Core pharmacology

Class Group

Sedative / Hypnotic

Introduction

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

Indications Uses

Short term sedation
Induction and maintenance of anaesthesia
Maintenance of sedation

Presentation

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

Mechanism of action

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

Physiological effects

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

Adverse Effects Toxicity

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

Absorption

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

Distribution

pKa 11
very high lipid sol
Crosses placenta

Protein binding

97-99%

Volume of distribution

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

Metabolism

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

Excretion

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

Half-life

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

Route And Dose

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