Describe the factors that increase the risk of systemic toxicity of the amide local anaesthetics. 

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College Answer

The amide group oflocal anaesthetics consist of lignocaine, prilocaine, ropivacaine and 
bupivacaine. The systemic toxicity primarily relates to toxic plasma levels and the factors 
that influence this. The main factors expected can be categorized under drug factors 
(including kinetics), patient factors, site of injection and external factors. Many candidates 
omitted important details such as pKA, lipid solubility and addition of vasoconstrictors. For 
example, absorption is affected by drug pKA, (thecloser to physiological pH themore rapid 
the absorption), use of vasoconstrictors and the drugs own vasoactive properties, site of 
injection (intercostal>epidural>brachial plexus>subcutaneous infiltration). Distribution is 
dependent on physicochemical properties of the amide. The rate of metabolism, mechanism 
of action (bupivacaine, in comparison to lignocaine has stronger binding to inactivated 
resting sodium channels and a slower rate of dissociation) and external factors (e.g.
systemic acidosis) are other factors that should have been mentioned, and expanded upon 
with relevant detail.