A Textbook of Clinical Pharmacology and Therapeutics

●General anaesthetics 145

●Inhalational anaesthetics 145

●Intravenous anaesthetics 148

●Supplementary drugs 149

●Sedation in the intensive care unit 150

●Premedication for anaesthesia 150

●Muscle relaxants 150

●Malignant hyperthermia 152

●Local anaesthetics 152

CHAPTER 24

ANAESTHETICS AND MUSCLE

RELAXANTS

GENERAL ANAESTHETICS

The modern practice of anaesthesia most commonly involves
the administration of an intravenous anaesthetic agent to
induce rapid loss of consciousness, amnesia and inhibition of
autonomic and sensory reflexes. Anaesthesia is maintained
conventionally by the continuous administration of an inhala-
tional anaesthetic agent and cessation of administration results
in rapid recovery. An opioid is often administered for anal-
gesia, and in many cases a muscle relaxant is given in order to
produce paralysis. A combination of drugs is normally used
and the concept of a ‘triad of anaesthesia’ (Figure 24.1) describes
general anaesthesia as a combination of relaxation, hypnosis
and analgesia.

INHALATIONAL ANAESTHETICS

UPTAKE AND DISTRIBUTION

A few inhalational general anaesthetics are gases (e.g. nitrous
oxide), but most are volatile liquids (e.g. sevoflurane) which
are administered as vapours from calibrated vaporizers. None
of the drugs in current use is flammable (unlike ether!). The
anaesthetic vapours are carried to the patient in a mixture of

nitrous oxide and oxygen or oxygen-enriched air. The concen-

tration of an individual gas in a mixture of gases is propor-

tional to its partial pressure. It is the partial pressure of an

anaesthetic agent in the brain that determines the onset of anaes-

thesia, and this equates with the alveolar partial pressure of

that agent. The rate of induction and recovery from anaesthe-

sia depends on factors that determine the rate of transfer of

the anaesthetic agent from alveoli to arterial blood and from

arterial blood to brain (Figure 24.2):

• Anaesthetic concentration in the inspired air– increases in the
  inspired anaesthetic concentration increase the rate of
  induction of anaesthesia by increasing the rate of transfer
  into the blood.


• Relative solubility in blood– the blood:gas solubility
  coefficient defines the relative affinity of an anaesthetic for
  blood compared to air. Anaesthetic agents that are not very
  soluble in blood have a low blood:gas solubility coefficient,
  and the alveolar concentration during inhalationwill rise
  rapidly, as little drug is taken up into the circulation. Agents
  with low blood solubility rapidly produce high arterial
  tensions and therefore large concentration gradients
  between the blood and brain. This leads to rapid induction
  and, on discontinuing administration, rapid recovery.
  Agents with higher solubility in blood are associated with
  slower induction and slower recovery.

Hypnosis

Relaxation Analgesia

Figure 24.1:Triad of anaesthesia.

Anaesthetic

concentration

in inspired air

Rate of

anaesthesia

Anaesthetic

solubility in blood

Pulmonary

blood flow

Pulmonary

ventilation









(soluble agents)

Figure 24.2:Factors determining the onset of action of

inhalational anaesthetics.