Local anaesthetics

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 r eversible . There is no loss of consciousness unlike general anaesthetics.

3. Classification of local anaesthetics based on clinical uses Surface anaesthesia Infiltration anaesthesia Nerve block anaesthesia 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

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

10. 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.

11. MECHANISM OF ACTION

12. 1. BENZOCAINE NOMENCLATURE: ethyl- p- amino benzoate Ester of p-aminobenzoic acid and ethanol. Synthesis:

13. 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

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

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

16. 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.

17. 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

18. BRAND NAMES: Orasap Cepacol Mucocare Mucopain Vilowax

19. 2. PROCAINE NOMENCLATURE: 2-diethylaminoethyl-p-aminobenzoate Ester of p-aminobenzoic acid

20. 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

21. 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

22. Procaine + HNO 3 Evaporated to dryness Residue Dissolved in acetone & add alcoholic potash Brownish red colour

23. 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.

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

25. BRAND NAMES: Novocaine Syntocaine Venocaine Ethocaine Topocaine

26. Pro-Pen-G

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

28. 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

29. CHEMICAL PROPERTIES 1 ) Lignocaine + HNO 3 Evaporated to dryness Residue Dissolved in acetone & add alcoholic potash A green colour

30. 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

31. 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

32. 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

33. BRAND NAMES Xylocaine Lignoheal Lidocain Lidowell

34. Livlocaine -A