This seminar discusses local anesthetics, including their definition, history, routes of administration, mechanism of action, and classification. Local anesthetics work by blocking nerve conduction and sensation of pain without affecting other body systems. The seminar traces the history of local anesthetics from their natural origins to modern synthetic versions like lidocaine. It also examines different routes of administration and how structural modifications can influence a drug's potency, duration, and toxicity. The seminar provides an overview of key topics relating to local anesthetic agents.

1. Seminar on
LOCAL ANAESTHETICS
PRESENTED BY
MR. MAHESH G. UMBARKAR
(B.PHARM VII TH SEM)
GUIDED BY
MS. R.A. INGLE
M. PHARM
Paramhansa Ramakrishna Maunibaba Shikshan Sanstha’s
ANURADHA COLLEGE OF PHARMACY

2. Contents
 Definition
 History
 Routes of Administration
 Mechanism of action
 Classification
 Structural Activity Relationship
 Reference

3. Definition
 Local anaesthetics agent are drug that, when given
either topically or administered directly into localised
area producing the state of local anaesthetics by
blocking the nerves conduction which conduct the
pain sensation.
 Does not affect the cardio-Respiratory function.
 These are used in dentistry , ophthalmology , insect
bite and burn also.
 Now a days dentist use ‘Nitrous oxide gas’.
 Side effect after withdrawal occur.

4. History
 Local anaesthetics use firstly originated from natural
source.
 As early as 1532-Coca leaves used Europe in Peru.
 1860- “Niemann”-obtained crystalline alkaloid from
coca leaves-Name- ‘cocaine’.
 1868- “Moreno y-maize”-cocaine local anaesthetics....
 1880-”Van Anrep”-Experiment on animals.
 1884-First successfully surgery on cocaine.

5. Routes of Administration
 Spinal cord- Firstly used in 1885 but not introduced
into clinical practice up to 1899 it observed side effect
such as “Postpunctural head act”.
 Epidural-Using epidural catheter developed in 1930
 This is a highly successful technique now a days.

6. • Topical-This technique is often used during
examination procedures involving the respiratory
track, eye and dental surgery.

7. Mechanism of Action

8.  Sensory nerve are called ‘Afferent nerve’.
 Motor nerve are called ‘Efferent nerve’.
 Both are called “peripheral nervous system”.
 Nerve fibre=Bundle of neurons.
 Sensory Transmition means physical impulses
converted into chemical one.
 In clinical practice, solution of local anaesthetics
except cocaine contain adrenalin, nor-adrenalin,
vasoconstrictor.

9.  Vasoconstrictor which are prolong the action and
lower the systemic toxicity due to lower absorption
into circulation.

10. Classification
A. Natural Agent-
 Cocaine:
 Cocaine is also known as “coke”.
 It is a strong stimulant mostly used as recreational drug.
 It is commonly inhaled as smoke, or dissolved and
injected into a vein.
 Mental effect may include loss of contact with reality, an
feeling of happiness.
 Physical symptomes may include a fast heart rate,
sweating and large pupils.
 High doses can result in very high blood pressure or body
temperature.

11. B. Ester local Anaesthetics-
 Procaine:
 First synthetic local anaesthetics.
 Now a days it is called as “Novacaine”. Procaine
 Procaine synthesised in 1904.
 Procaine are also added in penicilline-G injection to
reduce the pain during injection.
 It is not used in topically because of low lipid
solubility.

12. Chloroprocaine:
 The trade name of chloroprocaine is “Nesacaine”.
 It has short duration of action, hence large dose
required.
 It has rapid onset f action 3-5 min.
Chloroprocaine

13. Tetracaine-
 Addition of butyl side chain on para position increase
lipid solubility and use topically.
Tetracaine
 Over dose causes CNS toxicity, Hypersensativity.

14. Benzocaine-
 It used for Endoscopy, Bronchoscopy and in topical
spray.
Benzocaine
 Toxicity-higher dose-more than 200 to 300ml causes
“methemoglobinemia”.

15. C. Amino amide local anaesthetics:
 Lidocaine-
 It discovered in 1940-1948
 First modern local anaesthetics. Lidocaine
 Trade name- “Xylacaine”.
 When lidocaine are given with adrenaline, PH must
be 2-2.5 to prevent hydrolysis of adrenaline.
 The absorption decreases when with adrenaline.

16. Prilocaine-
 Discovered in 1959.
Prilocaine
 Used systemic local anaesthetics, because quick
metabolism.
 Shorter duration of action than lidocaine.
 Prilocaine may also be contraindicated in people
with sickle cell anaemia, anaemia.

17. Articaine-
 This drug was first synthesized by Rusching in 1969.
 It is the only local anaesthetic to contain a thiophene ring,
meaning it can be described as 'thiophenic'; this conveys
lipid solubility.
 In dentistry, articaine is used mainly for infiltration
injections.
Articaine

18. Structural Activity Relationship
1) LIPOPHILIC:
 The aryl radical is attached directly to carbonyl group
–lipophilicity increase.This play a important role to
bind local anaesthetics to channel receptar protain.

19. Placement of aryl group with substituent that increase
the electron density of carbonyl oxygen enhance
activity.
Structural modification leads to change in physical
and chemical property.
Electron withdrowing substitution in O and P position
increase activity.
Amino, alkyl amino, alkoxy group inhance electron
density in aromatic ring hence activity incease.

20. Substitution enhance zwitterion formation will be
more potent hence m- position decrease activity.
Tetracaine is more potent than procaine(40-50)times
due to presence of butyl group which increase lipid
solubility and also butyl group increase the formation
of zwitterions.
2)INTERMIDIATE:
In procaine series anaesthetics potency decrease in
following order-S>O>N.

21. Modification affect the duration of action and toxicity
such amide (X=N)more resistance to metabolic
hydrolysis than ester (X=O).Thioester (X=S) causes
dermatitis.
Placement of small alkyl group around ester group or
amide function which increase the duration of action.
3)HYDROPHILIC POSITION:
Amino alkyl group is not necessary for local
anaesthetic action but it is form water soluble salt such
as HCL salt.

22. Tertiary amine more useful, secondary amine has
largest duration of action but irritating, primary amine
have not active and shows irritation.
Local anaesthetics should have increase lipid solubility
and lower Pka value that leads to rapid onset of action
and lower toxicity.

23. Reference
1) Foy’s Principles of Medicinal Chemistry, Thomas L.
Lemko, David A. Williams , International edition,
Seventy edition, page no.-455-468
2) Textbook of Medicinal Chemistry by V. Algarswamy,
CBS Publication, Third edition , Volume-1 Page no.
150-180.
3) Wilson and Gisvold’s Textbook of Organic Medicinal
Chemistry, Twelfth edition, South Asian edition,
Page.no.-718-730.