increases the sensitivity GABAA receptors which open (via GABA) and allow Cl influx
causing hyperpolarisation
- Influx of Cl- into nerve cell
- Hyperpolarised, preventing conduction

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)

CNS: Sedative, reduces epileptiform activity,
increases confusion and disorientation, amnesic properties more prominent than
sedative eff¬ects
CVS: minor hypotension has been reported

Resp: respiratory depression - synergistic with opioids

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

A : IV,PO,In,IM
poor oral bioavailability 45%

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

lipid soluble at physiological pH (pKa 6.5).
high lipid sol crosses BBB

Lipid soluble (rapid distribution)

Approximately 96% protein-bound in plasma.

95%

Volume of distribution approximately 0.8-1.5 L/kg, increasing to about 3.1 L/kg in critically ill patients.

2l/kg (steady state)

hepatic via CYP3A4, and glucuronidation
active metabolite

Hepatic via CYP and glucuronidation
inactive metabolites

excreted in urine (as glucuronide conjugated metabolites)

Inactive metabolites Excreted in urine

half life 1-4 hrs
prolonged in cirrhosis, CRF, CCF, obesity, elderly

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

Respiratory depression and excessive sedation with overdosage
Same CYP as alfentanil (increases e¬ffect)

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

- Imidazole ring in its structure - Accounts for water solubility And rapid metabolism
- 2-3x potent Diazepam

D-stereoisomer

Anticonvulsant Sedative-Hypnotic

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

Sedative, amnesic+ anxiolytic,
antiepileptic

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

- Benzodiazepine
- Imidazole ring in its structure - Accounts for water solubility And rapid metabolism
- 2-3x potent Diazepam

Central alpha2 agonist
Greater selectivity for A2 than clonidine

Level 1

Level 1

Clear solution pH 3.5 (IV/IM), Tablet
pKa 6.5 – 89% un-ionized

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

2-2.5mg initially then 1mg boluses to eff¬ect

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.