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9780521704632c16 CUFX213A/Peck 9780521618168 December 28, 2007 13:34
Section IIICardiovascular drugsMechanism of action
This is similar to that of clonidine although it is more potent and has a higher affinity
for theα 2 -receptor (α 2 :α 1 ratio 1600:1). It is a full agonist.Effects
These are broadly similar to those of clonidine.Kinetics
Oral absorption is unpredictable but does avoid the initial hypertension that par-
enteral administration produces. It has an elimination half-life of 2 hours.Atipamezole
Atipamezole is a selectiveα 2 -antagonist that crosses the BBB to reverse the seda-
tion and analgesia associated with clonidine and dexmedetomidine. At 2 hours its
elimination half-life is similar to dexmedetomidine with obvious clinical benefit.Ganglion blockade
This group of drugs competitively antagonizes nicotinic receptors at both parasym-
pathetic and sympathetic ganglia and also at the adrenal cortex. Ganglion blockers do
not inhibit nicotinic receptors at the neuromuscular junction although some muscle
relaxants (tubocurare) may demonstrate some ganglion-blocking properties.Trimetaphan
Trimetaphan is a quaternary ammonium compound.Presentation and uses
Trimetaphan is available as a clear pale-yellow solution for intravenous injection
containing 50 mg.ml−^1 .Itwas used previously via the oral route to treat essential
hypertension but drugs with better side-effect profiles have superseded it. Its sole
current use is to induce hypotensive anaesthesia at 1–4 mg.min−^1.Mechanism of action
Trimetaphan is a competitive antagonist at all nicotinic ganglionic receptors includ-
ing those at the adrenal cortex and has a direct vasodilator effect on peripheral vessels.
Histamine is also released but may not be significant in producing hypotension.Effects
Cardiovascular – the onset of hypotension is rapid when used by intravenous infu-
sion. Pre- and afterload falls, and there may be a compensatory increase in heart
rate to maintain cardiac output.