INTRAVENOUS ANAESTHETICS - 2

Drug

Agent

Etomidate

Diazepam

Midazolam

Flumazenil

Class

Carboxylated Imidazole

Benzodiazepine

Imidazobenzodiazepine

Imidazobenzodiazepine

Structure

Formulation

2mg/ml

intralipid

pH 6.9

water sol in acidic

5mg/ml diazepam

40% propylene glycol

5% sodium benzoate

10% ethyl alcohol

1.5% benzyl alcohol

to pH 6.2-6.9

1 or 5mg/ml midaz HCl

0.8% NaCl

0.01% disodium edetate

1% benzyl alcohol (preservative)

HCl to pH 3

pH <>

Colourless crystalline powder

0.5mg/5ml

Isomers

P/kin

pKa

3.3

6.2

1.7

% unionised @ pH 7.4

Lipid solubility

high

Higher (pH > 4)

Moderate (weak but sufficient H2O sol)

PPB (%)

75% (alb)

98%

98%

60%

V_dss (L/kg)

2-4

1

1

1

CL(ml/kg/min)

20

0.2-0.5

6-8

20

Hepatic

metabolism

HHER

Oxidn and conjugation

Oxazepam, nordazepam active

Imidazole ring oxidised rapidly

Rapid

Renal excretion

t½α (min)

2.6

t½β (hr)

3-5

20-40

2-4

1

Admin

Dose

0.2-0.6 mg/kg

0.3-0.5mg/kg

0.1-0.2mg/kg

0.1-0.2mg to max 1mg

benzo OD

0.2-0.5mg to max 3mg

Dx coma

Hepatic failure

Renal failure

Target level

Onset

30-60sec

30-60sec

2mins

Peak biophase conc after iv

1-2mins

2-3mins

Duration

24-48hrs

<6hrs

1-2hrs (high free%, imidazole ring)

Offset

Redistribution and metabolism

Enterohepatic circ

redistrubution and metabolism