Pharmacological therapy

Aids to smoking cessation

Smokers should be strongly encouraged to stop; smoking cessation advice and support, together with various pharmaceutical products are available for those who wish to do so. Nicotine replacement allows some individuals to ease the effects of tobacco withdrawal. Nicotine can be administered in various forms, including lozenges, gum, transcutaneous patches and by inhalation. Pharmaceutical agents with demonstrable benefits in selected individuals include bupropion, originally an antidepressant, and varencicline, a selective nicotine receptor agonist.

Bronchodilators

Bronchodilators vary in both their mode and duration of action and they can be administered by various routes. The commonly used inhaled bronchodilators are listed in table 1. All are aimed essentially at relaxing the smooth muscle of the airway wall and they are very widely used, both in adults and children, either as sole or adjunctive treatment for asthma and chronic obstructive pulmonary disease (COPD), and for other conditions characterised by diffuse airway narrowing, e.g. bronchiectasis.

Among the most frequently used bronchodilators are the β-sympathomimetic agonists, which mimic the action of the sympathetic nervous system by selectively stimulating the β2receptors on bronchial smooth muscle. They are most commonly administered via inhalation, traditionally from a metered-dose inhaler (MDI). However, careful attention to inhaler technique is important, as many individuals experience difficulty in coordinating the manoeuvres necessary for effective inhalation with the traditional ‘press and breathe’ inhaler. Detailed guidance on the available inhaler devices and their use has recently been published by a task force set up jointly by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM). Devices used to overcome problems with inhaler technique include inhalation via a ‘spacer’ (figure 1a) and breath-activated inhalers (figure 1b). Alternatively, the drug can be inhaled as a very fine dry powder (dry powder inhaler (DPI)) (figure 1c) or as a soft mist (soft mist inhaler (SMI)) (figure 1d). Sometimes (during an acute asthma attack, for example) larger doses are inhaled as a nebulised solution driven by a flow of air or oxygen (usually available only in hospital) or by a portable, electrically powered compressor (figure 1e).

Short-acting β2-agonists are a mainstay of treatment for symptomatic relief and for acute exacerbations of asthma and COPD, while longer-acting agents are used on a regular basis to produce background bronchodilatation in patients with chronic airway obstruction, usually in conjunction with an inhaled steroid (table 1).

Anti-muscarinic drugs inhibit the action of the parasympathetic nervous system and produce bronchodilatation by reducing the tone of the airway smooth muscle; as with β 2 -agonists (together with which they are often used), both short- and long-acting versions are available. Administration is by inhalation, which avoids the side-effects of widespread parasympathetic inhibition.

The methylxanthine bronchodilator drug theophylline is a nonspecific inhibitor of the enzyme phosphodiesterase (PDE). It is administered orally; its more soluble derivative, aminophylline, is given intravenously and has been a traditional method of treating acute asthma attacks. Theophylline is, however, less favoured nowadays as side-effects are frequent and blood level monitoring is desirable for control of the appropriate dose. More recently developed, specific PDE inhibitors include the PDE4 inhibitors (e.g. roflumilast) which have bronchodilator and anti-inflammatory effects in COPD and the PDE 5 inhibitors (e.g . sildenafil) used in the treatment of pulmonary hypertension.

Corticosteroids

Corticosteroids, such as prednisolone (given orally) or methyl prednisolone (given parenterally), are powerful anti-inflammatory agents used in a wide range of medical conditions. In respiratory practice, steroids are used most commonly by inhalation in the long-term treatment of asthma and COPD. Oral or intravenous steroids are the mainstay of treatment of acute asthma; in most cases, regular treatment for 5–10 days suffices and a similar approach has been shown to hasten recovery in acute exacerbations of COPD.

When introduced in the 1970s, inhaled steroids revolutionised the long-term treatment of asthma, as they allowed better control of the condition without the side-effects of oral steroids, which had been widely used previously. Though  less effective than in asthma, regular inhaled corticosteroid treatment has also been shown to benefit patients with severe COPD, by reducing the frequency of exacerbations. An inhaled steroid is usually administered twice daily from an MDI or DPI and, increasingly, a steroid is combined with a long-acting β2-agonist in the same inhaler (table 1).

Category Duration of action Generic name Proprietary name (manufacturer)
β2-agonist Short Salbutamol Ventolin (GSK), Airomir (Graceway Pharmaceuticals)
    Terbutaline Bricanyl (AstraZeneca)
  Long Salmeterol Serevent (GSK)
    Formoterol Oxis (AstraZeneca), Foradil (Schering Plough and Novartis), Atimos (Chiesi)
    Indicaterol Onbrez (Novartis)
Antimuscarinic Short Ipratropium Atrovent (Boehringer Ingelheim)
  Long Tiotropium Spiriva (Boehringer Ingelheim and Pfizer)
Corticosteroid   Beclomethasone Becotide (GSK), Qvar (Teva), Clenil (Chiesi)
    Budesonide Pulmicort (AstraZeneca)
    Fluticasone Flixotide (GSK)
    Mometasone Asmanex (Merck, Sharpe and Dohme)
    Ciclesonide Alvesco (Takeda)
Compound preparations   Salmeterol+fluticasone Seretide (GSK)
    Formoterol+budesonide Symbicort (AstraZeneca)
Table 1 – Commonly used inhaled therapy for asthma and chronic obstructive pulmonary disease.

Oral steroids are also used for the longer-term treatment of some types of interstitial lung disease, particularly sarcoidosis, hypersensitivity pneumonitis and some of the interstitial pneumonias. Long-term oral steroid treatment is, however, accompanied by frequent side-effects, against which the benefit of suppressing troublesome symptoms (usually breathlessness) has to be balanced.

Antibiotics

For respiratory infections, antibiotics can be given either as a short course (5–10 days for acute infective exacerbations of COPD, for example) or on a longer-term basis, particularly for chronic bronchial infection (in cystic fibrosis (CF) or non-CF bronchiectasis, for instance).

Ideally, antibiotic treatment is tailored to the specific infecting organism(s), but often, especially in COPD, this may not be apparent or may come to light only after a couple of days when culture results become available; consequently, a broad-spectrum antibiotic is usually prescribed in order to cover the most likely pathogens. Most infective exacerbations of COPD are due initially to viral infection, which is not generally susceptible to conventional antibiotics; however, this is often superseded by bacterial infection, at which stage the sputum becomes purulent and an antibiotic is indicated.

In nonimmunocompromised patients, less severe community-acquired pneumonia usually responds to a broad-spectrum antibiotic, e.g. one of the β-lactam (penicillin) family. However, combinations of antibiotics are used when pneumonia is more severe and specifically targeted treatment is desirable when the infecting agent is likely to be less susceptible to the commonly used broad-spectrum agents, for instance Mycoplasma pneumoniae, Staphylococcus aureus or Legionella pneumophila (Legionnaires’ disease).

With chronic bronchial infection, as in CF or bronchiectasis, longer-term antibiotic treatment may be indicated, particularly to control pathogens such as Pseudomonas aeruginosa; some, such as tobramycin, can be given effectively as an aerosol by nebulisation.

The treatment of tuberculosis (TB) and related mycobacterial infections requires specific antibiotics, which are given in combination for a prolonged period (at least 6 months for TB and up to 24 months for non-tuberculous mycobacteria). The most frequently used combination for TB comprises isoniazid plus rifampicin for 6 months, supplemented by pyrazinamide and ethambutol for the first 2 months. Identifying the drug sensitivity of the infecting organism is particularly important due to the increasing frequency of drug-resistant strains.

Other drugs

Diuretics

Diuretics are frequently used in patients with chronic fluid retention (‘cor pulmonale’) due to severe pulmonary hypertension, either primary or secondary to advanced COPD.

Anticoagulation and thrombolytic agents

Anticoagulation is the usual primary treatment in acute pulmonary embolism, with thrombolytic agents used if embolism is sufficiently extensive to compromise cardiac output.

Vasodilators

Specific vasodilator and other drugs are increasingly used to improve the pulmonary circulation in patients with primary pulmonary hypertension.

Mucolytic drugs

Mucolytic drugs, such as carbocisteine and dornase alpha (DNAse) reduce the viscosity (‘stickiness’) of sputum and aid expectoration, e.g. in CF, where they may reduce the frequency of acute exacerbations. Mucolytic drugs may also reduce the frequency of exacerbations in COPD.

Cytotoxic drugs

Cytotoxic drugs are used in the treatment of lung cancer and mesothelioma. Although not likely to be curative, some agents, usually in combination, prolong average life-expectancy in small cell lung cancer and they are increasingly used as palliative treatment of nonsmall cell lung cancer.

Some cytotoxic drugs are also useful in the treatment of certain types of interstitial diseases and pulmonary vasculitis; for example, cyclophosphamide in granulomatosis with polyangiitis (Wegener’s).

Tumour growth modifiers

Biological therapy with drugs such as those that inhibit the enzyme tyrosine kinase is effective against cancers that express certain genes (e.g. the epidermal growth factor receptor); this type of ‘tailored’ approach to certain lung cancers offers hope for greater therapeutic success in future.

Comorbidity

Many patients with respiratory disease also require medication for comorbid disease: for instance, in cases of coexisting ischaemic heart disease and COPD, which are common comorbidities due to their shared smoking aetiology.

See the entire Principles of respiratory therapy Chapter