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

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