Dibucaine resistant pseudocholinesterase

Table 2. Frequency Distribution of the Allele FOR Dibucaine-Resistant Pseudocholinesterase in Various Populations...

The most common mutant is the so-called dibucaine-resistant enzyme variant. It is characterized principally by its reduced afiSnity for a series of substrates and inhibitors as compared with the normal pseudocholinesterase. Although at high concentrations succinyldicholine can also be converted by the dibucaine-resistant enzyme variant, the absence of enzymatic hydrolysis under pharmacologic conditions is adequately explained by the large difference in the Michaelis constants of succinyldicholine with the normal enzyme with the dibucaine-resistant variant Usually the variant is identified by the reduced inhibition of its reaction with the substrate benzoylcholine produced by the local anaesthetic dibucaine (cinchocaine). The percentage of inhibition by dibucaine under standard conditions, defined as the dibucaine number (DN). is about 20 for the dibucaine-resistant variant and app oximately 80 for the ordinary enzyme. Serum activity from heterozygotes having both enzymes is inhibited about 40-70%. 

The second so-called fluoride-resistant variant is similarly differentiated from the normal and dibucaine-resistant enzymes by its different sensitivity to the pseudocholinesterase inhibitor NaF. 

This is an example of generic variation in drug metabolism Pseudocholinesterase in this patient is resistant to the inhibitory action of dibucaine The problem is not due to inadequate activity of acetylcholinesterase Neostigmine should be administered to establish the nature of the problem... 

Cholinesterase inhibitors (eg, neostigmine) markedly prolong the neuromuscular blockade caused by succinylcholine. They increase ACh at the end plate, which intensifies depolarization, and they also inhibit succinylcholine metabolism by pseudocholinesterase. About one in 500 persons have a single abnormal gene for pseudochoUnesterase. Fewer than one in 3000 persons have two abnormal genes (homozygous atypical) that produce an enzyme with only 1% of the normal affinity for succinylcholine. The atypical enzyme is resistant to the inhibitory action of dibucaine. The answer is (E). 

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