Drug therapy in COPD
Stepwise management of COPD requires bronchodilator therapy as outlined by the NICE guidance document NICE CG115.
Breathlessness and exercise limitation is managed with a short-acting ß2 agonist or muscarinic antagonist when required.
A long-acting ß2 agonist such as salmeterol or formoterol, or muscarinic antagonist such as tiotropium is added during exacerbations or to manage persistent breathlessness, often in combination with an inhaled corticosteroid. Patients who are prescribed a long acting muscarinic antagonist (LAMA) should have their short acting muscarinic antagonist discontinued.
Persistent exacerbations or breathlessness will require combinations of the above.
Antimuscarinic bronchodilators
Short acting
Inhaled ipratropium is a short-acting muscarinic antagonist (SAMA) used to relieve reversible airways obstruction in mild COPD. Maximal bronchodilation is achieved within 30-60 minutes and its maximal duration of action of six hours requires thrice daily dosing to maintain effect.3
Long acting
Tiotropium, glycopyrronium bromide and umeclidinium bromide are long-acting muscarinic antagonists (LAMA) that are indicated for maintenance therapy in COPD. A long duration of action only requires once daily administration but means they cannot be used for relief of acute bronchospasm.
Aclidinium is also a LAMA with a slightly shorter duration of action requiring twice daily administration.
Antimuscarinics should be used with caution in patients with prostatic hyperplasia, bladder obstruction and glaucoma. Particular care needs to be taken to ensure nebulised drug or drug powder does not come into contact with patients' eyes as this can trigger closed angle glaucoma.
The main side effect of antimuscarinic drugs is a dry mouth which should be initially controlled with simple measures such as frequent sips of water, sucking ice cubes or chewing sugar free chewing gum. Other side effects include headache, dizziness, nausea, throat irritation and gastro-intestinal disorders such as constipation, diarrhoea and vomiting. Some tolerance to the side effects should develop.
Long-acting ß2 agonists
Indacaterol and olodaterol are long acting beta2 agonists (LABA) indicated only as maintenance treatment for COPD. They should not be used for relief of acute bronchospasm. Both drugs are administered once daily. Indacaterol is presented as a hard capsule and delivered via a dry powder inhaler whilst olodaterol is available as a solution for inhalation.
Formoterol and salmeterol are also indicated in COPD as twice daily administration and may be more commonly prescribed.
Typical side effects can indicate excessive dosage and include fine tremor, nervous tension, headache and muscle cramps. Potentially serious hypokalaemia can develop, particularly in combination with theophylline, loop diuretics, or corticosteroids.
Similar counselling principles and adherence problems will apply to the use of bronchodilator inhalers whether used for asthma or COPD.
Inhaled corticosteroids (ICS)
Patients who have a FEV1 below 50% of predicted value can be offered an inhaled corticosteroid in conjunction with a LABA as a combination inhaler. Inhaled corticosteroids are glucocorticoids. They have four main effects on the lungs:
- Anti-inflammatory by blocking the action of the inflammatory mediators.
- Immunosuppressive by suppressing hypersensitivity reactions.
- Anti-proliferative by inhibiting synthesis of DNA and cell turnover.
- Vasoconstrictive effects by inhibition of histamine and other vasoconstrictive mediators.
These drugs act on the airways to reduce inflammation, oedema, and mucus secretion. Delivery of the drugs directly to the lungs results in fewer systemic effects than oral corticosteroids, but pharmacists should ensure that patients prescribed high dose inhaled corticosteroids (more than 800mcg beclometasone dipropionate or equivalent daily) receive a steroid warning card.
Typical side effects associated with ICS include oral candidiasis, sore mouth and hoarseness although the incidence of these can be reduced by the patient having a drink after using their inhaler.
A rare and usually mild side effect is paradoxical bronchospasm, this can be prevented by changing from an aerosol to a dry powder inhaler.
The incidence of adverse effects can be reduced by using the lowest possible dose to control symptoms.
Methylxanthines
Theophylline and aminophylline are both xanthines used in the treatment of stable COPD. Their use is recommended in patients who are still symptomatic after using short acting and long acting bronchodilators, with or without corticosteroids, or for patients who are unable to use inhalers correctly.
Xanthines have a bronchodilator effect and are generally not effective in treating exacerbations of COPD. The rate of absorption from modified release theophylline and aminophylline can vary between brands and it is recommended that these drugs are not prescribed generically.
The therapeutic window for theophylline is narrow and plasma concentrations should be monitored. The plasma concentration is reduced in smokers, and drug levels should be monitored carefully if patients stop smoking, and their doses adjusted if necessary.
The most common side effect associated with xanthines is nausea, other side effects include vomiting, tremor, headache, CNS stimulation, insomnia, palpitations and arrhythmias. Care should be taken when first dispensing xanthines due to the significant number of potential drug interactions.
Other treatments
Mucolytics, e.g. carbocisteine and erdosteine break down sputum making it less thick and sticky and therefore easier to remove by coughing. They do not stop the cough but they should make it easier to cough and remove phlegm. They may also reduce the number of flare-ups by making it harder for bacteria to cause an infection.
Some hospitals run pulmonary rehabilitation courses involving exercise and education, these aim to improve the patient’s mobility, health and quality of life.
If the patient has low levels of oxygen in the blood they may require domiciliary oxygen supplies. Oxygen is given for around 15-20 hours each day via a face mask. It is highly flammable so should not be considered if the patient still smokes.