naloxone and Lung-Diseases--Obstructive

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

Dyspnea is a common symptom in patients with chronic obstructive pulmonary disease (COPD) but its mechanism is unclear. It is known that the opiate antagonist, naloxone, restores in some patients with COPD the ability to compensate for a flow-resistive load (N Engl J Med 1981; 304; 1190-5). We studied the effect of naloxone on the threshold of resistive load detection (RLD) and on sensation of breathlessness in patient with COPD. Naloxone (NLX, 2mg, IV) and placebo (P, Physiologic saline, 10ml) were administered in a randomized double-blind fashion, on separate days, to sixteen patients. The threshold for RLD was assessed by added resistance (delta R; 0.3-6.9cmH2O/L/sec) where the subject detected the load 50% of the time. This was analyzed in two ways; one by the ratio of added resistance divided by background resistance (Ro) and the other, by the mouth pressure (P) at the threshold. The patient squeezed a handgrip as ventilation increased and perception of breathlessness was assessed by a degree of squeezed handgrip (Gf; 0-100%). The threshold for breathlessness was estimated by Gf divided by ventilatory volume (Gf/VE) and P0.1 at the point of endtidal PCOz of 50mmHg (Gf/P0.1%/cmH2O), respectively. The threshold for RLD remained unchanged but Gf/VE increased significantly after NLX instillation (delta R/Ro: 0.55 +/- 0.28 during P vs 0.52 +/- 0.36 during NLX, NS. P: 0.89 +/- 0.44 during P vs 0.97 +/- 0.54 during NLX, NS. Gf/VE: 0.76 +/- 0.57 during P vs 1.38 +/- 0.62 during NLX, P < 0.01). FRC, VE, f, T1, TE and P0.1 did not significantly change after NLX.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Double-Blind Method; Endorphins; Female; Homeostasis; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Pulmonary Gas Exchange; Respiration

To assess the role of endogenous opioid peptides in ventilatory control in patients with chronic obstructive lung disease, we measured the ventilatory and mouth occlusion pressure responses to hypercapnia and the compensatory response to an inspiratory resistive load in 11 male patients with COPD before and after intravenous administration of naloxone or placebo on 2 separate days. There were no statistically significant differences between naloxone and placebo administration in any index of ventilatory response to CO2 or resistive loading. When an inspiratory resistive load was added during CO2 rebreathing, minute ventilation at PETCO2 = 50 mm Hg in all 11 patients decreased significantly (p less than 0.05) with placebo and naloxone. In response to the inspiratory resistive load, in eight of the 11 patients mouth occlusion pressure (P0.1) did not increase; these eight subjects were classified as noncompensators. Naloxone did not affect the P0.1 response to inspiratory resistive loading, either in the group as a whole or in the subgroup of eight patients classified as noncompensators. Our study was unable to demonstrate that increased activity of endogenous opioid peptides suppresses the ventilatory response to CO2 or resistive loading in patients with chronic obstructive lung disease.

Topics: Aged; Clinical Trials as Topic; Double-Blind Method; Humans; Hypercapnia; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Random Allocation; Respiration

Elevated endorphin levels in patients with COPD may act to diminish the sensation of dyspnea. Exogenous opioids decrease exertional dyspnea and increase exercise capacity in COPD patients. The purpose of this study was to determine the effects of endogenous opioids on the exercise capacity and control of breathing in patients with COPD. We hypothesized that naloxone, an opioid antagonist, would block the endogenous endorphins and decrease the exercise capacity of our patients. Six patients (mean age, 58.8 +/- 3.2 years) with COPD (mean FEV1, 1.28 +/- 0.46 L) underwent identical incremental cycle ergometer tests to exhaustion (Emax) and assessment of their hypercapnic and hypoxic ventilatory responses and mouth occlusion pressure responses following the IV administration of naloxone (0.4 mg/kg) (N) or placebo (P) in a randomized, double-blind fashion. Perceived dyspnea (modified Borg scale), breathing patterns, and expired gas levels were compared at rest and at maximal workload (WL). There was no significant difference after N compared with after P in the WL or the duration of work. At Emax there were no significant differences after N compared with after P in ventilation, the level of dyspnea, P0.1, VO2, or VCO2. The ventilatory response to CO2 production during exercise (delta VE/delta VCO2) and the ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia did not differ significantly after N compared with after P. This study does not support the hypothesis that endogenous opioids play a significant role in dampening dyspnea and facilitating exercise in patients with COPD.

Topics: Double-Blind Method; Endorphins; Exercise; Exercise Test; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Randomized Controlled Trials as Topic; Respiration

In a randomized double-blind design 10 patients with decompensated COPD received intravenous naloxone (2 mg) and placebo. Arterial gases were monitored at 15, 30 and 60 min. No significant changes were observed in pCO2 after naloxone as compared to placebo.

Topics: Blood Gas Analysis; Humans; Lung Diseases, Obstructive; Naloxone; Respiration; Respiratory Insufficiency

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

Recent reports suggest that endogenously released endorphins may exert a modifying influence on respiratory center drive in patients with respiratory disease. In this report, we employed respiratory inductive plethysmography to noninvasively assess breathing patterns with particular attention to respiratory center drive as reflected by mean inspiratory flow. We studied 10 patients with documented chronic obstructive pulmonary disease (6 with hypercapnia and 4 with normocapnia) after treatment with placebo and the opiate antagonist, naloxone. No significant change in breathing pattern was observed in either patient group after treatment with placebo or naloxone, although individual patients displayed greater respiratory drive after naloxone than placebo. Therefore, endorphins do not exert a consistent influence on respiratory center output in patients with chronic obstructive pulmonary disease.

Topics: Aged; Female; Humans; Hypercapnia; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Plethysmography; Respiration

To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.

Topics: Adult; Aged; Bronchitis; Double-Blind Method; Endorphins; Female; Humans; Hypercapnia; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Random Allocation; Respiration; Respiratory Function Tests

We report a patient with COPD and bullous emphysema treated with narcotic antagonists (naloxone and naltrexone) for severe respiratory failure, with hypoxemia and hypercapnia, non responding to traditional medical therapy. According to previous reports, this treatment was started while waiting for lung transplantation, and it improved clinical pattern and arterial blood gas levels. Though the patient died for left ventricular failure fifteen days after the beginning of therapy, we think that narcotic antagonists can be successfully administered in some patients with advanced stage COPD.

Topics: Humans; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Naltrexone; Pulmonary Emphysema; Tomography, X-Ray Computed

Topics: Humans; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Naltrexone

The narcotic antagonists naloxone and naltrexone were used as respiratory stimulants in two patients failing traditional medical therapy for COPD. Both patients demonstrated improvement while receiving the drugs, but developed respiratory failure when they were discontinued abruptly. In selected patients with COPD, narcotic antagonists may offer an additional mode of therapy.

Topics: Aged; Carbon Dioxide; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Naloxone; Naltrexone; Oxygen

Ventilatory and airway occlusion pressure responses to hypoxia were measured in 7 subjects with chronic obstructive pulmonary disease (COPD). Paired responses were obtained after the administration of saline or naloxone and, on separate days, in 5 of the 7 subjects, after 2 saline injections. Naloxone increased (p less than 0.05) the mean inspiratory flow and the ventilatory and airway occlusion pressure responses to hypoxia when compared with the saline responses. Resting ventilation and tidal volume also increased, but not significantly. Involvement of endogenously generated opioid substances in the control of breathing of patients with COPD is further suggested by this study.

Topics: Humans; Hydrogen-Ion Concentration; Hypoxia; Lung Diseases, Obstructive; Naloxone; Pressure; Pulmonary Ventilation; Respiration; Spirometry; Tidal Volume; Time Factors

Since narcotic drugs profoundly depress breathing, we tested whether endogenous opioids influenced control of breathing in chronic obstructive pulmonary disease (COPD), reasoning that the stress of chronic dyspnea might cause elaboration of "endorphins." In 14 patients with COPD (but without respiratory failure) and eight normal controls, we measured ventilation, mechanical lung function, respiratory sensitivity to carbon dioxide, and the increase in respiratory effort elicited by an increase in resistance to breathing; each measurement was performed before and after administration of the opiate antagonist naloxone. Before naloxone, increased resistance to breathing enhanced respiratory effort in all controls, but seven of 14 patients with COPD had no response. After naloxone, these seven patients had load responses. Furthermore, the respiratory effort elicited by the resistance also increased after the drug was given to the patients who had had a response. These data suggest that endorphin elaboration minimizes the stress of chronic airway obstruction.

Topics: Aged; Carbon Dioxide; Endorphins; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Middle Aged; Naloxone; Oxygen; Partial Pressure; Respiration; Vital Capacity

Topics: Animals; Cats; Endorphins; Female; Fetal Hypoxia; Humans; Lung Diseases, Obstructive; Naloxone; Pregnancy; Rabbits; Respiration; Sheep

Topics: Endorphins; Hypercapnia; Lung Diseases, Obstructive; Naloxone; Respiration

The anesthesiologist uses a wide spectrum of drugs, including inhalational general anesthetics, barbiturates, benzodiazepines, narcotics analgesics and their antagonists, and neuromuscular blocking drugs. All of these drugs in sufficient dose impair the ventilatory response to chemical stimuli, and may cause inadequate gas exchange. The effect of depression of ventilatory control depends on the magnitude of depression and the coexistence of functional abnormalities in the respiratory system. The functional abnormalities are the result of preexistent pulmonary disease or other disease processes that impair respiratory function, the anticipated effects of major surgery (e.g., pulmonary resection), and the complications of anesthesia and surgery. From a functional viewpoint, the mechanisms of the effects of these disease processes on ventilatory control are: (1) interference with the neurophysiological control of automatic ventilation; (2) impairment of peripheral or central chemoreceptor function; (3) impairment of respiratory muscle function; (4) increase in the mechanical load to breathing as a result of increased resistance or decreased compliance of the respiratory system; and (5) increase in the ventilatory requirements as a result of ventilation/blood flow maldistribution, metabolic acidosis, or increased metabolic rate. As a result of current trends in the use of multiple drugs and controlled ventilation during anesthesia, the patient is at greatest risk during the early postoperative period in the recovery room. In addition to the functional abnormalities described above, the probability of impaired gas exchange and respiratory failure is increased as a result of impaired metabolism and elimination of drugs as a result of hepatic and renal insufficiency, and acute changes in acidbase status, which alter the ionization and distribution of drugs.

Topics: Anesthetics; Anti-Anxiety Agents; Autonomic Nervous System; Barbiturates; Benzodiazepines; Carbon Dioxide; Fentanyl; Halothane; Humans; Hyperthyroidism; Hypoxia; Lung Diseases, Obstructive; Meperidine; Methoxyflurane; Morphine; Naloxone; Neuromuscular Blocking Agents; Neuromuscular Diseases; Obesity; Pulmonary Edema; Pulmonary Fibrosis; Respiration; Scoliosis