Page 375 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 20 Drugs Used in Asthma 361

in that it is also characterized by airflow limitation, although the heightened risk of bacterial pneumonia. Its use is thus recom-
obstruction of COPD is not fully reversible with treatment. The mended only for patients with severe airflow obstruction or with
airflow limitation of COPD, believed to reflect an abnormal inflam- a history of prior exacerbations.
matory response of the lung to noxious particles or gases, especially
to cigarette smoke, absolutely progresses if the exposure continues COPD Exacerbations
and appears to progress, albeit more slowly, even if the exposure
ceases. The belief that COPD develops in only 15–30% of habitual Acute exacerbations of COPD are a major driver of the morbid-
smokers is now challenged by radiographic demonstration of ity, mortality, and health care costs of COPD. Because of the
important, progressive changes in bronchial wall thickness and loss greater age of the patients affected and the prevalence of comor-
of lung tissue even in smokers with measures of pulmonary function bidities, especially cardiovascular disease, the mortality of acute
in the normal range. Although COPD differs from asthma, many exacerbations is greater than that of exacerbation of asthma, but
of the same drugs are used in its treatment. This section discusses management does not differ greatly except in the routine use of
the drugs that are useful in both conditions; a more comprehensive antibiotics, which are given because exacerbations of COPD fre-
guide to their use is available in the Global Initiative for Chronic quently involve bacterial infection of the lower airways.
Obstructive Lung Disease (GOLD) guidelines for classification and Because of their importance in driving the morbidity and
treatment of COPD (http://goldcopd.org). mortality of COPD, much attention has been paid to approaches
Although asthma and COPD are both characterized by airway to prevention of COPD exacerbations. For patients with a his-
inflammation, reduction in maximum expiratory flow, and epi- tory of two or more exacerbations, daily treatment with an
sodic exacerbations of airflow obstruction, most often triggered by ICS is appropriate, and a recent large study showed significant
viral respiratory infection, they differ in many important respects. reduction in exacerbation frequency from daily treatment with
Compared to asthma, COPD occurs in older patients, is associ- azithromycin. An innovative, although initially counterintui-
ated with neutrophilic rather than eosinophilic inflammation, is tive, hypothesis is now also under examination: that treatment
poorly responsive even to high-dose ICS therapy, and is associated with the selective β -receptor antagonist, metoprolol succinate,
1
with progressive, inexorable loss of pulmonary function over time, will reduce exacerbations in patients with moderate to severe
especially with continued cigarette smoking. COPD. The hypothesis is counterintuitive because nonselective
Despite these differences, the approaches to treatment are simi- β-blocker therapy so predictably worsens airflow obstruction
lar, although the benefits expected (and achieved) are less for COPD in asthmatic patients that it has long been considered contra-
than for asthma. For relief of acute symptoms, inhalation of a indicated for patients with COPD. Several developments and
short-acting β agonist (eg, albuterol), of an anticholinergic drug (eg, observations have changed this view. These include the devel-
ipratropium bromide), or of the two in combination is usually effec- opment of selective β -receptor antagonists and the recogni-
1
tive. For patients with persistent symptoms of exertional dyspnea tion that the use of β-blocking agents—once also considered
and limitation of activities, regular use of a long-acting bronchodila- contraindicated for acute myocardial infarction and congestive
tor, whether an LABA or a long-acting anticholinergic, or the two heart failure—reduces mortality from these conditions. Epide-
together, is indicated. Theophylline may have a particular place in miologic surveys show significant reductions in overall mortal-
the treatment of COPD, as it may improve contractile function of ity and exacerbations in COPD patients taking a β-receptor
the diaphragm, thus improving ventilatory capacity. The nonmeth- antagonist. Whether these effects reflect the therapeutic effect of
ylxanthine, roflumilast, a selective phosphodiesterase inhibitor that β-blockers on mortality from coincident cardiovascular disease
improves pulmonary function and reduces exacerbation frequency, or reflect some direct effect on airway function is unknown, but
is now approved as a treatment for COPD. the hypothesis is currently under study in a large, prospective,
The place of ICS therapy is less central to treatment of COPD placebo-controlled study of metoprolol treatment of COPD
than of asthma, in part because of its lower efficacy for this condi- patients at risk for exacerbations (https://clinicaltrials.gov/ct2/
tion and in part because of reports of its use being associated with show/NCT02587351).