872
P A R T 1 0
Drugs acting on the respiratory system
Salbutamol, the prototype drug, is the drug of
choice in adults and children for the treatment of acute
bronchospasm, including that caused by anaphylaxis;
it is also available for inhalation. Because adrenaline is
associated with systemic sympathomimetic effects, it is
not the drug of choice for people with cardiac condi-
tions. See Table 55.1 for usual indications for each of
these agents.
Pharmacokinetics
Sympathomimetics available only as inhalants include
eformoterol, indacaterol and salmeterol.
Other sympathomimetics are available in various
forms. Terbutaline and salbutamol can be used as inhal-
ants and as oral and parenteral agents.
These drugs are rapidly distributed after injection;
they are transformed in the liver to metabolites that
are excreted in the urine. The half-life of these drugs is
relatively short—less than 1 hour except for indacaterol
whose half-life is 49 hours. They are known to cross the
placenta and to enter breast milk (see Contraindications
and cautions). The inhaled drugs are rapidly absorbed
into the lung tissue. Although very little of the drug is
absorbed systemically, any absorbed drug will still be
metabolised in the liver and excreted in urine. Indaca-
terol, however, is eliminated predominantly (~90%)
through the fecal route. About 54% of the drug is elim-
inated unchanged, and ~23% is excreted as hydoxylated
indacaterol metabolite.
Contraindications and cautions
These drugs are contraindicated or should be used with
caution, depending on the severity of the underlying
condition,
in conditions that would be aggravated by
the sympathetic stimulation
,
including cardiac disease,
vascular disease, arrhythmias, diabetes and hyper
thyroidism. Indacaterol is indicated for people with
COPD and not for people with asthma. Indacaterol
should not be used for treatment of acute symptoms
of COPD or administered more than once a day. Inda-
caterol should not be administered with other LABAs.
These drugs should be used during pregnancy and
breastfeeding only if the benefits to the mother clearly
outweigh potential risks to the fetus or neonate.
Adverse effects
Adverse effects of these drugs, which can be attributed to
sympathomimetic stimulation, include CNS stimulation,
GI upset, cardiac arrhythmias, hypertension, broncho
spasm, sweating, pallor and flushing. If the person is
taking eformoterol for asthma maintenance, additional
doses of drug should not be used for exercise-induced
asthma because the cumulative sympathomimetic effects
can cause serious cardiovascular problems.
Clinically important drug–drug interactions
Special precautions should be taken to avoid the com-
bination of sympathomimetic bronchodilators with
the general anaesthetics cyclopropane and halogen-
ated hydrocarbons. Because these drugs sensitise the
myocardium to catecholamines, serious cardiac compli-
cations could occur. The therapeutic effect of indacaterol
is blocked with the concomitant use of ß-blockers.
Hypokalemic effects of indacaterol may be potenti-
ated in individuals using diuretics, steroids or xanthine
derivatives.
Prototype summary: Adrenaline
Indications:
Treatment of anaphylactic reactions,
acute asthmatic attacks; relief from respiratory
distress of COPD and bronchial asthma.
Actions:
Reacts at
α
- and
β
-receptor sites in
the sympathetic nervous system to cause
bronchodilation, increased heart rate, increased
respiratory rate and increased blood pressure.
Pharmacokinetics:
Route
Onset
Peak
Duration
SC
5–10 mins 20 mins 20–30 mins
IM 5–10 mins 20 mins 20–30 mins
IV
Instant
20 mins 20–30 mins
Inhalation 3–5 mins 20 mins 1–3 hours
T
1/2
:
Unknown; metabolised by normal neural
pathways.
Adverse effects:
Fear, anxiety, restlessness, headache,
nausea, decreased renal formation, pallor,
palpitation, tachycardia, local burning and stinging,
rebound congestion with nasal inhalation.
Care considerations for
people receiving sympathomimetics
Assessment: History and examination
■
■
Assess for
possible contraindications or cautions
:
any known allergies to any sympathomimetic or
drug vehicle
to prevent hypersensitivity reactions
;
cigarette use,
which affects the metabolism of
the drug
;
pregnancy or breastfeeding,
which
require cautious use of the drug
; cardiac disease,
vascular disease, arrhythmias, diabetes and
hyperthyroidism,
which may be exacerbated by
sympathomimetic effects
; and use of the general
anaesthetics cyclopropane and halogenated
hydrocarbons,
which sensitise the myocardium to
catecholamines and could cause serious cardiac
complications if used with these drugs.
