Esters
The toxicity of ester local anesthetics is closely related to the rate of their hydrolysis in the plasma. Because chloroprocaine is hydrolyzed rapidly, it has a low potential for systemic toxicity. On the other hand, tetracaine, which is hydrolyzed 16 times more slowly than chloroprocaine, has a significantly higher risk of causing toxic reactions. The production of PABA during ester metabolism is also responsible for the allergic reactions that some patients experience, although true allergic reactions to ester local anesthetics are rare.
In individuals with atypical pseudocholinesterase, the inability to metabolize ester local anesthetics leads to prolonged effects and an increased risk of toxicity. This condition represents a relative contraindication to the use of ester anesthetics. In these cases, the smallest effective dose should be administered, or an amide local anesthetic should be considered as an alternative.
Amides
Amide local anesthetics are less likely to cause allergic reactions than esters, as they do not produce PABA. However, their slower metabolism and reliance on liver function increase the potential for systemic toxicity, especially in patients with liver dysfunction or reduced hepatic blood flow, such as those with cirrhosis or congestive heart failure. In these cases, amides may lead to elevated blood levels and a higher risk of adverse effects, particularly with agents like bupivacaine, which has a longer duration of action.
Prilocaine has a unique toxicity profile because its metabolite, ortho toluidine, can cause methemoglobinemia, a condition in which the oxygen-carrying capacity of the blood is reduced. This condition can occur when prilocaine is administered in large doses, leading to clinical signs of cyanosis and respiratory distress. This is an important consideration in patients with certain underlying health conditions.
