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Section IIICardiovascular drugsKinetics
Forendogenously released noradrenaline, Uptake 1 describes its active uptake back
into the nerve terminal where it is metabolized by MAO (COMT is not present in sym-
pathetic nerves) or recycled. It forms the main mechanism by which noradrenaline is
inactivated. Uptake 2 describes the diffusion away from the nerve and is less impor-
tant. Noradrenaline reaches the circulation in this way and is metabolized by COMT
to the inactive 3-methoxy–4-hydroxymandelic acid (vanillylmandelic acid or VMA)
and normetadrenaline, which is conjugated with glucuronic acid or sulphates, both
of which are excreted in the urine. It has a short half-life (about 2 minutes) due
to rapid metabolism. Unlike adrenaline and dopamine, up to 25% is taken up as it
passes through the lungs.Dopamine
Incertain cells within the brain and interneurones of the autonomic ganglia, do-
pamine is not converted to noradrenaline and is released as a neurotransmitter.Presentation and uses
Dopamine is presented as a clear solution containing 200 or 800 mg in 5 ml water
with sodium metabisulphite. It is used to improve haemodynamic parameters and
urine output.Mechanism of action
Inaddition to its effects onαandβadrenoceptors, dopamine also acts via dopamine
(D 1 and D 2 )receptors via Gsand Gicoupled adenylate cyclase leading to increased
or decreased levels of cAMP.Effects
Cardiovascular – these depend on its rate of infusion and vary between patients.
Atlower rates (up to 10μg.kg−^1 .min−^1 )β 1 effects predominate leading to
increased contractility, heart rate, cardiac output and coronary blood flow. In
addition to its direct effects, it also stimulates the release of endogenous nora-
drenaline. At higher rates (>10μg.kg−^1 .min−^1 )αeffects tend to predominate
leading to increased systemic vascular resistance and venous return. In keep-
ing with other inotropes an adequate preload is essential to help control tachy-
cardia. It is less arrhythmogenic than adrenaline. Extravasation can cause tissue
necrosis.
Respiratory – infusions of dopamine attenuate the response of the carotid body to
hypoxaemia. Pulmonary vascular resistance is increased.
Splanchnic – dopamine has been shown to vasodilate mesenteric vessels via D 1
receptors. However, the improvement in urine output may be entirely due to