Bupivacaine elimination

Ester and amide local anaesthetics differ in the manner, site and rate of metabolism. There is little relation between the elimination of local anaesthetics and their duration of action. Amethocaine has a prolonged action due to its high affinity for nerve tissue despite being rapidly removed from plasma. Bupivacaine can be detected in the plasma many hours after its effects have worn off due to continuing absorption from the site of injection. The renal excretion of unchanged local anaesthetics is minimal. 

Of all the local anaesthetics available, levobupivacaine and ropivacaine have the most favourable pharmacological characteristics for use in obstetrics. They have the lowest potential for cardiotoxicity and, unlike lidocaine and prilocaine, there is little risk of cumulation when they are administered by epidural infusion at effective doses. Elimination of all amides is prolonged in the neonate, exceeding 20 h in the case of bupivacaine. 

Bupivacaine-induced cardiotoxicity, notably after epidural use, is a matter of concern and controversy (1-3). The risk can be greatly reduced or eliminated by careful dosage and/or the use of lower concentrations (SEDA-12,108) (1). 

Ropivacaine is an amide-type LA, a vasoconstrictor at less than 1% and a vasodilator at more than 1%. The fact that it is the pure S-enantiomer reduces its toxicity. Like phenol, it is metabolized by the liver and eliminated by the kidneys. When administered by dermal injection, it has a rapid onset of action (less than a minute) and the duration of action is longer than or equal to that of bupivacaine. Combining it with adrenaline does not prolong its duration of action, and a concentration of 0.75% provides longer anesthesia than a concentration of 1%. Neurological and cardiovascular tolerance to ropivacaine is much better than to bupivacaine. What is more, there is a considerable difference between the neurotoxic and cardiotoxic doses. The toxicity of ropivacaine is intermediate between that of lidocaine and bupivacaine. Direct intravascular injection of ropivacaine is still dangerous, however. 

Metabolism of ester local anesthetics is carried out by plasma cholinesterases and may be rapid. Procaine and chloroprocaine have half-lives of only 1-2 minutes. The amides are hydrolyzed in the liver and have half-lives from 1.8 hours to 6 hours. Bupivacaine and ropiva-caine are very lipid-soluble and long-acting local anesthetics. Liver dysfunction may increase the elimination half-life of amide local anesthetics. 

Noble DW, Smith KJ, Dundas CR. Effects of H-2 antagonists on tiie elimination of bupivacaine. BrJAnaes i (1987) 59, 735-7. 

Good relationships between the retention in MLC and some biological activities of local anesthetics (bupivacaine, lidocaine, mepiva-caine, prilocaine, procaine and tetracaine), such as anesthetic potency, concentration of compound that produces an effect similar to a reference concentration of cocaine, duration of the action, toxicity and time taken to eliminate half the drug present in the body, have also b n reported [24]. Some anesthetic actions of barbiturates also correlated well with the retention minimum effective hypnotic dose in rabbits, molar drug concentration necessary to reduce cell division, and molar drug concentration required to reduce 50% the inhibition of oxygen respiration on the brain of a rat in vitro [25],... 

Metabolic pathways/drug clearance and elimination bupivacaine is bound to plasma proteins in varying degree. It undergoes hepatic metabolism (via conjugation with glucuronic acid) and renal excretion (4-10% unchanged). 

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