selective modulation of GABA-A receptor (agonism)
(distinct from modulatory site for barbiturates and benzos, and GABA itself)
- Influx of Cl- into nerve cell
- Hyperpolarised, preventing conduction

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

CNS: Sedation and hypnosis
(Rapid distribution across BBB)
No analgesia
Burst suppression
Decreases cerebral VO2, blood flow and ICP
CVS: signifi¬cant drop in BP due to decreased TPR, but without a reflex tachycardia (infusion
rate dependent)
Resp: Dose dependent resp depression, apnoea
GIT: Anti-emetic

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

A: onset / duration 30 seconds / 3-10 minutes

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

pKa 11
very high lipid sol
Crosses placenta

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

97-99%

Approximately 96% protein-bound in plasma.

highly protein bound (95%)

95%

2-10L/kg
60l/kg after 10 day infusion
↓ in elderly

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

small-mod Vd = 1-2 L/kg
high lipid sol crosses BBB

1-2 L/kg

Hepatic to partially inactive metabolites (water soluble sulfate and glucuronide conjugates(~50%)
Clearance > liver blood flow, ∴extrahepatic metabolism

hepatic via CYP3A4, and glucuronidation
active metabolite

Urine (~88% as metabolites,40% as glucuronide)

excreted in urine (as glucuronide conjugated metabolites)

half life Biphasic: Initial 40 min; Terminal 4-7 hrs (up to 60hrs)

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

Hypotension (baroreceptor sens.
blunted, decreased sympathetic tone). Painful on injection.
Propofol syndrome: Metabolic acidosis, hyperlipidaemia, myocardial failure, death- common in children

Respiratory depression and excessive sedation with overdosage
Same CYP as alfentanil (increases effect)

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

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

Sedative / Hypnotic

Anticonvulsant Sedative-Hypnotic

Anticonvulsant
Sedative-Hypnotic

Sedative / Hypnotic

Short term sedation
Induction and maintenance of anaesthesia
Maintenance of sedation

Sedative, amnesic+ anxiolytic,
antiepileptic

2,6-di-isopropyl phenol Chemically inert phenolic derivative

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

Level 1

Level 1

Milky white emulsion 1%
Soya bean lipid/Egg phosphatide
Sodium hydroxide
Weak org acid pKa 11- unionised

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

Induction: 2-2.5mg/kg
Maintenance: 1-5mg/kg/hour
Both sig. less in critically ill

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