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9780521704632c16 CUFX213A/Peck 9780521618168 December 28, 2007 13:34
16 Antihypertensivesare complicated as any direct vasoconstriction may be offset by a reduction in
sympathetic tone and by the release of local nitric oxide. It stabilizes the cardio-
vascular responses to peri-operative stimuli. Rebound hypertension is seen more
commonly when a dose of more than 1.2 g.day−^1 is stopped abruptly. This is due
to peripheral vasoconstriction and increased plasma catecholamines and may
be exacerbated byβ-blockade (leaving vasoconstriction unopposed). Increasing
doses have a ceiling effect and are limited by increasingα 1 stimulation.
Central nervous system – it produces sedation and a reduction of up to 50% in
the MAC of volatile agents. It is anxiolytic at low doses but becomes anxiogenic at
higher doses.
Analgesia – clonidine has been used via the subarachnoid and epidural routes.
Itprovides prolonged analgesia with no respiratory depression and appears to
act synergistically with concurrently administered opioids. It does not produce
motor or sensory blockade. Clonidine also appears to reduce post-operative opioid
requirement when administered intravenously.
Renal system – a number of mechanisms including inhibition of release of ADH
have been implicated as the cause of diuresis during its use.
Respiratory – in contrast to opioids it does not produce significant respiratory
depression.
Endocrine – the stress response to surgical stimulus is inhibited. Insulin release is
inhibited although this rarely increases blood-sugar levels.
Haematological – despite the presence ofα 2 -adrenoceptors on platelets, therapeu-
tic doses of clonidine do not promote platelet aggregation and its sympatholytic
effects block adrenaline-induced platelet aggregation.Kinetics
Clonidine is rapidly and almost completely absorbed after oral administration,
achieving an oral bioavailability of nearly 100%. It is 20% plasma protein bound and
has a volume of distribution of about 2 l.kg−^1 .The elimination half-life of clonidine
is between 9 and 18 hours, with approximately 50% of the drug being metabolized
in the liver to inactive metabolites, while the rest is excreted unchanged in the urine.
The dose should be reduced in the presence of renal impairment.Dexmedetomidine
Medetomidine is anα 2 -agonist that has been used widely in veterinary practice for
its sedation and analgesic properties.Presentation and uses
Medetomidine is a racemic mixture but only thed-stereoisomer is active, so it has
been developed as dexmedetomidine.