INTRAVENOUS ANAESTHETICS - 4

Drug

Agent

Thiopentone

Methohexitone

Propofol

Ketamine

Class

Thiobarbiturate

Oxybarbiturate

Phenol

Phencyclidine

Structure

Formulation

0.5g STP anhydrous

30mg Na₂CO₃

0.8atm N₂

20ml 2.5% soln

pH 11 (enol)

stable 1 wk

0.5g anhydrous

30mg Na₂CO₃

50ml 1% soln

pH 11 (enol)

stable 6 wks

10% soyabean oil

2.25% glycerol

1.2% egg phosph

1% propofol

NaOH→pH 6-8.5

Store 2 - 25C

Ket HCl 200mg/2ml

pH 3.5-5.5

Benzthomium

Racemic mix

Partial H2O sol

Isomers

Levo potency = 2x dextro

4 stereoisomers

β-l potency = 4 x α-l

but β excess motor, so racemic mix α isomers

S isomer more potent analgesic, faster metabolism, less emergence phenomena

P/kin

pKa

7.6 (acid)

7.9 (acid)

11 (acid)

7.5 (acid)

% unionised @ pH 7.4

60

75

90

60

Lipid solubility

Thio>>Metho

Fat:blood 11

Thio>>Metho

Highly

5-10 x thio

PPB (%)

80% (albumin)

60% (albumin)

98%

12%

V_dss (L/kg)

2.5

2.2

2-10

3-8

CL(ml/kg/min)

3.4

11.9

30 (>Q_H)?kidney,SI

19

Hepatic

metabolism

LHER (high PPB)

pentobarbitone

HHER

No active metab

Inactive conjugates

HHER

Norketamine

Renal excretion

<1%>

<1%>

<1%>

t½α (min)

8.5

5.6

1-2

11

t½β (hr)

11.6

3.9

4-23

1.5

Admin

Dose

3-5mg/kg adult

7-8mg/kg kid

↑ dose for chronic EtOH

1-1.5mg/kg

1-2.5mg/kg adult

2-3mg/kg kid

100-300mcg/kg/min

25-100mcg/kg/m (sedate)

1-2mg/kg

2-10mcg/kg/min analgesia

Hepatic failure

↓ (hypoproteinaemia)

Vc, Vd, CL same, t1/2 sl

Renal failure

↓(hypoproteinaemia)

Minimal effect

Target level

3-4mcg/ml

Onset

One arm-brain

30secs

One arm-brain

30secs

30secs

Peak biophase conc after iv

1min

1.5mins

1min

Duration

5-10min

2-3min

(use ECT)

5-10mins

5-10min anaesthesia

1-2hrs analgesia

Offset

Redistribution

VRG 1min

Muscle 15min

Fat 2.5hr

Redistribution

Redistribution & metabolism

Redistribution