Pharmacology for Anaesthesia and Intensive Care

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8 General anaesthetic agents

compounds have also been used, however poor solubility (pregnalolone) together

with an association with anaphylactic reactions (due to cremophor EL – used to

solubalize the steroid althesin) has led to their demise.

The ideal intravenous anaesthetic agent

Werean ideal intravenous anaesthetic agent to exist, it should have the following

properties:


Rapid onset (mainly unionized at physiological pH)


High lipid solubility


Rapid recovery, no accumulation during prolonged infusion


Analgesic at sub-anaesthetic concentrations


Minimal cardiovascular and respiratory depression


Noemetic effects


Nopain on injection


Noexcitation or emergence phenomena


Nointeraction with other agents


Safe following inadvertent intra-arterial injection


Notoxic effects


Nohistamine release


Nohypersensitivity reactions


Water-soluble formulation


Long shelf-life at room temperature

The currently used agents are discussed below under the following headings:


Barbiturates (thiopental, methohexitone)


Non-barbiturates (propofol, ketamine, etomidate)

Barbiturates

All barbiturates are derived from barbituric acid, which is the condensation product

of urea and malonic acid (Figure8.3). When oxygen is exchanged for sulphur at the

C2 position, oxybarbiturates become thiobarbiturates.

Barbiturates are not readily soluble in water at neutral pH. Their solubility depends

on transformation from the keto to the enol form (tautomerism), which occurs most

Urea

NH 2

NH 2

N

N

H

H

O C CH 2 2 CH 2 2H 2 O

HO

HO

O

C

O C

C

OO

O

C

C

Malonic acid Barbituric acid + water

—— ——

—— ——

—— ——

—— ——

—

—

—

—

—

—

—

—

—

6 —

5

3 4

1

+

Figure 8.3.Formation of barbituric acid.