Pharmacology for Anaesthesia and Intensive Care

P1: PCX Printer: Yet To Come
9780521704632c10 CUFX213A/Peck 9780521618168 December 28, 2007 11:41

10 Local anaesthetics

the Na+channels, resulting in persistent depression. This may lead to re-entrant

arrhythmias and ventricular fibrillation. In addition, tachycardia may enhance

frequency-dependent blockade by bupivacaine, which adds to its cardiac toxicity.

Life-threatening arrhythmias may also reflect disruption of Ca^2 +and K+channels.

Ropivacaine differs from bupivacaine both in the substitution of a propyl for a butyl

group and in its preparation as a single, S, enantiomer. It dissociates more rapidly

from cardiac Na+channels and produces less direct myocardial depression than

bupivacaine, and is, therefore, less toxic. However, it has a slightly shorter duration

of action and is slightly less potent than bupivacaine resulting in a slightly larger

dose requirement for an equivalent block.


Central nervous system – local anaesthetics penetrate the brain rapidly and have a

bi-phasic effect. Initially inhibitory interneurones are blocked resulting in excita-

tory phenomenon – circumoral tingling, visual disturbance, tremors, and dizziness.

This is followed by convulsions. Finally, all central neurones are depressed leading

to coma and apnoea.

Kinetics

Absorption

The absorption of local anaesthetics into the systemic circulation varies depending

on the characteristics of the agent used, the presence of added vasoconstrictor and

the site of injection.

Lowest systemic concentrations

Highest systemic concentrations

intercostal

caudal

epidural

brachial plexus

subcutaneous

Clearly, if local anaesthetic is inadvertently injected into a vein or artery, very high

systemic levels will result and possibly cause central nervous system or cardiovas-

cular toxicity. Less than 10 mg lidocaine inadvertently injected into the carotid or

vertebral artery will result in a rapid rise in central nervous system concentrations

and will cause coma and possibly apnoea and cardiac arrest.

Distribution

Ester local anaesthetics are minimally bound while amides are more extensively

bound (bupivacaine > ropivacaine > lidocaine > prilocaine) in the plasma.α 1 -Acid

glycoprotein binds local anaesthetic with high affinity although albumin binds a

greater quantity due to its relative abundance. When protein binding is increased