Monograph: |
Noradrenaline Hydrochloride
A white or brownish white, crystalline powder. It becomes
coloured on exposure io air and light. Noradrenaline hydro-
chloride 1.2 micrograms is approximately equivalent to I mi-
crogram of noradrenaline. Very soluble in water: slightly
soluble in alcohol. A 2% solution in water has a pH of 3.5 to
4.5. Store in airtight containers, or preferably, in a sealed
tube
under vacuum or an inert gas. Protect from light.
Adverse Effects
Noradrenaline is an extremely potent peripheral va-
soconstrictor and hypertension (possibly associated
with reflex bradycardia), headache, and peripheral
ischaemia which may be severe enough to result in
gangrene of the extremities, are among the potential
adverse effects.
Noradrenaline is a severe tissue irritant and only
very dilute solutions should be injected. The needle
must be inserted well into the vein to avoid extrava-
sation, otherwise severe phlebitis and sloughing
may occur.
For the adverse effects of sympathomimetics in gen-
eral, see Adrenaline.
Severe headache, once with fatal cerebral haemorrhage, had
been reported in dental patients who had received injections
of lignocaine 2% with noradrenaline I in 25 000. It was sug-
gested that a concentration of noradrenaline I in 25 000 was
too high and could not be justified and that a concentration of
I in 80 000 was to be preferred. However, authorities in the
UK now consider that noradrenaline should not be used as a
vasoconstrictor in local anaesthetic solutions since it presents
no advantages over adrenaline and carries additional hazard.
Treatment of Adverse Effects
The hypertensive effects of noradrenaline may be
treated with an alpha-adrenoceptor blocker such as
phentolamine. If extravasation occurs, infiltration
with phentolamine as soon as possible,
and certainly within 12 hours, may relieve pain and
prevent tissue necrosis.
Precautions
Noradrenaline must be avoided in the presence of
hypertension and blood pressure and infusion rate
must be monitored frequently. Noradrenaline-in-
duced cardiac arrhythmias are more likely in pa-
tients with hypoxia or hypercapnia. Hypovolaemia
should be corrected before starting noradrenaline in-
fusion.
Noradrenaline may reduce placental perfusion
throughout pregnancy and some consider that it and
similar vasoconstrictor sympathomimetics are best
avoided; also in late pregnancy noradrenaline pro-
vokes uterine contractions which can result in fetal
mortality.
For the precautions to be observed with sympatho-
mimetics in general, see Adrenaline.
Interactions
For the interactions of the sympathomimetics in
general, see Adrenaline.
Pharmacokinetics
Like adrenaline , noradrenaline is inactive
when given by mouth, and it is rapidly inactivated in
the body by similar processes. When given intrave-
nously it is extensively metabolised and only small
amounts are excreted unchanged in the urine of
healthy subjects.
Uses and Administration
The catecholamine. noradrenaline, is a direct-acting
sympathomimetic with pronounced effects on alpha-
adrenergic receptors and
less marked effects on beta-adrenergic receptors. It
is a neurotransmitter, stored in granules in nerve ax-
ons, which is released at the terminations of post
ganglionic adrenergic nerve fibres when they are
stimulated; some is also present in the adrenal me-
dulla from which it is liberated together with adren-
aline. A major effect of noradrenaline is to raise
systolic and diastolic blood pressure (which is ac-
companied by reflex slowing of the heart rate). This
is a result of its alpha-stimulant effects which cause
vasoconstriction. with reduced blood flow in the
kidneys, liver, skin, and usually skeletal muscle. The
pregnant uterus also contracts; high doses liberate
glucose from the liver and have other hormonal ef-
fects similar to those of adrenaline. There is little
stimulation of the central nervous system. Beta-
stimulant effects of noradrenaline have a positive in-
otropic action on the heart, but there is little bron-
chodilator effect.
Noradrenaline is used for the emergency restoration
of blood pressure in acute hypotensive states
It has been used in local anaesthesia to di-
minish the absorption and localize the effect of the
local anaesthetic but adrenaline is now pre-
ferred (see also under Adverse Effects, above). Lo-
cally applied solutions have been used to control
bleeding in upper gastro-intestinal haemorrhage and
similar disorders.
In acute hypotensive states, noradrenaline is ad-
ministered as the acid tartrate by intravenous infu-
sion of a solution containing the equivalent of 4 (ig
of the base per mL in glucose 5%, or sodium chlo-
ride 0.9% and glucose 5%. To avoid tissue necrosis
the infusion should be administered through a cen-
tral venous catheter or into a large vein high up in a
limb, preferably the arm. Some sources have sug-
gested that addition of phentolamine 5 to 10 mg per
litre to the infusion may prevent sloughing, should
extravasation occur, without affecting the vasopres-
sor action. The infusion is usually given initially at
a rate of 2 to 3 mL per minute (8 to 12 ng per
minute) and adjusted according to the blood pres-
sure response. Blood pressure is initially recorded
every 2 minutes and the rate of infusion continuous-
ly monitored. The infusion must not be stopped sud-
denly but should be gradually withdrawn to avoid
disastrous falls in blood pressure. The average main-
tenance dose is 0.5 to I mL per minute (2 to 4 p.g per
minute), but there is a wide variation and higher dos-
es may be required. The concentration of the infu-
sion may be altered according to clinical needs.
Alternatively a solution containing the equivalent of
40 ng of the base per mL may be given at an initial
rate of 0.16 to 0.33 mL per minute via a central ve-
nous catheter, using a syringe pump or drip counter.
Noradrenaline may also be given parenterally as the
hydrochloride in the management of hypotensive
states.
Similar doses may be given to restore blood pressure
following cardiac arrest. In patients with cardiac
standstill, a more concentrated solution of the acid
tartrate equivalent to 100 mcg of the base per mL can
be given by rapid intravenous or intracardiac injec-
tion: a dose of 0.5 to 0.75 mL (50 to 75 mcg of no-
radrenaline) has been suggested which may be
repeated if necessary.
|