A hundred years ago the main treatments for obstructive lung disease were adrenal gland extracts, herbally-derived sympathomimetic ephedrine and anticholinergics, such as atropine. There have been extraordinary advancers in the pharmacological therapy of asthma and COPD, yet the major classes of therapy we use today are based on these original therapies – long-acting β<sub>2</sub>-agonists (LABA) derived from adrenaline and muscarinic receptor antagonists (LAMA) and inhaled corticosteroids (ICS) developed from the adrenal cortex hormone cortisol. Triple fixed-dose inhalers containing all 3 drugs have now been developed and are convenient for some patients. In asthma, by far the greatest advance has been the Introduction of ICS for control of the underlying eosinophilic inflammation of the airways. Although ICS are effective in most patients, there is often very poor adherence as symptoms are intermittent. In a new strategy, instead of a short-acting β<sub>2</sub>-agonist, such as salbutamol, patients use a reliever inhaler containing a rapidly-acting LABA formoterol combined with an ICS. This provides much better control of asthma and is a simple strategy for most patients. At the other end of the spectrum, patients with eosinophilic severe asthma not controlled on conventional therapies may now be controlled with biologics, which include antibodies against immunoglobulin-E, interleukin-5 and interleukin-4 receptor. In COPD the mainstay of treatment is LABA and LAMA, often as a combination inhaler, whereas ICS are only effective in a proportion of patients that also have eosinophilic inflammation. New safe anti-inflammatory treatments are needed to prevent the progression and exacerbations of COPD.
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The effects of nifedipine, a potent calcium antagonist, were studied in patients with unstable angina, coronary spasm and myocardial ischemia. Data from two separate groups of patients studied in the cardiac catheterization laboratory indicate that intracoronary injection of nifedipine promptly reversed coronary spasm—whether provoked or spontaneous—in five of six patients. In other patients, direct intracoronary injection of the drug was compared with intravenous administration. After intracoronary injection, local mechanical cardiac action virtually ceased, and the ventricular wall became thinner during systole. Thus, a specific inhibitory action on contractile energy expenditure could be demonstrated in the presence of increased coronary flow. This “oxygen-sparing” effect was tested in a group of 31 patients with symptomatic unstable angina whose pain at rest, with ST-T changes, had not responded to 8 hours of treatment with maximal beta adrenergic blockade, nitrates and bed rest. The addition of 6 × 10 mg of nifedipine rendered 27 of these patients asymptomatic within 1.5 hours. In the four patients who did not respond, coronary arteriography demonstrated severely stenotic lesions. Two of the four patients subsequently responded to intraaortlc balloon pumping and bypass surgery; one patient had a myocardial infarction and one who had a 90 percent reduction in the diameter of the left main coronary artery, died. It is concluded that nifedipine should be added to beta adrenergic blockade therapy if the latter does not appear to be immediately effective. This combination has not been shown to cause any hemodynamlc deterioration, and only a minority of the patients treated sustained a myocardial infarction during the first 3 months of follow-up. The use of nifedipine in unstable angina deserves further clinical evaluation.
<b>Background:</b> Theophylline can still have a role in the management of stable COPD but its use remains controversial mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile with respect to theophylline. <b>Aim:</b> We have carry out a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD. <b>Methods:</b> A network meta-analysis on xanthines (aminophylline, bamiphylline, doxofylline, enprophylline, theophylline) and COPD was carried out in agreement with PRISMA and PROSPERO. The primary endpoints were the impact of xanthines on the lung function and the risk of adverse events (AEs), via normalizing data on safety as a function of person-week. Data obtained from 1158 COPD patients were selected from 16 studies and analyzed by using a full Bayesian approach. <b>Results:</b> The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 second [FEV1]) and safety (risk of AEs) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety) (Figure 1). <b>Conclusions:</b> The overall efficacy/safety analysis suggests that doxofylline seems to be the best xanthine for the treatment of COPD.
Calcium has a central role coupling stimulus to cellular activities such as secretion and contraction. Because calcium is critical for airway smooth muscle contraction, degranulation of mast cells and secretion of mucus, there has been great interest and hope in the use of calcium channel blockers in the treatment of asthma. We here discuss the effects of calcium channel blockers and also review clinical studies of these drugs in asthma, focusing on recent findings. There have been several recent reviews on this topic (1,2) and it is now possible to evaluate the role of these drugs in the management of asthma.
