Pharmaceutical Chemistry II D.Pharm

1. Pharmaceutical Chemistry II
LOCAL
ANAESTHETICS
Presented by
P.SOWMIYA
Assistant Professor
Dept. of Pharmaceutical chemistry
SVCP

2. Introduction
 Local anaesthetics are drugs which produce localized
insensitivity to pain when drugs applied topically or injected in
particular area so that pain is not sensed.
 Local anaesthetics act by blocking the transmission of nerve
impulses.
 They are reversible.
 There is no loss of consciousness
unlike general anaesthetics.

3. Classification of local anaesthetics
based on clinical uses
1. Surface anaesthesia
2.Infiltration anaesthesia
3.Nerve block anaesthesia
4.Spinal anaesthesia

4. Surface anaesthesia
• Surface anaesthetics have good penetrating power.
• So applied on the surfaces say skin or mucous membrane.
• They block sensory nerve impulses on these particular areas.
• Eg: Benzocaine
• cocaine
• lignocaine

5. Infiltration anaesthesia
• Infiltration anaesthesia are injected subcutaneously into the tissues
to reach nerve branches and terminals.
• Used primarily for minor surgical procedures such as suturing a
wound.
• Used in dental extractions.
• Eg: Procaine and Lignocaine
• Adrenaline is also given along with local aneasthetics to
vasoconstriction and thereby keep the drug at a site for longer
time.

6. Nerve block anaesthesia
• Nerve block anaesthesia are injected into the nerve plexus
(branching network) or nerve trunk.
• It paralyses particular regions of the body (shoulder and upper
arm).
• Eg: Procaine, Lignocaine, Bupivacaine

7. Spinal anaesthesia
• Spinal aesthesia are injected into the subarachnoid space around
the spinal cord.
• Eg: Lignocaine
• Bupivacaine

8. Classification based on Chemistry
Local Anaesthetics
ESTERS
Simple esters
Eg: Benzocaine
Amino esters
Eg: Procaine
AMIDES
Eg: Lignocaine

9. Structure Activity Relationship (SAR)
Structure of local anaesthetics consists of 3 parts
Lipophilic aromatic group
Intermediate chain
Hydrophilic amino group

11. LIPOPHILIC GROUP:
 To penetrate the lipid layer and reach the binding site on the inside of
the cell.
INTERMEDIATE:
• Increasing in chain length decreases the potency because they get
ionised outside membrane and thus can’t penetrate into binding site.
HYDROPHILIC GROUP:
 Amines will accept a proton and form positively charged quaternary
form which is essential for binding to voltage gated ion channels.

12. MECHANISM OF ACTION
Loss of pain/ senses
No conduction of impulses to
CNS
No generation of Action potential
No entry of Na ions into the cell
No depolarization
Block Voltage- Gated sodium channels
Local Anaesthetics

13. 1. BENZOCAINE
• NOMENCLATURE: ethyl-p-amino benzoate
• Ester of p-aminobenzoic acid and ethanol.
• Synthesis:
NH2
O
O
C
H3
NH2
O
O
H
+ C
H3
OH
NH2
O
O
C
H3
PABA Ethanol Benzocaine

14. PHYSICAL PROPERTIES
APPERANCE:
colourless crystals or white crystalline
powder
 odourless
SOLUBILITY:
 Very slightly soluble in water
 freely soluble in ethanol, chloroform and ether
 dissolves in dilute acids

15. CHEMICAL PROPERTIES
• DIAZOTISATION REACTION
Aromatic primary amino group + sodium nirite + Hydrochloric acid
Diazonium chloride + 2- Naphthol
Deep Red Azo Dye

16. • Benzocaine + HCl+ Iodine solution
Precipitate produced
• Distinguished from Procaine
Benzocaine + HCl+ Potassium mercuric Iodine solution
No precipitate

17. STABILITY:
• When Benzocaine is boiled with water, it is destroyed.
• Also decomposed by alkali hydroxides.
• Affected by light.
STORAGE:
 since it is affected by light, it is stored in well closed and light resistant
container.

18. USES:
 Local anaesthetic
 Used as dusting powder and ointment to relieve the pain in ulcers
and wounds.
 used to relieve pain after dental surgery
As Lozenges used for sore throat and stomatitis
FORMULATIONS:
 Ointment
 Gel
 Sprays
 Ear drops
 Lozenges

19. BRAND NAMES:
• Orasap
• Cepacol
• Mucocare
• Mucopain
• Vilowax

20. 2. PROCAINE
• NOMENCLATURE: 2-diethylaminoethyl-p-aminobenzoate
• Ester of p-aminobenzoic acid
NH2
O O
N
CH3
CH3

21. PHYSICAL PROPERTIES
APPEARANCE:
 White crystalline powder
 odourless
SOLUBILITY:
 Very soluble in water
 soluble in ethanol
 slightly soluble in chloroform
Practically insoluble in ether
MELTING POINT: 153-158 C

22. CHEMICAL PROPERTIES
• DIAZOTISATION REACTION
Aromatic primary amino group + sodium nirite + Hydrochloric acid
Diazonium chloride + 2- Naphthol
Deep Red Azo Dye
• Decolourises acidified potassium permanganate immediately

23. • Procaine + HNO3
Evaporated to dryness
Residue
Dissolved in acetone & add alcoholic potash
Brownish red colour

24. STABILITY:
• Stable at pH 3.6
• Affected by light
STORAGE:
 since it is affected by light, it is stored in well closed and light
resistant containers.

25. USES:
• Local Anaesthetic
• Widely used in dental surgery and for producing spinal anaesthesia
FORMULATION:
• Procaine injection, IP, BP
• Procaine and adrenaline injection, IP

26. BRAND NAMES:
• Novocaine
• Syntocaine
• Venocaine
• Ethocaine
• Topocaine

27. • Pro-Pen-G

28. 3. LIGNOCAINE (Lidocaine)
• NOMENCLATURE: N-diethylamino-2,6-
dimethylphenyl)acetamide
• It is an amide
• Contains Xylidine

29. PHYSICAL PROPERTIES
APPEARANCE:
 White crystalline powder
 odourless
TASTE:
• slightly bitter, numbing taste
SOLUBILITY:
 Freely soluble in Chloroform & ethanol
 Very soluble in water
Practically insoluble in ether
MELTING POINT: 74-79 °C

30. CHEMICAL PROPERTIES
1 ) Lignocaine + HNO3
Evaporated to dryness
Residue
Dissolved in acetone & add alcoholic potash
A green colour

31. 2) Aqueous solution of lignocaine + NaOH
Filter
Residue dissolved in alcohol & cobalt chloride solution
Bluish green precipitate
3) Lignocaine + Picric acid lignocaine picrate melts
at 229 °C

32. STABILITY AND STORAGE:
• Since it is stable in air, stored in well closed container.
Uses:
 Local anaesthetic – surface, nerve, infiltration and spinal
anaesthesia
Anti-arrythmias – intramuscular injection

33. FORMULATIONS:
• Lignocaine Hydrochloride Injection I.P, B.P
• Lignocaine Hydrochloride and Adrenaline Bitartrate Injection,
B.P
• Lignocaine and Dextrose Injection, I.P
• Lignocaine Hydrochloride Gel I.P, B.P
• Lignocaine and Chlorhexidine Gel, B.P
• Lignocaine cream

34. BRAND NAMES
•Xylocaine
•Lignoheal
•Lidocain
•Lidowell

35. Livlocaine-A