Respiratory diseases bronchodilators

Q4 What type of respiratory disease may produce the test results observed in this patient Would a bronchodilator drug be useful for Bob ... 

In recent years drug research in the respiratory area has been at an all-time high. Much of this work has stemmed from the discovery of cromolyn sodium as a truly new therapeutic modality as well as from a better appreciation of the pharmacodynamics of theophylline. Newer agents such as prostaglandin bronchodilators are now being studied extensively. One must feel that these extensive efforts will culminate in the development of better therapy for the patient suffering from respiratory disease. 

Research in respiratory disease at Mead Johnson has centered on heterocyclic molecules having a mixture of bronchodilator and antiallergic actions. One of these, an imidazopurinone (compound XI), recently emerged with particularly interesting pharmacologic features. Illustrated in Figure 6 are dose-response curves for intraduodenally administered compound XI in three appropriate tests in rats. 

Additional evidence for a corticosteroid effect In an allergic respiratory disease was furnished by a study"" In 52 asthmatic patients, showing an Inverse relationship between severity of asthma and steroid reserves In the adrenal cortex. In view of the prominent anti-Inflammatory action of the corticosteroids. It has been proposed that the steroids act only on the Inflammatory components of bronchial obstruction."" However, recent animal studies Indicate other mechanisms may be Involved in the bronchodilator effects of corticosteroids. Carrillo and Aviado"" determined the effects of hydrocortisone and dexamethasone on the histamine content and the mechanical properties of the lungs, in both sensitized and non-sensltlzed rabbits, and concluded that the steroids Induce broncho-dllatlon both by depletion of lung histamine and by direct bronchlolar smooth muscle relaxant action. 

Aerosol - Several serious adverse events occurred in severely ill infants with life-threatening underlying diseases, many of whom required assisted ventilation. Additional reports of worsening of respiratory status, bronchospasm, pulmonary edema, hypoventilation, cyanosis, dyspnea, bacterial pneumonia, pneumothorax, apnea, atelectasis, and ventilator dependence have occurred. Sudden deterioration of respiratory function has been associated with initiation of aerosolized ribavirin use in infants. If ribavirin aerosol treatment produces sudden deterioration of respiratory function, stop treatment and reinstitute only with extreme caution, continuous monitoring, and consideration of coadministration of bronchodilators. 

Respiratory smooth-muscle cells contain the beta-2 subtype of adrenergic receptors.76 (See Chapter 18 for a discussion of adrenergic receptor classifications.) Stimulation of these beta-2 receptors results in relaxation of bronchiole smooth muscle. Lienee, drugs that stimulate these beta-2 adrenergic receptors (i.e., beta-adrenergic agonists) produce bronchodilation and can be used to prevent or inhibit airway obstruction in bronchospastic diseases.22,99... 

In the respiratory tract, ipratropium s is a useful bronchodilator in chronic obstructive pulmonary disease and acute asthma. 

A number of patients who have persistent airflow obstruction exhibit considerable variation in airways resistance and hence in their benefit from bronchodilators drugs for asthma. It is important to recognise the coexistence of asthma with chronic obstructive pulmonary disease in some patients, and to assess their responses to bronchodilators or glucocorticoids over a period of time (as formal tests of respiratory function may not reliably predict clinical response in this setting). 

Salmeterol 42 micrograms bd has been compared with inhaled ipratropium bromide 36 micrograms/day and inhaled placebo in a randomized, double-blind study for 12 weeks in 405 patients with chronic obstructive pulmonary disease (6). Both salmeterol and ipratropium bromide significantly increased the peak expiratory flow rate compared with placebo. Non-specific ear, nose, and throat symptoms (for example sore throat and upper respiratory tract infections) were more common with salmeterol and ipratropium than placebo. There were no significant differences between the groups in the total number of ventricular and supraventricular extra beats. There was no tolerance to the bronchodilating effects of salmeterol. 

Chronic obstructive pulmonary disease is a respiratory condition characterized by irreversible airway obstruction caused by chronic bronchitis or emphysema. The major symptoms of COPD include chronic cough, increased sputum production, and dyspnea. The vast majority of patients with COPD are those who are current or former heavy smokers. Other risk factors for the development of COPD include occupational exposure (dusts, chemicals) and rare genetic disorders (a -antitrypsin deficiency). The medical management of COPD includes pharmacotherapy (bronchodilators, corticosteroids, and antibiotics) in combination with interventions to reduce risk factors for disease progression (e.g., smoking cessation). Some patients require long-term administration of supplemental oxygen. 

Respiratory syncytial virus is the most common cause of acute bronchiolitis, an infection that mostly affects infants during their first year of life. In the well infant, bronchiolitis is usually a self-limiting viral illness, whereas in the child with underlying respiratory or cardiac disease or both, the child may develop severe respiratory compromise (failure) necessitating in-hospital treatment, such as rehydration, oxygen, and in select patients, bronchodilators, ribavirin aerosol, or both. 

Perhaps because protocols are often complex, it is a common experience that some patients get included in trials who shouldn t be. For example, in a trial in asthma, patients might be required to be aged 18 to 65, with an FEVj which is 50-80% of that predicted by the patient s height age and sex, to be capable of showing a 15% improvement above baseline FEV when given a bronchodilator, to be taking no concomitant medication, to have a normal EGG and no history of heart disease and not to have had any incident of respiratory infection within the last month and so forth. It may well be, however, that when the statistician comes to look at the results, one or other of these criteria will have been violated for some patients. 

---