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

useful effects of clonidine rest on its ability to stimulate alpha2 receptors in
the lateral reticular nucleus resulting in decreased central sympathetic outflow by
a positive feedback mechanism, and in the spinal cord where it augments
endogenous opiate release and modulates descending noradrenergic pathways.

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

CVS
- transient increase in BP due to alpha2 agonism peripherally but this is followed by a more prolonged fall in BP.
- CO is usually maintained despite bradycardia.

CNS
- sedation and anxiolysis at low doses but anxigenic at higher doses.
- Provides analgesia without respiratory centre depression and is synergistic with opiods.

Renal
- inhibition of ADH may be the cause of diuresis. Endocrine
- stress response to surgery inhibited. Insulin release in reduced, usually BSL ok

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 Immediate release: 75% to 85%
routes of administration Oral, IV and IM

Lipid soluble (rapid distribution)

lipid solubility highly lipid soluble in order to cross the BBB

95%

20% to 40%

2l/kg (steady state)

2.1 L/kg

Hepatic via CYP and glucuronidation
inactive metabolites

Extensively hepatic to inactive metabolites

Inactive metabolites Excreted in urine

Inactive metabolites
Excreted in urine

Excreted in urine

Urine (40% to 60% as unchanged drug)

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

12-16 hours (increased in pts with renal disease)

- 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

- multiple effects of this drug make it intolerable to many patients, with
somnolence and dry mouth being a frequent concern.
- It may cause profound bradycardia if used with beta blockers.
- If withdrawn suddenly it may cause a rebound hypertension

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

- refractory hypertension
- adjunct in pain management and during anaesthesia
- in patients withdrawing from opiods
- diagnosis of phaechromocytoma

Central alpha2 agonist
Greater selectivity for A2 than clonidine

partial alpha agonist with an affinity for alpha2 receptors 200 times that for alpha1 receptors

-

Level 1

Level 3

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

both in oral form as a white tablet in dosages of 100-150mcg and
IV/IM forms as a colourless solution with 150mcg/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.

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

0.3-1mcg/kg/hr

PO/IV/IM
doses usually 150-300mcg twice daily