Specific alpha-2 agonist acting primarily in the locus coeruleus to increase conductance through K+ channels. 8 times more selective than clonidine. Acts on all 3 subtypes of alpha-2R (A, B, C)

NMDA receptor antagonism
- Inhibits excitatory signaling within CNS
- Also inhibits noradrenaline reuptake in sympathetic nerve terminals

CNS
- Decreased sympathetic activity
- Decreased agitation
- Induces state resembling non-REM sleep without impairment of cognitive function. Easily roused but sedated.
- Analgesia produced in the posterior horns of the spinal cord, reduces need for opioid analgesia
- Decreases circulating cerebral catecholamines
- Decreases CBF/CMRO2/Mild decrease in ICP
- Decreases shivering

CVS: Decreased MAP and HR

Resp: Clinically insignificant increase in PaCO2 and decrease in RR

CNS: Causes dissociative anaesthesia
- Hallucinations
- Emergence delirium

CVS: Indirect sympathomimetic
chronotropy, inotrophy and Hypertension
Direct cardiodepressant
 if depletion of NA  hypotension
Resp - Bronchodilation

Intravenous administration bypasses an absorption phase. For procedural sedation, clinically effective sedation after a loading infusion is typically seen within about 10-15 minutes.

A: 20% oral bioavailability

Lipid soluble (rapid distribution)

95%

25%

2l/kg (steady state)

3l/kg

Hepatic via CYP and glucuronidation
inactive metabolites

Hepatic metabolism with active
norketamine metabolite

Inactive metabolites Excreted in urine

Renal elimination

Large variation in CSHT with infusion length (T1/2 5 minutes after 10 minutes IV, T1/2 240 minutes after 8 hour IV)

T1/2a 15 mins, T1/2b
2~3 hours, CSHT 40mins at 5 hours

- Transient hypertension (due to peripheral smooth muscle α2B agonism) -> reflex bradycardia Later, hypotension and bradycardia. Rebound HTN on ceasing dose - Dry mouth - nausea

Increased salivation - Upper airway reflexes intact  laryngospasm - Hypotension if given in shock states - Emergence delirium

D-stereoisomer

Highly selective alpha-2 adrenoceptor agonist sedative with sympatholytic properties.

Sedative/hypnotic with non-opioid analgesic properties.

Sedation of ventilated adult ICU patients and procedural sedation of non-intubated adults. Also used for awake fibreoptic intubation in selected patients.

Induction of anaesthesia
- Procedural sedation
- Analgesia
- ?Role in management of depression. - Recreational

Central alpha2 agonist
Greater selectivity for A2 than clonidine

Phencyclidine (remember the street drug name PCP) derivative that
produces dissociative anesthesia

Level 1

Level 1

Clear, colourless dexmedetomidine hydrochloride solution for intravenous use. Current Australian product information includes 200 micrograms in 2 mL vials.

10, 50 or 100mg/ml

ICU sedation: maintenance infusion generally 0.2-1 microgram/kg/hour, titrated to the required level. A loading dose may be omitted when converting from another sedative. Procedural sedation: loading dose 1 microgram/kg over 10-20 minutes followed by 0.2-1 microgram/kg/hour, titrated to effect.

- 1mg/kg induction dose
- 10~20mg analgesia