This document discusses local anesthetics, including their classification, mechanism of action, pharmacokinetics, uses, and properties of an ideal local anesthetic. Specifically, it classifies local anesthetics based on their chemical structure as either esters or amides and describes the differences between the two. It explains how local anesthetics work by blocking sodium channels and nerve impulse conduction. The document also lists the desired learning objectives and properties students should understand about local anesthetics.

2. Learning objectives
At the end of the class the students should be able to:
• Classify the local anaesthetics based on the chemical and
special property
• Explain the mechanism of action , pharmacodynamics and
pharmacokinetics of local anaesthetics
• List the desired properties of an ideal local anaesthetic
• Mention factors that affect the action of local anaesthetic
• Differentiate between ester linked and amide linked local
anaesthetics
• Enlist the adverse effects and toxicity of local anaesthetics
• List the precautions and interactions related to local
anaesthetics

3. Local anaesthetics – drugs which upon topical
application or local injection causes reversible
loss of sensory perception, specially pain, in a
restricted area of the body
Blocks generation and conduction of nerve
impulse at all parts of neuron thus affects both
sensory & motor impulses
Difference between general & local anaesthetics?

4. The first clinically used Local Anesthetic
Cocaine (ISA activity)
A natural alkaloid from Erythroxylon coca.
Prototype Drug Lignocaine (Synthetic)

5. 1.CLASSIFICATION ACCORDING
TO CHEMISTRY
• ESTERS
 Cocaine
 Procaine
 Tetracaine
 Benzocaine
(Contd)

6. • AMIDES
 Lignocaine/Lidocaine
 Bupivacaine
Levobupivacaine
Mepivacaine
 Prilocaine
 Etidocaine
 Ropivacaine

7. Chemistry
 LAs – weak bases with amphiphilic property
 A hydrophilic secondary or tertiary amine on one side & a
lipophilic aromatic residue on other side joined by an alkyl
chain through an ester or amide linkage
 Ester linked LAs – Cocaine, Procaine, Chlorprocaine,
Tetracaine, Benzocaine
 Amide linked Las – Lignocaine, Bupivacaine,
Dibucaine, Prilocaine, Ropivacaine

9. ANESTHETICS

10. Features amide LAs
 More intense and longer lasting anaesthesia
 Bind to α1 acid glycoprotein
 Not hydrolyzed by plasma Esterases
 Hypersensitivity rare. No cross sensitivity with other
LAs
Features of ester linked LAs
 Short duration, less intense analgesia
 High risk of hypersensitivity
 Rarely used for infiltration or nerve block
 Still used on mucous membrane

11. 2.According to Duration of action
Short Duration of Action
Procaine
Medium Duration of Action
Cocaine, Lidocaine, Mepivacaine, Prilocaine
Long Duration of Action
Tetracaine, Bupivacaine, Etidocaine, Ropivacaine

12. 3. CLASSIFICATION ACCORDING
TO CLINCIAL USES
• SURFACE ANESTHESIA
 Tetracaine
 Lignocaine
 Cocaine
 Benzocaine
 INFILTRA
TIONANESTHESIA & FIELD
BLOCKANESTHESIA
Lignocaine
Procaine
Bupivacaine

13. • NERVE BLOCK ANESTHESIA
 Procaine
 Lignocaine
 Bupivacaine
 Tetracaine
 Ropivacaine

14. • SPINALANESTHESIA
 Lignocaine
 Tetracaine
 Bupivacaine
 EPIDURALANESTHESIA
Lignocaine
Bupivacaine
 ANESTHETIC USED IN OPHTHALMOLOGY
Proparacaine, Lignocaine

15. • Potency =lipid solubility
• Higher solubility =can use a
lower concentration and reduce
potential for toxicity
Anesthetic Potency

16. MECHANISM OF ACTION
• Diffusion into the nerve fiber
• Blockade of sodium channels

17. Thres
Poten
hold
tial
Resting Membrane
Potential
Na+ equilibrium
Action
Depolarization!
Hyperpolarized
Potential
+ 40 mv
Na+ influx K+ efflux

19. Progressively increasing conc. of a LA applied
to a nerve fiber produce blockade of more & more
Na+ channels :
• The threshold for excitation increases
• Impulse conduction slows
• The rate of rise of AP declines
• The AP amplitude decreases
• Finally the ability to generate an AP is abolished

20. SUSCEPTIBILITY OF NERVE
FIBER TO LA
 Potency
 Size of nerve fiber (small fibers blocked 1st)
 Effect of fiber diameter
 Rate of firing (rapidly firing fibers blocked
1st)
 Effect of fiber position in the nerve bundle
(outer fibers blocked 1st, then core fibers)

21.  Block sensory nerve endings, nerve trunks,
neuromuscular junction, ganglion synapse & receptors
 Injected around a nerve – anaesthesia of skin and
paralysis of voluntary muscle supplied by that nerve
 Smaller fibers – more sensitive than larger fibers
 Non myelinated fibers blocked more easily than
myelinated fibers
Local actions

22.  LAs enter the axon at nodes of Ranvier only
 Density of Na channels higher at these nodes
 Autonomic fibers more susceptible than somatic
fibers
 Order of somatic afferent blockade : Pain –
temperature – touch – deep pressure sense
Local actions (Contd…)

23. Addition of adrenaline (vasoconstrictor)
1:50,000 to 1:200,000
 Prolongs the duration of action of LAs
 Reduces systemic toxicity
 Makes injection more painful
 Provides a bloodless field of surgery
 Increases the chance of local tissue edema
 Necrosis & delayed wound healing
 Raise BP and promote arrhythmia

24. Systemic actions
CNS
 Stimulation followed by depression
 Cocaine –powerful stimulant
 Procaine –less potent
 Lignocaine – drowsiness and lethargy. Higher doses –
excitation followed by depression
 Basic action – neuronal inhibition
 Apparent stimulation due to inhibition of inhibitory
neurons

25. CVS
 Cardiac depression
 Decrease automaticity, excitability, contractility,
conductivity and increased ERP
 Quinidine –like antiarrhythmic action
 Procaine –procainamide –prolongation of QTc interval
 Bupivacaine – relatively more cardiotoxic
 Lignocaine – little effect on contractility and
conductivity

26.  Fall in BP due to sympathetic blockade
 Cocaine –sympathomimetic property, ↑ BP & tachycardia
Blood vessels

27.  Surface anaesthetic rapidly absorbed from mucous
membranes and abraded areas
 Absorption from intact skin - poor
 Rate of absorption depends on blood flow to area of
application or injection
 Ester LAs hydrolyzed by plasma pseudo
cholinesterase
 Amide Las – degraded in liver microsomes by
dealkylation and hydrolysis
 Oral procaine & lignocaine- high first pass metabolism
Pharmacokinetics

28. Relative
lipid
solubility
Relative
potency
onset pKa Local
duration
vasodilation Plasma
protein
binding
procaine 1 1 slow 8.9 short +++ 5%
lidocaine 4 4 rapid 7.9 moderat
e
+++ 55%
tetracaine 80 16 slow 8.5 long + 75%
bupivacain
e
130 16 slow 8.1 long + 90%
Plasma protein binding may be used as an indirect measure of tissue binding tendencies

29. ♣ CNS-lightheadedness, dizziness, visual disturbance,
mental confusion, disorientation
♣ CVS- bradycardia, hypotension, arrhythmias, vascular
collapse
♣ Local –painful injections, with vasoconstrictors more
tissue damage,
♣ Bupivacaine –highest local tissue irritancy
♣ Preservative in chlorprocaine – neurological
complications
♣ Hypersensitivity reactions- rashes, angioedema,
dermatitis, asthma. Cross reactivity more with ester
LAs
Adverse effects

30. Prevention of Toxicity
 Enquire about history of allergy.
 Caution in presence of liver/myocardial damage.
 Proper site (correct knowledge of nerve course).
 Minimal effective dose usage (avoid I/V adm).
 Wait after injection.
 Observe the face for any twitching, excitement, and pulse
for tachycardia.
 Observe post – op for allergic reactions.
 Avoid food intake at least 04 hrs prior to anesthesia to
prevent vomiting.

31.  Surface anaesthesia
 Infiltration anaesthesia
 Conduction block
1. Field block
2. Nerve block
 Spinal anaesthesia
 Epidural anaesthesia
 Intravenous regional anaesthesia
(intravascular infiltration anaesthesia)
Uses & techniques of local anaesthesia

32. Properties Desirable in a Local
Anesthetic
• Non-irritating
• Do not cause permanent damage to nerve structure
• Systemic toxicity should be low
• Effective
Injected
Applied locally
• Onset of action as short as possible
• DOA long enough to allow time for counter plated surgery