Monograph: |
Isoprenaline sulphate
A white or almost white, odourless or almost odourless, crys-
talline powder. It gradually darkens on exposure to air and
light. Soluble I in 3 of water and I in 50 of alcohol: less sol-
uble in dehydrated alcohol: practically insoluble in chloro-
form. in dichloromethane. and in ether. A 1% solution in
water has a pH of about 5 and a 5% solution has a pH of 4.3
to 5.5. Solutions become pink to brownish-pink on standing
exposed lo air and almost immediately so when made alka-
line. Store in airtight-containers. Protect from light.
Adverse Effects and Precautions
The adverse effects of isoprenaline may include
tachycardia and cardiac arrhythmias, palpitations.
hypotension, tremor, headache, sweating, and facial
flushing. Prolonged use of isoprenaline has been as-
sociated with swelling of the parotid glands. Special
caution is needed in the presence of ischaemic hean
disease, diabetes mellitus. and hyperthyroidism.
Prolonged use of isoprenaline tablets sublingually
has been reported to cause severe damage, to the
teeth due to the acidic nature of the drug. Sublingual
use or inhalation may colour the saliva or sputum
For the adverse effects of sympathomimetics in gen-
eral, and precautions for their use. sec Adrenaline.
Increased mortality. There has been some increased
mortality and morbidity that has been observed in
asthmatic patients.
Interactions
Isoprenaline should not be given
concomitantly with other potent beta-1 agonists such as
adrenaline.
For the interactions of sympathomimetics in gener-
al. see Adrenaline
Theophylline. There are reports of increased theophylline
clearance following concomitant use of isoprenaline.
Pharmacokinetics
As a result of sulphate conjugation in the gut, isopre-
naline is considerably less active following adminis-
tration by mouth than following parenteral
administration. It is absorbed through the oral mu-
cosa and has accordingly been given sublingually.
but absorption by this route remains very erratic.
Isoprenaline in the body is resistant to metabolism
by monoamine oxidase, but is metabolised by cate-
chol-O-methyltransferase in the liver, lungs, and
other tissues, this metabolite being subsequently
conjugated before excretion in the urine. Whereas
the sulphate conjugate of isoprenaline is inactive the
methylated metabolite exhibits weak activity.
Following intravenous injection isoprenaline has a
plasma half-life of about one to several minutes ac-
cording to whether the rate of injection is rapid or
slow; it is almost entirely excreted in the urine as
unchanged drug and metabolites within 24 hours. A
much slower onset of action and a more extended
initial half-life has been demonstrated following
oral administration. Isoprenaline is reported to have
a duration of action of up to about 2 hours after in-
halation: it has been demonstrated that a large pro-
portion of an inhaled dose is swallowed.
Uses and Administration
Isoprenaline is a sympathomimetic that acts almost exclusively
on beta-adrenergic receptors. It stimulates the CNS. It has a
powerful stimulating action on the heart and increases
cardiac output, excitability, and rate: it also causes
peripheral vasodilatation and produces a fall in di-
astolic blood pressure and usually maintains or
slightly increases systolic blood pressure. In addi-
tion isoprenaline has bronchodilating properties.
Isoprenaline has been used in a variety of cardiac
disorders. It may be used for the temporary preven-
tion or control of Stokes--Adams attacks although for
long-term management the use of a pacemaker is
preferable. Isoprenaline may be useful in severe
bradycardia unresponsive to atropine, although
again cardiac pacing is preferred. It has also been
advocated as an adjunct for other cardiac disorders
including shock and torsade de pointes.
It has been used in the diagnosis of congen-
ital heart defects.
In the management of cardiac disorders, isoprena-
line is usually given as the hydrochloride by slow
intravenous infusion under ECG control. Infusion
rates may range from 0.5 to 10 mcg per minute de-
pending on the clinical condition of the patient; I to
4 ug per minute may be adequate to correct brady-
cardia but higher rates of 4 to 8 ng per minute may
be required for acute Stokes-Adams attacks. Isopre-
naline hydrochloride can be given by intracardiac
injection in extreme cases. It has also been given
subcutaneously or intramuscularly in initial doses of
200 mcg (as I mL of a 0.02% solution) and by slow
intravenous injection in initial doses of 20 to 60 mcg
(as I to 3 mL of a 0.002% solution); doses are sub-
sequently adjusted according to ventricular rate.
Tablets of isoprenaline hydrochloride have been ad-
ministered by mouth or sublingually.
Isoprenaline has been used as a bronchodilator in
the management of reversible airways obstruction
but sympathomimetics with a selective action on
beta, receptors, such as salbutamol, are now pre-
ferred . It is given as the sul-
phate or hydrochloride usually by inhalation;
sublingua] tablets and intravenous injections have
also been used. The adult dosage has generally been
I to 3 inhalations of isoprenaline sulphate 80 ng by
metered dose inhaler, repeated if necessary after not
less than 30 minutes up to a maximum of 8 treat-
ments in 24 hours. An aerosol inhaler which delivers
metered doses of 400 mcg has also been employed.
Solutions containing about 0.1% isoprenaline hy-
drochloride may be administered by nebulisation;
solutions up to 1% have been used in a hand-bulb
nebuliser. Isoprenaline hydrochloride has also been
given by sublingual administration in the manage-
ment of bronchospasm in usual doses of 10 to 15 mg
three or four times daily.
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