A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

LOCAL ANAESTHETICS 153
have also proved useful in combination with general anaesthesia.
Local anaesthetics reversibly block impulse transmission
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 recommended
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 endarteries
(‘ring’ blocks of the digits and penis) because of the
risk of vasospasm and consequent ischaemia.
LIDOCAINE
Lidocaine is 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 addition
to injection, lidocaine can 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
Prilocaine is 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 concentration
is likely (e.g. injection into vascular areas, such as
the perineum), or for use in intravenous regional anaesthesia
(e.g. Biers’ block). EMLA is a ‘eutectic mixture of local anaesthetic’
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 anaesthesia
for venepuncture (important, especially for children). In
dental procedures, prilocaine is often used with the peptide
vasoconstrictor felypressin. Excessive doses can lead to systemic
toxicity, dependent on plasma concentration.
Prilocaine is metabolized by amidases in the liver, kidney
and lungs. The rapid production of oxidation products may
rarely give rise to methaemoglobinaemia.
BUPIVACAINE
Bupivacaine is a long-acting amide local anaesthetic commonly
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 lidocaine.
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 bupivacaine is similar
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 defibrillation.
For this reason, it should not be used in intravenous
regional anaesthesia.
ROPIVACAINE
Ropivacaine is 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 inadvertently
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 collapse,
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.