Clinical Pharmacology and Therapeutics

CHAPTER 33
THERAPY OF ASTHMA, CHRONIC
OBSTRUCTIVE PULMONARY DISEASE
(COPD) AND OTHER RESPIRATORY
DISORDERS
● Pathophysiology of asthma 233
● Management of acute severe asthma 233
● Chronic asthma 234
● Acute bronchitis 235
● Chronic bronchitis and emphysema 235
● Drugs used to treat asthma and chronic
obstructive pulmonary disease 236
● Respiratory failure 241
● Cough 242
● α 1 -Antitrypsin deficiency 242
● Drug-induced pulmonary disease 243
PATHOPHYSIOLOGY OF ASTHMA
Asthma is characterized by fluctuating airways obstruction,
with diurnal variation and nocturnal exacerbations. This manifests
as the triad of wheeze, cough and breathlessness. These
symptoms are due to a combination of constriction of bronchial
smooth muscle, oedema of the mucosa lining the small bronchi,
and plugging of the bronchial lumen with viscous mucus and
inflammatory cells (Figure 33.1). Asthma is broadly categorized
into non-allergic and allergic, but there is considerable overlap.
In allergic asthma, which is usually of early onset, extrinsic
allergens produce a type I allergic reaction in atopic subjects.
Type I reactions are triggered via reaginic antibodies (IgE) on
the surface of mast cells and other immune effector cells, especially
activated Th2 lymphocytes, which release cytokines that
recruit eosinophils and promote further IgE synthesis and sensitivity.
Patients with non-allergic (late-onset) asthma do not
appear to be sensitive to any single well-defined antigen,
although infection (usually viral) often precipitates an attack.
Inflammatory mediators implicated in asthma include histamine,
several leukotrienes (LTC 4 /D 4 and E 4 ) 5-hydroxytryptamine
(serotonin), prostaglandin D 2 , platelet-activating factor
(PAF), neuropeptides and tachykinins. Increased parasympathetic
tone due to local and centrally mediated stimuli also promotes
bronchoconstriction.
MANAGEMENT OF ACUTE SEVERE ASTHMA
The proposed management is based on the British Thoracic
Society guidelines and involves the following:
• assessment of asthma severity (e.g. unable to complete
sentences in one breath, pulse rate and pulsus paradox, if
measurable, respiratory rate, breath sounds peak
expiratory flow rate, pulse oximetry and blood gases if
arterial O 2 saturation 92%) to define the need for
hospitalization. Life-threatening asthma (e.g. silent chest,
exhaustion, cyanosis, peak flow 33% of predicted or
best, saturation 92%) needs urgent treatment with:
• high flow oxygen (FiO 2 40–60% oxygen);
• glucocorticosteroids: hydrocortisone i.v., followed by
prednisolone p.o.;
• nebulized β 2 -agonist (e.g. salbutamol) plus ipratropium;
via oxygen-driven nebulizer;
• if the response to the above bronchodilator treatment is
inadequate or not sustained, consider intravenous
bronchodilator: β 2 -agonist (e.g. salbutamol by i.v.
infusion), or aminophylline/theophylline (by slow i.v.
injection);
• in refractory cases, consider magnesium sulphate (slow
i.v. injection/short infusion);