A Textbook of Clinical Pharmacology and Therapeutics

have also proved useful in combination with general anaes-
thesia. Local anaesthetics reversibly block impulse transmis-
sion in peripheral nerves. They consist of an aromatic group
joined by an intermediate chain to an amine and are injected
in their ionized water-soluble form. In tissues a proportion of
the drug dissociates to lipid-soluble free base. The free base is
able to cross neuronal lipid membrane. Ionized drug enters
and blocks sodium channels blocking nerve action potentials.
Local anaesthetics depress small unmyelinated fibres first and
larger myelinated fibres last. The order of loss of function is
therefore as follows:

• pain;


• temperature;


• touch;


• motor function.

SYSTEMIC TOXICITY

Inadvertent intravascular injection is the most common cause
of systemic toxicity: gentle suction to check that blood does
not enter the syringe is vital before injection. Even when injected
by the correct route, toxicity may result from overdose, so rec-
ommended safe doses should not be exceeded. Early signs of
toxicity are circumoral numbness and tingling, which may be
followed by drowsiness, anxiety and tinnitus. In severe cases
there is loss of consciousness, and there may be convulsions
with subsequent coma, apnoea and cardiovascular collapse.
The addition of a vasoconstrictor such as adrenaline to a local
anaesthetic solution slows the rate of absorption, prolongs
duration and reduces toxicity. The concentration of adrenaline
should not be greater than 1:200 000. Preparations containing
adrenaline are contraindicated for injection close to end-
arteries (‘ring’ blocks of the digits and penis) because of the
risk of vasospasm and consequent ischaemia.

LIDOCAINE

Lidocaineis the most widely used local anaesthetic in the UK
(its use as an anti-dysrhythmic drug is discussed in Chapter 32).
It has a quick onset and medium duration of action. In addi-
tion to injection, lidocainecan be administered topically as
a gel or aerosol. It is used in all forms of local anaesthesia.
Absorption following topical application can be rapid (e.g.
from the larynx, bronchi or urethra). Systemic allergy is
uncommon.

PRILOCAINE

Prilocaineis similar to lidocaine, but its clearance is more
rapid, so it is less toxic. It is most useful when a large total
amount of local anaesthetic is needed or a high plasma con-
centration is likely (e.g. injection into vascular areas, such as
the perineum), or for use in intravenous regional anaesthesia

LOCALANAESTHETICS 153

(e.g. Biers’ block). EMLAis a ‘eutectic mixture of local anaes-

thetic’ and is a combination of prilocaine and lidocaine in the

form of a cream. If applied topically for 30–60 minutes and

covered with an occlusive dressing, it provides reliable anaes-

thesia for venepuncture (important, especially for children). In

dental procedures, prilocaineis often used with the peptide

vasoconstrictorfelypressin. Excessive doses can lead to sys-

temic toxicity, dependent on plasma concentration.

Prilocaineis metabolized by amidases in the liver, kidney

and lungs. The rapid production of oxidation products may

rarely give rise to methaemoglobinaemia.

BUPIVACAINE

Bupivacaineis a long-acting amide local anaesthetic com-

monly used for epidural and spinal anaesthesia. Although it

has a slow onset, peripheral nerve and plexus blockade can

have a duration of 5–12 hours. Epidural blockade is much

shorter, at about two hours, but is still longer than for lido-

caine. The relatively short duration of epidural block is related

to the high vascularity of the epidural space and consequent

rapid uptake of anaesthetic into the bloodstream. Bupivacaine

is the agent of choice for continuous epidural blockade in

obstetrics, as the rise in maternal (and therefore fetal) plasma

concentration occurs less rapidly than with lidocaine. The

acute central nervous system toxicity of bupivacaineis simi-

lar to that of lidocaine, it is thought to be more toxic to the

myocardium. The first sign of toxicity can be cardiac arrest

from ventricular fibrillation, which is often resistant to defib-

rillation. For this reason, it should not be used in intravenous

regional anaesthesia.

ROPIVACAINE

Ropivacaineis a propyl analogue of bupivacaine, and is the

only local anaesthetic that occurs in a single enantiomeric

form. It is marginally less potent than bupivacaine, with a

slightly shorter duration of action. Its advantages are that it

produces less motor block and less cardiac toxicity if inadvert-

ently administered intravenously.

COCAINE

The use of cocaine(see also Chapter 53) as a local anaesthetic

is restricted to topical application in ear, nose and throat (ENT)

procedures because of its adverse effects and potential for

abuse. Acute intoxication can occur, consisting of restlessness,

anxiety, confusion, tachycardia, angina, cardiovascular col-

lapse, convulsions, coma and death. In the central nervous

system, initial stimulation gives rise to excitement and raised

blood pressure followed by vomiting. This may be followed

by fits and CNS depression. It causes vasoconstriction, so

adrenaline must not be added.