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)

Selective central α2 agonism
Inhibition of noradrenaline release in locus ceruleus
Peripherally at higher doses

Its metabolite produces a clonidine like alpha2 agonist effect in cardiovascular
control centres that results in reduced sympathetic outflow. The metabolite also
acts as a false neurotransmitter reducing peripheral SNS effects by reducing
noradrenaline synthesis.

Produces arousable sedation with minimal respiratory depression. Cardiovascular effects include bradycardia and hypotension, with transient hypertension possible during loading or higher exposure.

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: sedation: REM sleep-like state,min respiratory depression
Analgesia without as much confusion or disorientation as benzos. Pts easily aroused.
Spinal cord analgesia Decreases cerebral VO2, blood flow and ICP No antiemesis
CVS: Higher doses cause peripheral α2 effects – vasoconstriction,
followed by hypotension and bradycardia (Decreased sympathetic output)
Resp: Minimal Resp depression

It is primarily used to depress overall SNS activity (HR, BP and TPR) but can also cause sedation, psychosis and depression

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

Without loading dose (commonly not used because of bradycardia), 30 minutes to reach effective concentration

A: Without loading dose (commonly not used because of bradycardia), 30 minutes to reach effective concentration

bioavailabilty absorded by an amino acid transporter (% ?)
routes of administration oral
onset of action 3-6 hours, duration 24 hours (this is becuase
of the prolonged process in substituting for noradrenaline in
peripheral sites)

Lipid soluble (rapid distribution)

95%

<15%

2l/kg (steady state)

Hepatic via CYP and glucuronidation
inactive metabolites

mechanism Intestinal and hepatic

Inactive metabolites Excreted in urine

Inactive metabolites
Excreted in urine

Excreted in urine

Urine (85% as metabolites) within 24 hours

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

75-80 minutes (extended in renal failure)

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

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

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

- Sedation, decreased mental acuity and depression may occur.
- Dry mouth is also a
problem.
- A small percentage of patients develop hepatotoxicity or a haemolytic anaemia.

D-stereoisomer

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

Central Antihypertensive

Sedative / Hypnotic

Central Antihypertensive

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

1. Sedation
2. Analgesia
3. Delirium prevention and management
4. Withdrawal syndromes
5. Perioperative sympatholytic

Short term sedation
Adjunct sedative when ventilator weaning in delirious and agitated patients

significant adverse effects currently limit its use
- used in treatment of hypertension in pregnancy, where it has a record for safety

Central alpha2 agonist
Greater selectivity for A2 than clonidine

Central alpha2 agonist
exerts its antihypertensive action via an active metabolite.

-

Level 1

-

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

Clear, colourless solution
IV only in Aus (PO overseas)
Comparitively expensive

Clear, colourless solution
IV only in Aus (PO overseas)
Comparitively expensive, D-stereoisomer

oral formulation in Australia in 250mg tablets

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.

IV Infusion
Dose: 0.3-1mcg/kg/min

0.3-1mcg/kg/hr

PO
doses 125-250mg BD titrated