Clinical Pharmacology and Therapeutics

234 THERAPY OF ASTHMA, COPD AND OTHER RESPIRATORY DISORDERS
Cromoglicate
Nedocromil
ve
2 -Agonists
Antimuscarinics
Theophylline
Smooth muscle
contraction
Inhibitory
effects
Stimulatory
effects
Omalizumab
ve
IgE
IgE
ve
ve
ve
Bronchial
smooth muscle
IgE
IgE
Mediator
cell
IgE
Histamine, LT, PGs, PAF, adenosine
IgE production
Episodic
wheeze
Allergic
stimulus
IgE
ve
Interleukin-4
B
cell
ve
T
cell
Interleukin-5
Eosino–
phil
PAF, LTS
Basic
proteins
Chronic
symptoms
ve
ve
ve
Wheeze
Bronchial
hyper-responsiveness
Leukotriene
modulators
ve
Glucocorticosteroids
ve
Inflammatory
mucus plug
Figure 33.1: Pathophysiology of asthma and sites of drug action. PAF, platelet-activating factor; LTs, leukotrienes; PGs, prostaglandins.
• an antibiotic (e.g. co-amoxiclav or clarithromycin), if
bacterial infection is strongly suspected – beware potential
interactions with theophylline, see below;
• if the patient fails to respond and develops increasing
tachycardia, with increasing respiratory rate and a fall in
PaO 2 to 8 kPa or a rise in PaCO 2 to 6 kPa, assisted
ventilation will probably be needed;
• sedation is absolutely contraindicated, except with
assisted ventilation.
• general care: monitor fluid/electrolyte status (especially
hypokalaemia) and correct if necessary.
CHRONIC ASTHMA
The primary objectives of the pharmacological management of
chronic asthma are to obtain full symptom control, prevent exacerbations
and achieve the best possible pulmonary function,
with minimal side effects. The British Thoracic Society/Scottish
Intercollegiate Guideline Network (BTS/SIGN) have proposed
a five-step management plan, with initiation of therapy based
on the assessed severity of the disease at that timepoint. Figure
33.2 details the treatment in the recommended steps in adult
asthmatics. Step 1 is for mild asthmatics with intermittent symptoms
occurring only once or twice a week; step 2 is for patients
with more symptoms (more than three episodes of asthma symptoms
per week or nocturnal symptoms). Step 3 is for patients
who have continuing symptoms despite step 2 treatment and
steps 4 and 5 are for more chronically symptomatic patients or
patients with worsening symptoms, despite step 3 or 4 treatment.
PRINCIPLES OF DRUG USE IN TREATING
CHRONIC ASTHMA
1. Metered dose inhalers (MDIs) of β 2 -agonists are
convenient and with correct usage little drug enters the
systemic circulation. Aerosols are particularly useful for
treating an acute episode of breathlessness. Long-acting
β 2 -agonist (e.g. salmeterol) should be taken regularly with
top-ups of ‘on-demand’ shorter-acting agents. Oral
preparations have a role in young children who cannot
co-ordinate inhalation with activation of a metered-dose
inhaler. Children over five years can use inhaled drugs
with a ‘spacer’ device. There are several alternative
approaches, including breath-activated devices and
devices that administer the dose in the form of a dry
powder that is sucked into the airways.
2. Patients should contact their physician promptly if their
clinical state deteriorates or their β 2 -agonist use is increasing.
3. Inhaled glucocorticosteroids (e.g. beclometasone,
fluticasone, budesonide) are initiated when symptoms
are not controlled or when:
• regular (rather than occasional, as needed) doses
of short-acting β 2 -agonist bronchodilator are
required;
• repeated attacks interfere with work or school.
Adverse effects are minimized by using the inhaled route.
Severely affected patients require oral glucocorticosteroids
(e.g. prednisolone).