Pharmacology for Anaesthesia and Intensive Care

P1: PCX Printer: Yet To Come
9780521704632c08 CUFX213A/Peck 9780521618168 December 28, 2007 10:38

8 General anaesthetic agents

Table 8.6.Metabolism of inhaled anaesthetic agents.

Agent Percentage metabolized Metabolites

N 2 O <0.01 (N 2 )

Halothane 20 Trifluoroacetic acid, Cl−,Br−

Sevoflurane 3.5 Inorganic and organic fluorides

Compound A in the presence of soda lime and heat

(Compound B, C, D and E)

Enflurane 2 Inorganic and organic fluorides

Isoflurane 0.2 Trifluroacetic acid and F−

Desflurane 0.02 Trifluroacetic acid

Although it might be expected that agents with a high blood:gas partition coef-

ficient (i.e. high solubility) would have a rapid onset, this is not the case because

these agents only exert a low partial pressure in blood, even when present in large

amounts. It is the partial pressure of the agent in the blood and subsequently the

brain that gives rise to anaesthesia and not the total amount present. Agents with a

low blood:gas partition coefficient exert a high partial pressure and will, therefore,

produce a more rapid onset and offset of action. Although a low blood:gas partition

coefficient is important, MAC and respiratory irritability can also alter the speed of

induction.

Concentration and second gas effect

These are described in the section on nitrous oxide.

Metabolism

Hepatic cytochrome P450 metabolizes the C-(halogen) bond to release halogen ions

(F−,Cl−Br−), which may cause hepatic or renal damage. The C–F bond is a stable

one and is only minimally metabolized unlike C–Cl, C–Br and C–I which become

progressively easy to metabolize (Table8.6).

Pharmacology of inhaled anaesthetic agents

Nitrous oxide

Nitrous oxide (N 2 O) is used widely alongside the volatile agents and in combination

with oxygen (O 2 )asentonox. Apart from a high MAC, it has favourable physical

properties. However, during even relatively short exposure it interferes with DNA

synthesis and increasing concern over this and other aspects of N 2 Omay limit its

future use.

Manufacture

Nitrous oxide is manufactured by heating ammonium nitrate to 250◦C.

NH 4 NO 3 →N 2 O+2H 2 O