| Class |
Central α2-agonist (200:1 α2:α1) |
Phenylalanine derivative |
| Uses |
Analgesia, sedation, anti-hypertensive |
Antihypertensive (especially in pregnancy) |
| Presentation |
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. |
PO/IV. |
| Dosing |
50-200μg QID. |
250-500mg PO BD/TDS. |
| Absorption |
100% PO bioavailability with rapid absorption |
Highly variable PO bioavailability |
| Distribution |
20% bound, VD 2L.kg-1 |
50% protein bound, VD 0.3L.kg-1 |
| Metabolism |
50% hepatic to inactive metabolites, t1/2β 9-18 hours |
Intestinal and hepatic |
| Elimination |
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. |
| CVS |
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 |
| CNS |
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 |
| Metabolic |
Stress response to surgical stimulus is inhibited |
|
| Renal |
Diuresis secondary to inhibition of ADH |