Acute and chronic effects of low dose almitrine bismesylate in the treatment of chronic bronchitis and emphysema.

OBJECTIVES: Study of the acute and chronic effects of low-dose almitrine therapy in stable hypoxaemic patients with chronic bronchitis and emphysema. METHODS: A low daily dose of 75 mg almitrine bismesylate was administered for six months in 23 patients with chronic bronchitis and emphysema. Nine patients (group 1) were placed on oral almitrine bismesylate 25 mg t.i.d. after they had received a single intravenous dose of 60 mg almitrine three months earlier. Fourteen additional patients, seven receiving almitrine (group 2) and seven placebo (group 3) were randomized for a 6 month double-blind evaluation of both acute and chronic effects of 75 mg almitrine on pulmonary gas exchange and on pulmonary haemodynamics. All patients were followed-up with regular measurements of blood gases, body plethysmography and with evaluation of peripheral nerve function. RESULTS: Acute effects of almitrine were a significant increase in arterial oxygen tension by 14 mmHg after intravenous (p < 0.001) and by 15 mmHg after oral administration (p < 0.001), amelioration of hypercapnia, a slight transient increase in mean pulmonary artery pressure from 26 +/- 7 to 29 +/- 6 mmHg (NS) and a decrease of shunt due to improvement in ventilation/perfusion mismatching. In contrast, no acute changes in blood gases and pulmonary pressures were seen in the placebo group. A combination of almitrine with oxygen (8-10 L/min) was most effective in amelioration of hypoxaemia and shunt. With chronic almitrine therapy, the improvements in gas exchange persisted without elevation of pulmonary artery pressure (26 +/- 8 mmHg), whereas a negative trend in change of blood gases and pulmonary artery pressure occurred in the placebo treated group (NS). No significant changes in external ventilation, other spirometric parameters or adverse effects concerning peripheral nerve function were seen after almitrine or placebo treatment. The elimination of almitrine was fitted to a three compartment model and the terminal half-life in the patient population was found to be 32 +/- 29 days after intravenous dosing. CONCLUSION: Acute and six-month almitrine bismesylate therapy at a low daily dose of 75 mg is found to be safe, even in severely compromised patients, with regard to pulmonary haemodynamics and peripheral nerve function. The agent is beneficial to pulmonary gas exchange, with reduction of hypercapnia, of intrapulmonary shunt and also with regard to sustained elevation of arterial oxygen tension. A combination with inhaled oxygen seems especially efficacious.

Lack of effect of enoximone on the pharmacokinetics of digoxin in patients with congestive heart failure.

The aim of this study was to investigate if the concomitant administration of the positive inotropic drug enoximone (100 mg tid) has any effect on the morning through levels of the cardiac glycoside digoxin in 17 patients with congestive heart failure (NYHA II-IV). Plasma concentrations of digoxin were 1.05 +/- 0.37 ng/mL before enoximone, 0.95 +/- 0.31 ng/mL at the end of the enoximone treatment period of 1 week and 0.95 +/- 0.36 ng/mL 1 week after cessation of enoximone treatment. Thus, concomitant administration of enoximone had no effect on plasma concentrations of digoxin while on the other hand the hemodynamics as assessed by NYHA-classification and determination of the heart volume improved significantly.

[Steroid-refractory amiodarone-induced pulmonary fibrosis. Clinical features and morphology after an amiodarone-free interval of 3 months]. / Steroidrefraktäre Lungenfibrose durch Amiodaron. Klinik und Morphologie nach einem amiodaronfreien Intervall von 3 Monaten.

Amiodarone-induced bilateral diffuse pulmonary fibrosis developed in a 47-year-old woman with idiopathic hypertrophic subvalvular aortic stenosis who had been treated with amiodarone (Cordarex), 300 mg daily for about 18 months. Although the drug was discontinued and cortisone treatment begun, the pulmonary fibrosis did not regress. When gentamicin (Refobacin) and cefotaxime (Claforan) were administered for suspected fibrosis-induced right-sided bronchopneumonia, gentamicin-induced acute tubular renal damage occurred, requiring dialysis. The patient died soon after of myocardial electro-mechanical dissociation. At necropsy there was, in addition to the idiopathic hypertrophic subvalvular cardiomyopathy, extensive bilateral pulmonary fibrosis, lamellar bodies in foam-cell intraalveolar macrophages, in hepatocytes and in the epithelium of the proximal and distal tubules. Although amiodarone had been discontinued three months previously, high concentrations of the drug were still present, especially in both lungs, fat tissue and the liver.

Isometric exercise for the evaluation of vasodilatory therapy in severe congestive heart failure.

There are few data available about the hemodynamic effects of isometric handgrip in severe congestive heart failure and its role in the evaluation of vasodilatory therapy. Therefore, we studied 20 patients with dilated cardiomyopathy at rest, during isometric handgrip, and during supine bicycle exercise before and after a single 25-mg dose of captopril. During handgrip, heart rate (p less than 0.001); systemic vascular resistance (p less than 0.01); systolic, mean, and diastolic pulmonary artery pressure (p less than 0.01) increased significantly; stroke volume index fell (p less than 0.05); whereas mean arterial pressure showed only a small increase, and cardiac index did not change. In contrast, mean arterial pressure and cardiac index increased during dynamic exercise (p less than 0.001), and peripheral resistance decreased (p less than 001). During both handgrip and bicycle exercise, captopril induced a decrease of arterial pressure (p less than 0.01 and p less than 0.001; respectively), peripheral resistance (p less than 0.001 and p less than 0.01; respectively), and systolic (p less than 0.01 and p less than 0.001, respectively) mean (p less than 0.001), and diastolic pulmonary artery pressure (p less than 0.001). Captopril induced and increase in stroke volume index (p less than 0.01) and cardiac index (p less than 0.001 and p less than 0.01 respectively) during both types of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)