Local anesthetics are drugs that cause reversible loss of sensation in a localized area of the body when applied to nerve tissues or mucous membranes. They work by reversibly blocking sodium ion channels, preventing the generation and conduction of nerve impulses. Common local anesthetics include lidocaine, bupivacaine, benzocaine, and procaine. They are classified based on their chemistry (ester or amide linkage) and duration of action. Local anesthetics can be administered via various techniques like infiltration, nerve block, spinal block, for procedures, surgeries and pain management in a localized region of the body.

1. Local Anaesthetics
SUJIT KARPE
PRINCIPAL,
SOJAR COLLEGE OF PHARMACY, KHANDVI

2. Local anaesthetics
• Drugs which
• produce a REVERSIBLE loss of sensation …
• in a localized part of the body…..
• when applied directly onto nerve tissues or mucous
membranes
• Local anesthetics are ‘local’ ONLY because of how they
are administered! (Selectivity)

3. • L.A. reversibly block impulse conduction along nerve axons
and other excitable membrane.
• A local anesthetic is a drug that causes reversible local
anesthesia and a loss of nociception. When it is used on
specific nerve pathways (nerve block), effects such as
analgesia (loss of pain sensation) and paralysis (loss of
muscle power) can be achieved.
Local anaesthetics

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

6. CLASSIFICATION ACCORDING TO CHEMISTRY

7. 2. According to Duration of action

9. Chemistry
Most local anesthetics consist
of 3 parts
1. Lipophilic Aromatic group
2. Intermediate chain
3. Hydrophilic Amino group

10. Two types of linkages give rise to 2 chemical classes of local
anesthetics.
ESTER LINKAGE AMIDE LINKAGE
PROCAINE
procaine (Novocaine)
tetracaine (Pontocaine)
benzocaine
cocaine
LIDOCAINE
lidocaine (Xylocaine)
mepivacaine (Carbocaine)
bupivacaine (Marcaine)
etidocaine (Duranest)
ropivacaine (Naropin)

12. + +
- -
+ +
--
- -
+ + + +
- -
Na+
+ ++ +
- - - -
Resting
(Closed**)
Open
(brief)
inactivated
Very slow
repolarization in
presence of LA
LA receptor
LA have highest
affinity for the
inactivated form
Refractory period
**Closed state may exist in various forms as it moves from resting to open. LA have a
high affinity for the different closed forms and may prevent them from opening.
MECHANISM OF ACTION

13. 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
MECHANISM OF ACTION

14. 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)

15. ORDER OF BLOCKADE
 AUTONOMIC
 PAIN
 TEMPERATURE
 TOUCH
 DEEP PRESSURE
 MOTOR
Recovery in reverse order

16. Effect on CNS
 CNS depression with initially stimulant action
Anxiety, apprehension, nervousness, confusion are
main toxic symptoms.
Followed by sedation, unconsciousness and
respiratory failure.

17. Effect on CVS
 high systemic concentration may cause cardiovascular
effects.
Cause direct myocardiac depression and arterial vasodilation
 bradycardia, tachyarrhythmia, hypotension and cardiac
arrest may occur.

18. PHARMACOKINETICS
• Absorption
Dosage
Site of injection
(when used for major conduction blocks, the peak serum levels will
vary as a function of the specific site of injection, with intercostal
blocks among the highest, & sciatic & femoral among the lowest)
Lipid solubility
(more lipid soluble – longer DOA)

19. Ph
Vascularity
(highly vascular area – more rapid absorption – higher blood
levels)
Combination with vasoconstrictors (resultant reduction in
blood flow reduces rate of systemic absorption & diminishes
peak serum levels)
PHARMACOKINETICS

20. Comparison of LA characteristics
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 modera
te
+++ 55%
tetracain
e
80 16 slow 8.5 long + 75%
bupivacai
ne
130 16 slow 8.1 long + 90%
Plasma protein binding may be used as an indirect measure of tissue binding tendencies

21. ADVERSE EFFECTS
 CNS (1st stimulation, then depression)
 Local Neurotoxicity (cauda equina syndrome
associated with continuous spinal anesthesia – CSA)
 CVS (bupivacaine – most cardiotoxic)
 ANS
 Motor Paralysis
 Hematological Effects
 Hypersensitivity reactions

22. • Cocaine
• Medical use limited to surface or topical anesthesia
• Avoid epinephrine because cocaine already has
vasoconstrictor properties. (EXCEPTION!!!)
• A toxic action on heart may induce rapid and lethal
cardiac failure.
• A marked pyrexia is associated with cocaine overdose.

23. • LIDOCAINE (Xylocaine) Most widely used LA
• Effective by all routes.
• Faster onset, more intense, longer lasting, than
procaine.
• Good alternative for those allergic to ester type
• More potent than procaine but about equal toxicity
• More sedative than others

24. • Benzocaine
• pKa ~ 3,
• Available in many preps for relief of pain and
irritation
• for surface anesthesia (topical) only ... ointments,
sprays, etc.
• Used to produce anesthesia of mucous membranes
• methemoglobinemia

25. • Procaine
• Ester of PABA.
• Poorly lipid soluble
• It has to be injected so no value as a surface anaesthetic
• Commonly administered with adrenaline
• Has muscle relaxant and quinidine like action.
• Less toxic than cocaine
• Mainly used for infiltration and conduction anaesthesia

26. Techniques and applications of LA

27. Topical / Surface anaesthesia

28. Nerve block Field block Local infiltration

30. Techniques and applications of LA
I. Topical / Surface anaesthesia:
 used in the form of ointment, cream, powder and directly
applied to the site which is to be anaesthetized.
Contraindicated for application to mucous membrane.
 Application –
• reduce pain, itching of ulcers, fissures and hemorrhoids.
• Anaesthetize corneal surface, mucosa of mouth, nose, pharynx,
larynx and urethra.
Drugs: Lignocaine, Amethocaine

32. Techniques and applications of LA
II. Infiltration anaesthesia:
 Anaesthesia is produced by injecting anaesthetic agent through
out the area.
In this nerve ending are anaesthetized by their direct exposure.
 Application –
• used for minor operations like removal of cyst.
Drugs: Lignocaine, Procaine

33. Nerve block anaesthesia

34. Techniques and applications of LA
III. Nerve block anaesthesia:
 in this either drug is injected in the surrounding area of that part
which is to be operated, or deposited close to the mixed nerves
like redial, ulnar, palantine etc.
Is called as field block anaesthesia.
Drugs: Lignocaine, Procaine

36. Techniques and applications of LA
IV. Spinal anaesthesia:
 drug is injected into subarachnoid space.
After administration drug reaches to spinal nerve and dorsal root
of ganglia
Drug is injected at the site to block roots of those nerve which
innervate area to be operated.
Position of patient play important role in restricting anaesthesia
to desired level.
Duration of spinal anaesthesia can be increased by addition of
0.2ml of 1:1000 solution of adrenaline.

37. Techniques and applications of LA
 Applications –
 In obstetrics.
 In gynecological surgery.
Drug: Lignocaine