||Central α2-agonist (200:1 α2:α1)
||Analgesia, sedation, anti-hypertensive
||Antihypertensive (especially in pregnancy)
||Clear colourless solution at 150μg.ml-1
||Tablets - not appropriate for urgent blood pressure reduction
|Route of Administration
||PO/IV at 10-200mcg up to QID. Can be added to neuraxial blockade at 1-2mcg.kg-1 to decrease opioid requirement.
||250-500mg PO BD/TDS.
||100% PO bioavailability with rapid absorption
||Highly variable PO bioavailability
||20% bound, VD 2L.kg-1
||50% protein bound, VD 0.3L.kg-1
||50% hepatic to inactive metabolites, t1/2β 9-18 hours
||Intestinal and hepatic
||50% renal elimination unchanged
||40% renal elimination unchanged
|Mechanism of Action
||Agonist of central α2 receptor, ↓ SNS tone via decreased NA release from peripheral nerve terminals.
||Metabolised to α-methyl-noradrenaline in the CNS, which agonises central α2 receptors.
||Initial ↑ in BP due to α1 stimulation, evident with bolus dosing. Followed by prolonged ↓ in BP, ↑ PR, ↓ AV conduction, ↑ baroreceptor sensitisation (lower HR for a given increase in BP). Cessation may cause rebound HTN.
||↓ SVR with unchanged HR or CO
||Sedation, analgesia due to ↓ NA release which ↓ opioid requirement. Adjunct in chronic pain and in opioid withdrawal. Anxiolysis at low doses. Central antiemetic effect.
||May ↓ MAC
||Stress response to surgical stimulus is inhibited
||Diuresis secondary to inhibition of ADH