

102
Chapter 8
Table 1.
Pharmacology of dexmedetomidine and clonidine
Dexmedetomidine
Clonidine
α
2
:α
1
1620:1
α
2
:α
1
220:1
α
2
A-receptor
Imidazole-receptor
T
1/2
= 2 h
T
1/2
= 8 h
Intravenous, intramuscular
Intravenous, intrathecal, oral
No rebound effect
Rebound effect
Pharmacokinetics
Dexmedetomidine has a distribution half-life of 6 minutes and an elimination half-life
of approximately 2 hours. Even with prolonged treatment, no accumulation is seen.
Dexmedetomidine is for 94% bound to plasma proteins and is almost completely
degraded by the liver. The various metabolites have negligible pharmacological activity
and are excreted by the kidneys for 95% and for 4% via faeces. Less than 1% is eliminated
unmetabolised in the urine. It should be considered to reduce the starting dose for
patients with hepatic impairment. Patients with renal impairment do not show altered
pharmacokinetics compared to healthy subjects. No significant pharmacokinetic differences
are observed based on age or gender.
Receptors
Α
2
-receptors are located pre-, extra-, and postsynaptic (Figure 1). They are found in the
peripheral and central nervous system, on platelets and various organs such as the liver,
pancreas, kidneys, and eyes. The presynaptic α
2
-receptors appear clinically more relevant.
They regulate the release of norepinephrine and ATP via a negative feedback mechanism.
Α
2
-receptors are G-protein coupled: stimulation of the receptor leads to activation of various
G-proteins. These proteins initiate an enzyme cascade that finally leads to the inhibition of
the calcium-entry into the nerve endings with a reduced release of norepinephrine. Aside,
G-proteins adapt via a second-messenger system ion channels, thereby inducing an efflux
of potassium ions. This allows for a hyperpolarisation of the cell membrane. In summary,
activation of α
2
-receptors diminishes the release of noradrenaline and inhibits neuronal
activity.
5
Mechanism of action
The desired effects of α
2
-agonists are sedation, anxiolysis, and analgesia. These effects are
mediated via different receptors. There are also (unwanted) central and peripheral side
effects. The receptors are divided into α
2
A-, α
2
B- and α
2
C-receptors triggering analgesic,
vasoconstrictive, and anxiolytic effects mainly due to the location of the different receptors
in the body.