/or leg discomfort during exertion. These unpleasant experiences frequently lead an individual to reduce or even eliminate daily tasks which adversely impacts quality of life for the individual. The primary goal of exercise training is to restore the individual patient to the highest possible level of independent function. Improvements in exertional breathlessness observed following an exercise training program may be due to a physiologic training effect, enhanced mechanical efficiency, and/or psychologic desensitization. Any symptomatic patient with CLD who is motivated to participate should be referred to a pulmonary rehabilitation program. Exercise prescription is based on the principle of “overload” training. Although there is no optimal or best training regimen established for patients with CLD, we provide general guidelines for the mode, frequency, intensity, and duration of exercise training. The recommended minimal intensity of exercise training is 50% of peak work rate, although exercise at “maximal limits tolerated by symptoms” may also be prescribed. The recommended minimal duration of training is 20 to 30 minutes of continuous exertion. Resistance training should be incorporated into a comprehensive exercise program. One approach for patients with CLD to monitor their training intensity is to use a “dyspnea target” as a guide for intensity of training effort. …