Chloroprocaine Other names: Nesacaine

Chloroprocaine, is an ester-type local anaesthetic. Chloroprocaine, blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the action potential.

The onset of action for spinal administration is very rapid (9.6 min ± 7.3 min at 40 mg dose; 7.9 min ± 6.0 min at 50 mg dose) and the duration of anaesthesia may be up to 100 minutes.

The onset of action for perineural administration is very rapid (6 to 12 min) and the duration of anaesthesia may be up to 100 minutes. Patients with a successful block without any supplementation in the first 45 minutes after readiness for surgery are 90.8% with chloroprocaine HCl.

Absorption and Distribution

The plasma concentration should be negligible for intrathecal use.

Biotransformation

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. This process could be decelerated in case of pseudocholinesterase deficiency.

The hydrolysis of chloroprocaine results in the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid.

The in vitro plasma half-life of chloroprocaine in adults is 21 ± 2 seconds for males and 25 ± 1 seconds for females. The in vitro plasma half-life in neonates is 43 ± 2 seconds. In women, plasma half-lives in vivo of 3.1 ± 1.6 minutes was measured.

Elimination

The metabolites, ßdiethylaminoethanol and 2-chloro-4-aminobenzoic acid, are excreted by the kidney into the urine.

Pharmacokinetic in spine

Elimination of chloroprocaine from the CSF is entirely by diffusion and vascular absorption, either in neural tissues in the intrathecal space or by crossing the dura along the concentration gradient between CSF and the epidural space. Consequently, chloroprocaine is subject to vascular absorption. The predominant factors determining the rate of absorption are local blood flow and competing binding to local tissues, but not enzymatic hydrolysis in the CSF. In patients with cholinesterase deficiency it is reasonable to expect very low peak plasma levels of chloroprocaine after intrathecal injection. Clearance of chloroprocaine from CSF by diffusion across the dura into the epidural space and subsequent systemic absorption may not be impaired to a clinically significant degree.

Adverse effects in non-clinical studies, were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

No studies in animals to evaluate carcinogenic potential and reproductive and developmental toxicity have been conducted with chloroprocaine.

In vitro genotoxicity studies didn’t provide evidence for 2-chloroprocaine and 4-amino-2-chlorobenzoic acid (main metabolite) to have a relevant mutagenic or clastogenic potential.