DIBUCAINE NUMBER

By Dr.SANDEEP

DIBUCAINE NUMBER

• The Dibucaine Number is a measure of the qualitative activity of Pseudo cholinesterase and is the percentage of inhibition of the enzyme by the local anesthetic Dibucaine.

• It is used to differentiate individuals who have substitution mutations of the Butryl cholinesterase enzyme

DIBUCAINE

• Dibucaine (cinchocaine), is an amino amide L.A.

• It was commonly used for central neuraxial anesthesia.

• When administered to humans i.v , it is capable of inhibiting the plasma Pseudocholinesterase enzyme.

• This tetrameric enzyme is responsible for the metabolism of a number of substances including amino ester local anaesthetics and Succinylcholine

Pseudo cholinesterase/ Butyrylcholinesterase

• Synthesis-liver

• Converts Succinylcholine to Succinylmonocholine and choline

• The activity of the enzyme refers to the number of substrate molecules (micromoles) hydrolysed per unit of time, often expressed in international units (IU)

• Dibucaine inhibits its normal activity.

SUCCINYLCHOLINE

• Depolarizing neuromuscular blocker.

• Composed of two molecules of acetylcholine linked back to back through the acetate methyl groups.

• Like Ach, stimulates cholinergic receptors at the NMJ, nicotinic and muscarinic autonomic sites.

• Rapid onset of effect and ultra short duration of action

• ED95 is 0.51 to 0.63 mg/kg.

• Administration of 1mg/kg of Sch results in complete suppression of neuromuscular stimulation in approximately 60 seconds.

• In patients with normal Butrylcholinesterase, recovery of 90% muscle strength requires 9 to 13 min

• Metabolised to Succinylmonocholine and then to succinic acid and choline.

• Elimination t ½ is 47 sec

• Reduced Butyrylcholinesterase activity may occur as a

result of

inherited causes

acquired causes.

INHERITED CAUSES

• In the inherited type, an individual receives a gene

from each parent, one of which may be the wild type

Butyrylcholinesterase, or the mutant.

• Some mutations will slow or completely deactivate

the enzyme's ability to catalyze the breakdown of Sch

• Inherited reductions occur due to mutations at a

single autosomal location on the long arm of

chromosome 3

• At least one substitution is capable of altering the

efficiency of enzymatic catalysis.

• A point mutation has been identified that changes

Asp-70 to Gly in the atypical form of serum

cholinesterase, leading to reduced affinity of

atypical cholinesterase for choline esters.

• It can be Homozygous typical

Heterozygous atypical

Homozygous atypical

ACQUIRED CAUSES

PEOPLE SUCH AS

• Elderly • pregnant• Infants• Parturition

and certain other physiologic conditions have low Pseudocholinesterase enzyme levels.

ACQUIRED CAUSES

PATHOLOGIC STATES• Liver diseases• Malnutrition,• burns,• malignancy• Uremia• O.P. poisoning• Chronic infections• Hypothroidism• Collagen vascular

diseases

DRUGS• Oral contraceptives• MAOI• Anticholinesterase drugs• Tetrahydroaminacrine• Hexafluorenium• Metocllopramide• Bambuterol(prodrug of

terbutaline)• Esmolol• Cytotoxic drugs• Ecothiphate

• The Dibucaine Number is used to differentiate

individuals who have substitution mutations of the

butrylcholinesterase enzyme

• The extent of the catalysis can be determined by

measuring % of Sch that remains unchanged in

the blood after a standard dose of Dibucaine

inhibition challenge which has been established

as the DIBUCAINE NUMBER TEST.

• Typical measurement of Dibucane number yields

values of

80 and above for wild type homozygotes

(normal),

40-60 for heterozygotes (atypical),

20 or less for atypical homozygotes.

TYPE OF BUTRYLCHOLINESTERASE

GENOTYPE INCIDENCE DIBUCAINE NUMBER

RESPONSE TO SCH OR

MIVACURIUM

HOMOZYGOUS TYPICAL

E1uE1u NORMAL NORMAL NORMAL

HETEROZYGOUS ATYPICAL

E1uE1a 1/480 50-60 LENGTHENED BY 50%-

100%

HOMOZYGOUS ATYPICAL

E1aE1a 1/3200 20-30 PROLONGED BY 4-8 HRS

• The distinctive quality of Dibucaine is that its

enzyme inhibition of the wild type

Butyrylcholinesterase (Typical) is substantially

greater than that of the mutant

Butyrylcholinesterase (Atypical).

• Thus, the atypical enzyme is said to be resistant

to Dibucaine inhibition.

IMPORTANCE • When enzyme activity is reduced, there is an increase

in the duration of the neuromuscular blockade - which may necessitates the unnecessary post op mechanical ventilation due to prolonged neuromuscular blockade

• But, in most of the cases, there is only mild increase in the duration of the apnea

Eg:- Decrease to 20% of normal activity by severe liver disease, the duration of apnoea, increases from a normal duration of 3 minutes to just 9 minutes