A Textbook of Clinical Pharmacology and Therapeutics

sufficient to cause expectoration. At this stage, there need be
no disability and measures such as giving up smoking (which
may be aided by the use of nicotine replacment; see Chapter
53) and avoidance of air pollution improve the prognosis.
Simple hypersecretion may be complicated by infection or the
development of airways obstruction. Bacterial infection is
usually due to mixed infections including organisms such as
Haemophilus influenzae, although pneumococci, staphylococci
or occasionally Branhamellamay also be responsible. The com-
monly encountered acute bronchitic exacerbation is due to
bacterial infection in only about one-third of cases. In the rest,
other factors – such as increased air pollution, environmental
temperature changes or viruses – are presumably responsible.
Mycoplasma pneumoniaeinfections may be responsible for
some cases and these respond to macrolides. Antibiotic ther-
apy is considered when there is increased breathlessness,
increased sputum volume and, in particular, increased spu-
tum purulence. Rational antibiotic choice is based on ade-
quate sputum penetration and the suspected organisms. The
decision is seldom assisted by sputum culture or Gram stain,
in contrast to the treatment of pneumonia. It is appropriate to
vary the antibiotic used for different attacks, since effective-
ness presumably reflects the sensitivity of organisms resident
in the respiratory tract. Commonly used antibacterials
include:

• azithromycinorclarithromycin;


• amoxicillinorco-amoxiclav;


• oral cephalosporin, e.g. cefadroxil;


• fluoroquinolone, e.g. ciprofloxacin.

Prevention of acute exacerbations is difficult. Stopping smok-
ing is beneficial. Patients are often given a supply of antibiotic
to take as soon as their sputum becomes purulent. Despite
recovery from an acute attack, patients are at greatly increased
risk of death or serious illness from intercurrent respiratory
infections, and administration of influenza and pneumococcal
vaccines is important. Airways obstruction is invariably pre-
sent in chronic bronchitis, but is of variable severity. In some
patients there is a reversible element, and a formal trial of bron-
chodilators, either β 2 -adrenoceptor agonists or anticholiner-
gics, e.g. ipratropium, is justified to assess benefit. Similarly,
a short therapeutic trial of oral glucocorticosteroids, with
objective monitoring of pulmonary function (FEV 1 /FVC), is
often appropriate. Many patients are not steroid responsive;
approaches designed to reverse glucocorticosteroid resistance,
includingtheophylline, are currently under investigation.
Long-term oxygen therapy (LTOT), usually at least 15 hours
daily, in severely disabled bronchitis patients with pulmonary
hypertension decreases mortality and morbidity. The mortal-
ity of such patients is related to pulmonary hypertension,
which is increased by chronic hypoxia. Relief of hypoxia on a
long-term basis by increasing the concentration of inspired
oxygen reverses the vasoconstriction in the pulmonary arter-
ies and decreases pulmonary hypertension. Long-term oxy-
gen therapy cannot be safely offered to patients who continue
to smoke because of the hazards of fire and explosion.

236 THERAPY OF ASTHMA,COPD AND OTHER RESPIRATORY DISORDERS

Key points

Therapy of chronic obstructive airways disease.

Acute exacerbation

• Controlled oxygen therapy (e.g. FiO 2 24–28%);


• Nebulizedβ 2 -agonists (salbutamolevery 2–4 hours, if
  needed) or intravenously if refractory;


• Nebulized anticholinergics, such as ipratropium bromide;


• Antibiotics (e.g. clarithromycin,co-amoxiclav,
  levofloxacin).


• Short-term oral prednisolone.
  Chronic disease


• Stop smoking cigarettes.


• Optimize inhaled bronchodilators
  (salbutamol/ipratropium bromide) and their
  administration.


• Consider oral theophyllineand/or inhaled
  glucocorticosteroids.


• Treat infection early and aggressively with antibiotics.


• Offer long-term oxygen therapy (LTOT) for at least 15
  hours per day for cor pulmonale.


• Diuretics should be used for peripheral oedema.


• Consider venesection for severe secondary polycythaemia.


• Exercise, within limits of tolerance.

DRUGS USED TO TREAT ASTHMA AND

CHRONIC OBSTRUCTIVE PULMONARY

DISEASE

β 2 -AGONISTS

Use

β 2 -Agonists (e.g. salbutamoland the long-acting β 2 -agonist

salmeterol) are used to treat the symptoms of bronchospasm

in asthma (both in an acute attack and as maintenance ther-

apy) and chronic obstructive pulmonary disease (COPD).

(Intravenoussalbutamolis also used in obstetric practice to

inhibit premature labour). For asthma, β 2 -agonists are given

via inhalation where possible, see also Table 33.1.

1. Inhalation formulations include:
   
   
   • metered-dose inhaler – aerosol. Some patients are
     unable to master this technique;
   
   
   • aerosol administered via a nebulizer;
   
   
   • as a dry powder – almost all patients can use a dry-
     powder inhaler correctly.
     2.Oral formulations, including slow-release preparations.
   
   
   
   

Intravenous administration

The increase in FEV 1 after inhaling salbutamolbegins within

5–15 minutes, peaks at 30–60 minutes and persists for 4–6 hours.

Pharmacological effects, mechanism of action and

adverse effects

Agonists occupying β 2 -adrenoceptors increase cyclic adeno-

sine monophosphate (cAMP) by stimulating adenylyl cyclase

via stimulatory G-proteins. Cyclic AMP phosphorylates a