Cholinesterases pseudocholinesterase

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

This enzyme [EC 3.1.1.8] (also known as cholinesterase, pseudocholinesterase, acylcholine acylhydrolase, nonspecific cholinesterase, and benzoylcholinesterase) catalyzes the hydrolysis of an acylcholine to generate choline and a carboxylic acid anion. A variety of choline esters and a few other compounds can serve as substrates. 

Succinylcholine is a neuromuscular blocking agent, which is used clinically to cause muscle relaxation. Its duration of action is short due to rapid metabolism—hydrolysis by cholinesterases (pseudocholinesterase or acylcholine acyl hydrolase)—in the plasma and liver to yield inactive products (Fig. 7.55). Thus, the pharmacological action is terminated by the metabolism. However, in some patients, the effect is excessive, with prolonged muscle relaxation and apnea lasting as long as two hours compared with the normal duration of a few minutes. 

Plasma or serum cholinesterase (pseudocholinesterase) is inhibited by a munber of compounds and can also be decreased in ftie presence of liver impairment. Erythrocyte cholinesterase (true cholinesterase) reflects more accurately the cholinesterase status of the central nervous system. However, pseudocholinesterase activity responds more quickly to an inhibitor and returns to normal more rapidly than eiythrocyte-cholinesterase activity. Thus, measurement of pseudocholinesterase activity is quite adequate as a means of diagnosing acute exposure to organophosphorus compounds, but cases of illness which may be due to chronic exposure to these compounds should also be investigated by determining the erydirocyte-cholinesterase activity. A colorimetric method for this purpose has been reported (K.-B. Augustinsson et ah, Clinica chim. Acta, 1978, 89, 239-252). 

L23. Lehmann, H., and Liddell, J., Human cholinesterase (pseudocholinesterase) Genetic variants and their recognition. Br. J. Anaesth. 41, 235-244 (1969). 

V2. Van Ros, G., and Druet, R., Uncommon electrophoretic patterns of serum cholinesterase (pseudocholinesterase). Nature (London) 212, 543-544 (1966). 

Carboxylesterases include cholinesterase (pseudocholinesterase), arylcarboxyesterases, liver microsomal carboxylesterases, and other unclassified liver carboxylesterases. Cholinesterase hydrolyzes oholihe-like esters (succinylcholine) and procaine as well as acetylsalicylic acid. Genetic variant forms of cholinesterase have beeh idehtified in human serum (e.g., succinylcholine toxicity when administered as ganglionic blocker for muscle relaxation). Meperidine is hydrolyzed only by liver microsomal carboxylesterases (Fig. 10.19). Diphenoxylate is hydrolyzed to its active metabolite, diphenoxylic acid, within 1 hour (Fig. 10.19). Presumably, the peripheral pharmacological action of diphenoxylate is attributed to zwitterionic diphenoxylic acid, which is readily eliminated in the urine. 

A study of 16 patients who had been taking various beta blockers (propranolol 5, atenolol 5, metoprolol 2, bisoprolol 2, oxprenolol 1, celiprolol 1) for longer than one month found no difference in the onset and duration of action of rocuronium, when compared with a control group. Similarly, intra-operative esmolol did not affect the onset and recovery time from suxamethonium (succinylcholine) blockade in patients with normal plasma cholinesterase (pseudocholinesterase) activity, but see also (b) above. 

Suxamethonium is metabolised in the body by plasma cholinesterase. Ecothiopate iodide depresses the levels of this enzyme so that the metabolism of the suxamethonium is reduced and its effects are thereby enhanced and prolonged. One study in 71 patients found that two drops of ecothiopate iodide 0.06% three times a week in each eye caused a twofold reduction in plasma cholinesterase (pseudocholinesterase) activity in about one-third of the patients, and a fourfold reduction in 1 in 7 patients. ... 

Not understood. Studies with human plasma failed to find any evidence that cimetidine in therapeutic concentrations inhibits the metabolism of suxamethonium. However, metoclopramide may do and therefore is possibly the drug responsible for any interaction seen. In vitro studies with very high cimetidine concentrations found inhibition of plasma cholinesterase (pseudocholinesterase) activity. The cimetidine/vecuro-nium interaction is not understood, but it has been suggested that cimetidine may reduce the hepatic metabolism of vecuronium. ... 

Two patients, one taking phenelzine and the other who had eeased to do so 6 days previously, developed apnoea following ECT during whieh suxamethonium (succinylcholine) was used. Both responded to injeetions of nikethamide and positive pressure ventilation with oxygen. A later study observed the same response in another patient taking phenelzine. This would appear to be explained by the finding that phenelzine eaused a re-duetion in the levels of plasma cholinesterase (pseudocholinesterase) in 4... 

Normal plasma cholinesterase (pseudocholinesterase) is 80% inhibited by the anaesthetic dibucaine, i.e. it has a dibucaine number of 80. In individuals with suxamethonium sensitivity, the cholinesterase differs from the normal form and is less susceptible to dibucaine inhibition, i.e. it has lower dibucaine numbers. This enzyme behaviour is used in phenotyping members of an affected family, since heterozygotes have dibucaine numbers intermediate between those of normals and homozygotes. 

---