Dibucaine number

1. DIBUCAINE NUMBER By Dr.SANDEEP

2. 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

3. 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

4. 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 .

5. 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 .

6. 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

7. Reduced Butyrylcholinesterase activity may occur as a result of inherited causes acquired causes .

8. 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

9. 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

10. ACQUIRED CAUSES PEOPLE SUCH AS Elderly pregnant Infants Parturition and certain other physiologic conditions have low Pseudocholinesterase enzyme levels.

11. 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

12. 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.

13. 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.

14. 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

15. 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.

16. 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