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15 VasodilatorsEffects
Cardiovascular – arterial vasodilation reduces the systemic vascular resistance and
leads to a drop in blood pressure. Venous vasodilation increases the venous capac-
itance and reduces preload. Cardiac output is maintained by a reflex tachycardia.
However, for those patients with heart failure the reduction in pre- and afterload
will increase cardiac output with no increase in heart rate. The ventricular wall ten-
sion and myocardial oxygen consumption are reduced. It has no direct effects on
contractility. Some patients develop tachyphylaxis, the exact mechanism of which
is unclear.
Respiratory – SNP may inhibit pulmonary hypoxic vasoconstriction and lead to
increased shunt. Supplemental oxygen may help.
Central nervous system – intracranial pressure is increased due to cerebral vasodi-
lation and increased cerebral blood flow. However, cerebral autoregulation is main-
tained well below the normal limits during SNP infusion. In addition, cerebral
function monitoring shows depressed cerebral function at a higher blood pressure
when hypotension is induced by trimetaphan compared with SNP.
Endocrine – plasma catecholamine and renin levels rise during SNP infusion.
Gut–paralytic ileus has been reported following hypotensive anaesthesia induced
bySNP. It is not clear if this is a direct effect or due to reduced mesenteric blood
flow or simply due to opioids.
General – the following effects are reversed when the rate of infusion is slowed: nau-
sea and vomiting, dizziness, abdominal pain, muscle twitching and retrosternal
pain.Kinetics
SNP is not absorbed following oral administration. It has a short half-life and its
duration of action is less than 10 minutes. However, the half-life of SCN is 2 days.Metabolism
The metabolism of SNP is complicated (Figure15.1). Initially within the red blood
cell it reacts with oxyhaemoglobin to form NO, five CN−ions and methaemoglobin.
The methaemoglobin may then combine with CN−to form cyanomethaemoglobin,
which is thought to be non-toxic.
The remaining CN−is then able to escape from the red blood cell where it is
converted in the liver and kidney by the mitochondrial enzyme rhodanase with the
addition of a sulphydryl group to form thiocyanate (SCN). Red blood cells contain
the enzyme thiocyanate oxidase, which can convert SCN back to CN−, but most
SCN is excreted in the urine. SCN has an elimination half-life of 2 days but this may
increase to 7 days in the presence of renal impairment. Alternatively CN−combines
with hydroxycobalamin (vitamin B 12 )toform cyanocobalamin, which forms a non-
toxic store of CN−and can be excreted in the urine.