A Textbook of Clinical Pharmacology and Therapeutics

for many patients. Codeinedepresses the medullary cough

centre and is effective as are pholcodineanddextromethor-

phan, other opioid analogues.

EXPECTORANTS

Difficulty in clearing viscous sputum is often associated with

chronic cough. Various expectorants and mucolytic agents are

available, but they are not very efficacious.

• Mixtures containing a demulcent and an antihistamine, a
  decongestant such as pseudoephedrineand sometimes a
  cough suppressant, such as codeine, are often prescribed.
  This combination is less harmful than anticipated,
  probably because the doses of most of its components are
  too low to exert much of an effect.


• Drugs which reduce the viscosity of sputum by altering the
  nature of its organic components are also available. They are
  sometimes called mucolytics, and the traditional agents are
  unhelpful because they reduce the efficacy of mucociliary
  clearance (which depends on beating cilia being
  mechanically coupled to viscous mucus). The increased
  viscosity of infected sputum is due to nucleic acids rather
  than mucopolysaccharides, and is not affected by drugs
  such as bromhexineoracetyl cysteine, which are therefore
  ineffective. rhDNAase(Pulmozyme)(phosphorylated
  glycosylated recombinant human deoxyribonuclease 1
  enzyme), given by jet nebulizer, cleaves extracellular
  bacterial DNA, is proven effective in cystic fibrosis patients,
  decreasing sputum viscosity and reducing the rate of
  deterioration of lung function. Its major adverse effects are
  pharyngitis, voice changes, rashes and urticaria.

PULMONARY SURFACTANTS

Several pulmonary surfactants are available. Colfosceril palmi-

tate(synthetic dipalmitoyl-phosphatidylcholine with hexade-

canol and tyloxapol) is used in newborn infants undergoing

mechanical ventilation for respiratory distress syndrome (RDS).

It reduces complications, including pneumothorax and bron-

chopulmonary dysplasia, and improves survival. Colfoscerilis

given via the endotracheal tube, repeated after 12 hours if still

intubated. Heart rate and arterial blood oxygenation/satura-

tion must be monitored. The administered surfactant is rapidly

dispersed and undergoes the same recycling as natural surfac-

tant. Its principal adverse effects are obstruction of the endo-

tracheal tubes by mucus, increased incidence of pulmonary

haemorrhage and acute hyperoxaemia due to a rapid improve-

ment in the condition.

1 -ANTITRYPSIN DEFICIENCY

α 1 -Antitrypsin is a serine protease produced by the liver.

It inhibits neutrophil elastase in lungs. In patients with

242 THERAPY OF ASTHMA,COPD AND OTHER RESPIRATORY DISORDERS

further assessment to 35%. If oxygen produces respiratory
depression, assisted ventilation may be needed urgently.

Specific measures

Respiratory failure can be precipitated in chronic bronchitis by
infection, fluid overload (e.g. as the pulmonary artery pres-
sure increases and cor pulmonale supervenes) or bronchocon-
striction. Antibacterial drugs are indicated if the sputum has
become purulent. Bronchospasm may respond to salbutamol
given frequently via nebulizer (often supplemented by nebu-
lizedipratropium).Hydrocortisoneis given intravenously
for 72 hours. If the PaO 2 continues to fall and the PaCO 2 con-
tinues to rise, endotracheal intubation with suction and intermit-
tent mandatory mechanical ventilation should be considered,
especially if consciousness becomes impaired.

Key points

Respiratory failure

• Type I (hypocapnic hypoxaemia) and type II
  (hypercapnic hypoxaemia).


• Therapy for type I is supportive with high-percentage
  oxygen (FiO 2 40–60%).


• Therapy for type II is low-percentage oxygen (FiO 2
  24–28%) and treatment of reversible factors – infection
  and bronchospasm (with antibiotics, bronchodilators
  and glucocorticosteroids).


• Type I or type II respiratory failure may necessitate
  mechanical ventilation.


• Central nervous system (CNS)-depressant drugs (e.g.
  opiates, benzodiazepines) may exacerbate or
  precipitate respiratory failure, usually type II.


• Sedatives are absolutely contraindicated (unless the
  patient is already undergoing mechanical ventilation).

COUGH

COUGH SUPPRESSANTS

Cough is a normal physiological reflex that frees the respira-
tory tract of accumulated secretions and removes particulate
matter. The reflex is usually initiated by irritation of the
mucous membrane of the respiratory tract and is co-ordinated
by a centre in the medulla. Ideally, treatment should not
impair elimination of bronchopulmonary secretions nor a
thorough diagnostic search. A number of antitussive drugs are
available, but critical evaluation of their efficacy is difficult.
Patients with chronic cough are often poor judges of the anti-
tussive effect of drugs. Objective recording methods have
demonstrated dose-dependent antitussive effects for cough
suppressants, such as codeine and dextromethorphan.
However, cough should not be routinely suppressed, because
of its protective function. Exceptions include intractable
cough in carcinoma of the bronchus and cases in which an
unproductive cough interferes with sleep or causes exhaus-
tion. Bland demulcent syrups containing soothing substances
(e.g. menthol or simple linctus BPC) provide adequate comfort