Procaine acid hydrolysis

Dmgs that contain ester linkages include acetylsalicylic acid (aspirin), physostigmine, methyldopate, tetracaine and procaine. Ester hydrolysis is usually a bimolecular reaction involving acyl-oxygen cleavage. For example, the hydrolysis of procaine is shown in Scheme 4.2. 

Hydrolysis. Hydrolysis of esters and amides is a common pathway of drug metabolism. The liver microsomes contain non-specific esterases, as do other tissues and plasma. Hydrolysis of an ester results in the formation of an alcohol and an acid hydrolysis of an amide results in the formation of an amine and an acid. The ester procaine, a local anaesthetic, is rapidly hydrolysed by plasma cholinesterases and, to a lesser extent, by hepatic microsomal esterase. An example of an amide which is hydrolysed, is the antiarrhythmic drug procainamide. Enalapril, a prodrug, is hydrolysed by esterases to the active metabolite enalapri-late, which inhibits the angiotensin-converting enzyme. 

Specific Local Anesthetic Agents. Clinically used local anesthetics and the methods of appHcation are summarized in Table 5. Procaine hydrochloride [51-05-8] (Novocain), introduced in 1905, is a relatively weak anesthetic having along onset and short duration of action. Its primary use is in infiltration anesthesia and differential spinal blocks. The low potency and low systemic toxicity result from rapid hydrolysis. The 4-arninobenzoic acid... 

The metabolic degradation of local anesthetics depends on whether the compound has an ester or an amide linkage. Esters are extensively and rapidly metabolized in plasma by pseudochoUnesterase, whereas the amide linkage is resistant to hydrolysis. The rate of local anesthetic hydrolysis is important, since slow biotransformation may lead to drug accumulation and toxicity. In patients with atypical plasma cholinesterase, the use of ester-linked compounds, such as chloroprocaine, procaine and tetracaine, has an increased potential for toxicity. The hydrolysis of all ester-linked local anesthetics leads to the formation of paraaminobenzoic acid (PABA), which is known to be allergenic. Therefore, some people have allergic reactions to the ester class of local anesthetics. 

Another good example of hydrolysis reaction is the anesthetic procaine, which is prone to specific acid-catalyzed decomposition (of the protonated form) at a pH value below 2.5, a specific base-catalyzed hydrolysis between pH 5.5 and 8.5, titration around pH 8.5-11.0 and finally, the base-catalyzed hydrolysis of the free base at a pH value above 12.0. Maximum stability occurs at pH 3.5. 

In this biotransformation B is the product of a Phase I reaction and is less active than A. An example would be the hydrolysis of the local anesthetic procaine (A) to j -aminobenzoic acid (B). 

Procaine (novocain), the first synthetic local anesthetic, is an amino ester (see Figure 14-1) with low potency, slow onset, and short duration of action. Its use now is confined to infiltration anesthesia and occasionally for diagnostic nerve blocks. Its hydrolysis in vivo produces para-aminobenzoic acid which inhibits the action of sulfonamides. Thus, large doses should not be administered to patients taking sulfonamide drugs. 

Both components in Procaine-penicilUn can be determined using nitrous acid.< > When the samples are hydrolysed, both hydrolysis products, penillo-aldehyde and penicillamine, most likely undergo nitrosation. If hydrolysis is not carried out, Procaine forms a diazotate, the wave of which is measured. 

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