local anaesthesia

1. Local
Anaesthesia
PRESENTED BY- DR NEHA SHARMA
MODERATED BY-DR LHAMO DOLMA

2. Contents
• History
• Molecular structure
•Classification
•Mechanism of action
•Characteristics
•Pharmacokinetics
•Uses
•LAST
•REFERENCES

3. History
1.KARL KOLLER introduced COCAINE as the first local anaesthetic in
OPHTHALMOLOGY in 1884
2.First synthetic local anaesthetic was PROCAINE
3.Lidocaine was synthesized by LOFGREN in 1943

4. Molecular Structure
Consists of hydrophilic and lipophilic portion separated by a
connecting hydrocarbon chain
Esters
Amides

5. ESTERS
PROCAINE
CHLOROPROCAINE
TETRACAINE
AMIDES
LIDOCAINE
PRILOCAINE
MEPIVACAINE
BUPIVACAINE
LEVOBUPIVACAINE
ROPIVACAINE
Classification

7. Mechanism of
Action
1. Site of action : voltage gated
Na+ channels.
2. Inhibits passage of sodium ions
through ion –selective sodium
channels in nerve membranes
thus prevents transmission of
nerve impulses (conduction
blockade)
3. Thereby reducing excitability of
neuronal, cardiac or CNS tissue.

9. MINIMUM EFFECTIVE
CONCENTRATION (Cm)
Minimum concentration of drug necessary to produce conduction
blockade of nerve impulses
Factors affecting Cm
1. Increases with increase in Nerve diameter (Cm of motor fiber is 2x
sensory fiber)
2. Decreases with increase in tissue Ph & nerve stimulation

10. Characteristics
• Colourless liquids.
• weak bases
• pk values just above physiologic pH
• Intrinsic vasodilator

11. DRUGS
PROCAINE
LIDOCAINE
BUPIVACAIN
E
LEVOBUPI-
VACAINE
ROPIVACAIN
E
POTENCY
1
1
4
4
4
ONSET
Slow
RAPID
SLOW
SLOW
SLOW
Pk
8.9
7.9
8.1
8.1
8.1
PROTEIN
BINDING
%
6
70
95
>97
94
LIPID
SOLUBILITY
0.6
2.9
28
VOLUME
OF
DISTRIBUT
ION(L)
65
91
73
55
59
CLEARANCE(L
/MIN)
0.95
0.47
0.44

12. Physiochemical structures
1. The S enantiomers of bupivacaine and mepivacaine are less toxic
than racemic mixture of these LA present commercially
2. Whereas Ropivacaine and Levobupivacaine developed as pure S
enantiomers commercially are less toxic than racemic mixtures or R
enantiomer

13. Alkalinization
• Shortens onset of neural blockade, enhances sensory and neural
blockade, increases epidural blockade
• increases % of LA in lipid soluble form that is available to diffuse
across lipid cellular barriers
• hence, adding sodium bicarbonate increases speed of onset of
peripheral nerve block

14. Pharmacokinetics
•Absorption
•Distribution
•Metabolism
•Excretion

15. Absorption
1. MUCOUS MEMBRANE- faster due to weak barrier to LA
penetration, rapid onset of action (eg per rectal )
INTACT SKIN- high concentration of lipid soluble LA to ensure
analgesia ( EMLA for venous cannulation )

16. Systemic Absorption
1.Site of injection : rate of systemic absorption is directly
proportional to vascularity of site of injection :
intravenous>tracheal>intercostal>caudal>paracervical>epidural>
brachial plexus>sciatic>subcutaneous.
2.Presence of vasoconstrictors : addition of epinephrine
/phenylephrine increases neuronal uptake, enhances quality of
analgesia ,prolongs duration of action & limits toxic side effects.

17. Distribution
1.TISSUE PERFUSION- highly perfused tissue take up more drugs
2.TISSUE/BLOOD PARTITION COEFFICIENT- strong plasma protein
binding tends to retain anaesthetic in the blood whereas high lipid
solubility facilitates tissue uptake.
3.TISSUE MASS- more the mass, more is the reservation of LA

18. Metabolism and Excretion
1. Esters : hydrolysed by pseudocholinesterases
water soluble metabolites are excreted in the urine
2. Amides : metabolized by cytochrome P-450 enzymes in liver
Metabolism slower than esters hydrolysis . Metabolites are cleared
through urine.

19. Uses
1. Topical Anaesthesia : EMLA(eutectic mixture of local anaesthesia)
2. Local Infiltration
3. Peripheral nerve block
4. Intravenous Regional Anaesthesia (BIER’S BLOCK)
5. Epidural Block
6. Spinal Anaesthesia
7. Tumescent Liposuction

20. Doses
Drugs
Mepivacaine
Bupivacaine
Ropivacaine
Levobupivacaine
Minor block
50 to 200 mg
12.5 to 100 mg
10 to 100 mg
----------------
Major block
350 to 500 mg
175 to 225 mg
200 to 250 mg
200 to 225 mg
Spinal block
40 to 80mg
15 to 20 mg
(isobaric and
hyperbaric )
15 to 20 (isobaric
and hyperbaric )
15 to 20 mg
(isobaric and
hyperbaric )
Epidural block
350 to 500mg
175 to 225 mg
200 to 250mg
200 to 250 mg

21. Toxic Dose limit
Toxic dose limit:
Ropivacaine , bupivacaine : 2-3mg/kg
Lidocaine : 4-5 mg/kg
Lidocaine with epinephrine : 5-6 mg/kg

22. Allergic Reactions
1. Allergic reaction with LA is rare.
2. Allergic reaction is due to ester metabolites p amino benzoic acid
3. preservatives like methylparaben structural similarity to p amino
benzoic acid hence result in allergic reaction

23. LAST( local anaesthetic systemic
toxicity)
• It is due to excess plasma concentration of the drug.
• Plasma concentration is determined by rate of drug entrance into systemic
circulation
• Magnitude of systemic absorption depends on :
1. Doses of drug
2. Vascularity of injection site
3. Presence of vasoconstrictor
4. Physiochemical properties of drug

24. CNS Toxicity
EARLY- circumoral numbness, tongue paresthesia, dizziness, tinnitus,
blurred vision.
excitatory signs (restlessness, agitation, nervousness ,paronia)
precedes depression(slurred speech, drowsiness, unconsciousness)
LATE- tonic clonic seizure, respiratory arrest.

25. Cardiovascular Toxicity
Depresses myocardial contractility and conduction
velocity in higher doses.
Bradycardia, heart block, hypotension may culminate
into cardiac arrest.

27. Treatment of
LAST

28. References
1. MILLER’S ANAESTHESIA 9TH EDITION
2. STOELTING’S PHARMACOLOGY AND PHYSIOLOGY IN ANAESTHETIC PRACTICE
5TH EDITION
3.CLINICAL ANAESTHESIOLOGY MORGAN MIKHAIL MURRAY 4TH EDITION

29. THANK YOU