5.2 Local Anesthetic.pdf b pharm third year sem

The localised action of local anaesthetic s
B pharm medicine chemistry semister 5
North Maharashtra University pharmacy council of India ,

1. Pointtobecovered:
•SARofLAs
•Benzoicacidderivatives:Cocaine,Hexylcaine,Meprylcaine,Cyclomethycaine,
Piperocaine
•AminoBenzoicacidderivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
•Lidocaine/Anilidederivatives:Lidocaine,Mepivacaine,Prilocaine,Etidocaine
•Miscellaneous:Phenacaine,Diperodon,Dibucaine*
1Dr.Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
CHAPTER 5.2: LOCAL ANAESTHETICS

2. ▪Localanesthetics(LAs)aredrugswhichtemporarilyblocknervesignals,causinganumbing
effectinaspecificarea.
▪Theycanbeadministeredtopically(appliedtotheskinormucousmembranes)orthroughlocal
injectiontonumbtheareaaroundasurgicalsite,nerve,orothertargetedlocation.
▪Intheappliedareatheycausereversiblelossofsensoryperception,especiallyofpainby
blockingthegenerationandconductionofnerveimpulsewithintheneurons,withoutcausing
anystructuraldamage.
▪Theyinterruptedbothsensory&motorimpulse,resultinginmuscularparalysisandlossof
autonomiccontrolaswell.
▪Thisallowsforminorsurgicalprocedures,painrelief,andotherinterventionswithouttheneed
forgeneralanesthesia.
2Dr.Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
LOCALANESTHETICS

3. InjectableLAs:
▪Lowpotency,shortduration:Procaine,Chloroprocaine.
▪Intermediatepotencyandduration:Lidocaine(Lignocaine),Prilocaine.
▪Highpotency,longduration:Tetracaine(Amethocaine),Bupivacaine,Ropivacaine,Dibucaine
(Cinchocaine).
SurfaceLAs:
▪Soluble:Cocaine,Lidocaine,Tetracaine.
▪Insoluble:Benzocaine,Butyl-amino-benzoate,Oxethazaine.
3Dr.Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
CLASSIFICATION OF LOCAL ANESTHETICS

4. 4Dr.Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MECHANISM OF ACTION OF LOCAL ANESTHETICS

5. 5Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MECHANISM OF ACTION OF LOCAL ANESTHETICS

6. TheLAsbindwiththeLAreceptorlocatedatVoltagegatedNa+Channelandstabilizethe
channelorprolongationininactivatedstateandincreasethethresholdofchannelopeningand
furtherleadtodecreasingtheimpulseconduction.
ClinicalUses:
•Surfaceanesthesia
•Infiltrationanesthesia
•Conductionblock
•Spinalanesthesia
6Dr.Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MECHANISM OF ACTION OF LOCAL ANESTHETICS

7. ▪TheclinicallyusefulLAsareweakbaseswith
amphiphilicproperty.
▪Thebasiccomponentsinthestructureoflocal
anestheticsarethelipophilicaromaticportion
(abenzenering),anintermediatechain[either
esterlinkage(combinationofanaromaticacid
andanaminoalcohol)oramidelinkage
(combinationofanaromaticamineandan
aminoacid)],andthehydrophilicamine
portion.
7Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
CHEMISTRYOFLOCALANESTHETICS

8. A.Ester-linkedLAs:
Cocaine,Procaine,Chloroprocaine,Tetracaine,Benzocaine.
8Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
CHEMISTRYOFLOCALANESTHETICS
Benzocaine

9. B.Amide-linkedLAs:
Lidocaine,Bupivacaine,Prilocaine,Ropivacaine,Etidocaine,Mepivacaine,Dibucaine.
9Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
CHEMISTRYOFLOCALANESTHETICS
Dibucaine

10. A.AromaticRings
▪Aromaticringandsubstituentsatdifferent
positioninLAsmayaddlipophilicityand
enhancethepenetratingcapacity.
▪Substitutionatpara-positionofaromaticring
inestertypeLAsenhancetheabilityto
penetratethenervemembraneandincrease
theiraffinityatthereceptorsite.
10Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS

11. A.AromaticRings
▪Electrondonatingsubstitutionatpara-amino
(R-NH-Ar)likealkoxy(propoxycaine),
alkylamino(tetracaine)increasethepotency.
▪Becauseelectrondonatingsubstitutionenhance
theresonancebetweenAromaticring&
carbonylgroup&resultinginincreasethe
affinitytoreceptor.
11Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS

12. A.AromaticRings
▪Electronwithdrawingsubstitutiondecreasethe
electroncloudaroundthecarbonylgroupand
resultingindecreaseintheLAactivity.
12Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS

13. B.IntermediateLinker
▪Thelinkermaybecarbon,oxygen,nitrogen
containingfunctionmoietiesmajorlyesterand
amidelinkage.
13Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS

14. B.IntermediateLinker
▪Whenlengthofalkylchainoflinkerisincreased,
lipophilicity,proteinbinding,durationofaction
andtoxicitymayincrease.
▪Ester&amidelinkagehavesimilarbinding
affinity,butamidelinkagehasdifferedin:-
•Producemoreintenseandlongerlasting
anesthesia
•Bindtoalfa1acidglycoproteininplasma
•Nothydrolyzedbyplasmaesterase
•Rarelycausehypersensitivityreactions;no
crosssensitivitywithesterLAs
14Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS

15. B.IntermediateLinker
▪Branchingofalfa-carbonwillincreasethe
durationofactioninprocaineseriesbutlidocaine
seriesdoesnotshowthiseffects.
15Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS

16. C.Amino-alkylSubstitution
▪Amino-alkylgroupisimportantfordrugwater
solubilitynotessentialforactivity.E.g.
Benzocainehavenoamino-alkylsubstitution.
▪Tertiaryaminederivativearemorepotentand
lesstoxic.Whereassecondaryaminesmay
increasethedurationbuthavingirritativeaction
andprimaryaminesarenotsuitableduetoless
active&highlytoxic.
16Dr.Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
SAR OF LOCAL ANESTHETICS
Benzocaine

17. 1.BenzoicAcidDerivatives:Cocaine,Hexylcaine,Meprylcaine,Cyclomethycaine,Piperocaine
17Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
A)Cocaine:Cocaineisthemethylesterofbenzoylecgonine
Methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-
8-azabicyclo-octane-2-carboxylate
Uses
▪UsedasanLAintheinnerliningofmouth
duringoralsurgery,ophthalmology(4%
solution).
▪Ithasalsovasoconstrictorproperties,used
todecreasebleeding&swellingfromminor
injuries.

18. 1.BenzoicAcidDerivatives:Cocaine,Hexylcaine,Meprylcaine,Cyclomethycaine,Piperocaine
18Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
B)Hexylcaine:
1-(cyclohexylamino)propan-2-yl benzoate
Uses
▪HexylcaineactsashortactingLAusedinoral
surgery.
▪Itisusedassurfaceanesthesia(10-20%)and
topicalanesthesia.

19. 1.BenzoicAcidDerivatives:Cocaine,Hexylcaine,Meprylcaine,Cyclomethycaine,Piperocaine
19Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
C)Meprylcaine:
[2-methyl-2-(propylamino)propyl] benzoate
Uses
▪Itisusedindentistry(surface0.5%orinfiltration
anesthetics).
▪Itisusedastopicalanesthesia.
▪Usedinacutepainduetotrauma,surgery,
infectionetc.

20. 1.BenzoicAcidDerivatives:Cocaine,Hexylcaine,Meprylcaine,Cyclomethycaine,Piperocaine
20Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
D)Cyclomethycaine:
3-(2-methylpiperidin-1-yl)propyl 4-
cyclohexyloxy benzoate
Uses
▪Itisusedastopicalanesthesia(0.5-2%solution)in
minorsurgery.

21. 1.BenzoicAcidDerivatives:Cocaine,Hexylcaine,Meprylcaine,Cyclomethycaine,Piperocaine
21Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
E)Piperocaine:
3-(2-methylpiperidin-1-yl) propyl
benzoate
Uses
▪Itisusedassurfaceanesthesia(0.5%solution)in
ophthalmology,mouthulcer.
▪Usedindentistry.

22. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
22Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
A)Benzocaine:
ethyl 4-aminobenzoate
Uses
▪Usedassurfaceanesthesia.
▪Usedindentalpain,sorethroat.
▪10-20%,ineardrops,cream,ointment,sprays,etc.
foranalgesiaandtopicalanesthesia.

23. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
23Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
A)SynthesisofBenzocaine:

24. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
24Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
B)Butamben:
Butyl 4-aminobenzoate
Uses
▪Usedassurfaceanesthesiaforskinmucous
membrane.
▪Usedinchronicpain.

25. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
25Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
C)Procaine:
2-(diethylamino)ethyl 4-
aminobenzoate
Uses
▪UsedasInfiltrationanesthesia(0.25-0.5%
solution)
▪ForperipheralnerveblockdoseofprocaineHCl
is500mghasusedas0.5%in100ml.

26. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
26Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
C)Procaine:

27. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
27Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
D)Butacaine:
3-(dibutylamino)propyl
4-aminobenzoate
Uses
▪Usedassurfaceanesthesia.
▪Usedindentalpain,earandnasaldrops.

28. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
28Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
E)Propoxycaine:
2-(Diethylamino)ethyl 4-amino-
2-propoxybenzoate
Uses
▪Potentlong-actinglocalanesthetics.
▪Profoundanesthesiawheninjectedclosetonerve
sheath.

29. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate
29Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
F)Tetracaine(Amethocaine):
2-(dimethylamino)ethyl 4-
(butylamino)benzoate
Uses
▪Usedspinalandtopicalanesthesia.

30. 2.AminoBenzoicAcidDerivatives:Benzocaine*,Butamben,Procaine*,Butacaine,
Propoxycaine,Tetracaine,Benoxinate.
30Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
F)Benoxinate:
2-(diethylamino)ethyl-4-amino-
3-butoxybenzoate
Uses
▪Usedassurfaceanestheticagentandusedin
ophthalmology.

31. 3.Lidocaine/Anilidederivatives:Lidocaine,Mepivacaine,Prilocaine,Etidocaine
31Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
A)Lidocaine:
2-(diethylamino)-N-(2,6-
dimethylphenyl)acetamide
Uses
▪Lidocainehasarapidonsetofaction,usedas
infiltrationanesthesia(5-300mg).
▪1%solution-blockthesympatheticnerve.
▪50mg(5ml)-blockthecervicalnervesintheneck,
providingpainrelief.
▪Lidocainealsousedincardiacarrhythmia.

32. 3.Lidocaine/Anilidederivatives:Lidocaine,Mepivacaine,Prilocaine,Etidocaine
32Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
B)Mepivacaine:
N-(2,6-dimethylphenyl)-1-
methylpiperidine-2-carboxamide
Uses
▪Usedaslocalanesthesiaforanepiduralorspinal
blockanddentalprocedure.

33. 3.Lidocaine/Anilidederivatives:Lidocaine,Mepivacaine,Prilocaine,Etidocaine
33Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
C)Prilocaine:
N-(2-methylphenyl)-2-
(propylamino)propanamide
Uses
▪Usedasregionalanesthesia.
▪Usedtopicaladministrationtodecreasethepainful
needlesticksinchildren.

34. 3.Lidocaine/Anilidederivatives:Lidocaine,Mepivacaine,Prilocaine,Etidocaine
34Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
D)Etidocaine:
N-(2,6-dimethylphenyl)-2-
[ethyl(propyl)amino]butanamide
Uses
▪Usedforepiduralandtopicalanesthesia.
▪Usedforperipheralnerveorplexusblock.

35. 4.Misc.Drugs:Phenacaine,Diperodon,Dibucaine*
35Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
A)Phenacaine:
N,N'-bis(4-ethoxyphenyl)
ethanimidamide
Uses
▪1%solutionusedasLAforocularoperation
▪1-3%solutionusedtotreatmentofskinoperative
procedure,dentalandotherminorsurgery.

36. 4.Misc.Drugs:Phenacaine,Diperodon,Dibucaine*
36Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
B)Diperodon:
[2-(phenylcarbamoyloxy)-3-piperidin-1-
ylpropyl]-N-phenylcarbamate
Uses
▪Usedtotopicalanesthesiaforskinanalgesiaand
minorsurgeryofskin.
▪Usedtonerveblock.
▪Usedtotreatmentoffoot,andankledisorders.

37. 4.Misc.Drugs:Phenacaine,Diperodon,Dibucaine*
37Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
C)Dibucaine:
2-butoxy-N-[2-(diethylamino)
ethyl]quinoline-4-carboxamide
Uses
▪Usedassurfaceanesthesia.
▪Usedtoreliefpainanditching.
▪Usedtoreduceswelling.

38. 4.Misc.Drugs:Phenacaine,Diperodon,Dibucaine*
38Dr. Rahul Pawara (M. Pharm., Ph.D.) RCPIOP Shirpur
MEDICINAL CHEMISTRY OF LOCAL ANESTHETICS
C)Dibucaine: