Local Anesthetics SAR

Dr. Monika Singh (Pharmaceutical
Chemistry)
02-09-2020
Medicinal CHEMISTRY-II (BP-501T) 1
LOCAL
ANESTHETICS
Dr. Monika Singh
(M.Pharm, PhD)
Unit V
Syllabus as per PCI
 Local Anesthetics: SAR of Local anesthetics.
 Benzoic Acid derivatives; Cocaine, Hexylcaine,
Meprylcaine, Cyclomethycaine, Piperocaine.
 Amino Benzoic acid derivatives: Benzocaine*,
Butamben, Procaine*, Butacaine, Propoxycaine,
Tetracaine, Benoxinate.
 Lidocaine/Anilide derivatives: Lignocaine,
Mepivacaine, Prilocaine, Etidocaine.
 Miscellaneous: Phenacaine, Diperodon, Dibucaine.*

Chemistry)
02-09-2020
Local Anesthetics
DEFINITION
 Drugs which
– produce a REVERSIBLE loss of sensation …
– in a localized part of the body…..
– when applied directly onto nerve tissues or
mucous membranes
LOSS OF PAIN WITHOUT LOSS OF
CONCIOUSSNESS
 Local anesthetics are ‘local’ ONLY because
of how they are administered! (Selectivity)
The first clinically used Local Anesthetic
Cocaine
A natural alkaloid from Erythroxylon coca.
Lignocaine (Synthetic)

Chemistry)
02-09-2020
Properties Desirable in a Local
Anesthetic
 Non-irritating
 Do not cause permanent damage to nerve structure
 Systemic toxicity should be low
 Effective
Injected
Applied locally
 Onset of action as short as possible
 DOA long enough to allow time for counter plated surgery
• Local anesthetics are weak bases – proportion of free
base (R-NH2 ) and salt (R-NH3
+ ) forms depends on pH
and pK of amino group
• Both free base and ionized forms of local
anesthetic are necessary for activity: local anesthetic
enters nerve fibre as neutral free base and the cationic
form blocks conduction by interacting at inner surface of
the Na+ channel

Chemistry)
02-09-2020
MECHANISM OF ACTION
(MOA)
 Blockade of
sodium channels
 Blockade of
Action potential /
Impulse generation

Chemistry)
02-09-2020
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
ORDER OF BLOCKADE
 AUTONOMIC
 PAIN
 TEMPERATURE
 TOUCH
 DEEP PRESSURE
 MOTOR
Recovery in reverse order

Chemistry)
02-09-2020
CHEMICAL CLASSIFICATION
according to chemistry
 ESTERS :
 A) Benzoic acid derivatives: Cocaine, Hexylcaine,
Meprylcaine, Cyclomethycaine, Piperocaine.
 B)Amino Benzoic acid derivatives: Benzocaine*,
Butamben, Procaine*, Butacaine, Propoxycaine,
Tetracaine, Benoxinate.
 AMIDES / Lidocaine/Anilide derivatives:
Lignocaine, Mepivacaine, Prilocaine, Etidocaine.
 Miscellaneous: Phenacaine, Diperodon,
Dibucaine.*
(Contd)
 ESTERS: A) Benzoic acid derivatives:
 Cocaine
Hexylcaine
 Piperocaine
2-methoxy carbonyl tropan-3-yl benzoate
• cause dependance
• Used as surface anesthetic
• A toxic action on heart may
induce rapid and lethal cardiac
failure.
• short acting LA
• Overdose can lead to headache,
tinnitus, numbness and tingling
around the mouth and tongue,
convulsions, inability to
breathe and decreased heart
function.
• as a local or spinal anesthetic
and in dental anesthesia.

Chemistry)
02-09-2020
 ESTERS: A) Benzoic acid derivatives:
Meprylcaine
Cyclomethycaine
Has stimulant properties
• also known as Epirocaine and
Oracaine
• Meprylcaine has a relatively
potent inhibitory action on the
monoamine transporter and
inhibits the reuptake of dopamine,
norepinephrine and serotonin.
Cycloalkyl ether moiety
4-(cyclohexoxy)benzoic acid 3-(2-
methyl-1-piperidinyl)propyl ester
• Long DOA
 ESTERS- B)Amino Benzoic acid derivatives:
 Benzocaine
Butemben
 Butacaine
Ethyl 4-amino benzoate
• Used for infiltration
• 20% in ear drops ,ointments, lotions
or gels
n-butyl 4-amino benzoate
•Used as surface anesthetic
•3-(dibutylamino)propyl 4-amino
benzoate
• Used as surface anesthesia
• Butacaine is used to treat burns
that have become infected.

Chemistry)
02-09-2020
 ESTERS- B)Amino Benzoic acid derivatives:
Procaine
 Propoxycaine
Benoxinate (Oxybuprocaine)
2-(diethyl amino ethyl) 4-amino benzoate
• parentrally (onset 2-5 min)
•DOA = 1hr
• 80% metabolize to give PABA
•It is Vasodilator
• more potent and toxic than
lidocaine
• Used for dentistry (0.4%)
•parenterally (onset 2-5 min)
•Used as surface anesthetic
• opthalmic soln , 0.5% - topical
anesthesia of
the cornea and conjunctiva.
•Withdrawn from US market in
1996
• 0.4% in short ophthalmic
procedures
R
 ESTERS
Tetracaine
2-(dimethyl amino) ethyl 4-
(butylamino) benzoate
(0.25 to 1.0 %)
•Used for spinal anesthesia
(0.5% sol)
2-(Dimethylamino)ethyl 4-(butylamino)benzoate
2-(Dimethylamino)ethyl 4-(butylamino)benzoate

Chemistry)
02-09-2020
 AMIDES /ANILIDES/ LIGNOCAINE
derivatives:
 Lignocaine (Lidocaine)
2- diethyl amino – 2`,6`-dimethyl acetanilide
Or
2- diethyl amino aceto– 2`,6`-xylidide
• Absorbed from GIT and mucus
membrane
• metabolize in liver to give MEGX
( monoethyl glycine xylidide and
GX (glycine xylidide)
• Used as surface anesthetic (fot
UTIs)/ parentrally for infiltration
• Effective by all routes.
• Faster onset, more intense, longer
lasting, than procaine.
• Good alternative for those allergic
to ester type
• Also used as antiarrthmic agent
Effective within 5 min
Duration of Action – 1-1.5 h, pka=7.8
 AMIDES
 Mepivacaine
Bupivacaine

•Used for infiltration
and nerve block
anesthesia
• used IV or Epidural
(Not for topical use)
•Toxic to neonates
• Used for infiltration and
nerve block anesthesia
• More cardiotoxic than other LA
• Slower onset and one of the
longer duration agents (6-8hrs),
pka=
• Not for topical use
•Used for infiltration and nerve
block anesthesia
•

Chemistry)
02-09-2020
 AMIDES
 Prilocaine
Etidocaine
• given by injection during
surgical procedures and labor
and delivery.
• it has a long DOA
• main disadvantage of using
during dentistry is increased
bleeding during surgery.
Cream (lidocaine
2.5% and
prilocaine 2.5%),
applied to intact
skin under
occlusive dressing,
provides dermal
analgesia
 Miscelaneous
 Diperodon
 Phenacaine
 Dibucaine
(aminodicarbonate type)
•Used as for surface
anesthesia
• As ointment
(amidine type)
•Used as for surface
anesthesia
• for eye
a quinoline derivative
and amino amide
used on the skin to stop
itching and pain from
certain skin conditions
(such as scrapes, minor
burns, eczema, insect
bites)

Chemistry)
02-09-2020
Applications of local anesthesia:
• Nerve block: injected locally to produce regional
anesthesia (e.g., dental and other minor surgical
procedures)
• Topical application: to skin for analgesia (e.g.,
benzocaine) or mucous membranes (for diagnostic
procedures)
• Spinal anesthesia: injection into CSF to produce
anesthesia for major surgery (e.g., abdomen) or
childbirth
• Local injection: at end of surgery to produce long-
lasting post-surgical analgesia (reduces need for
narcotics)
• I.V infusion: for control of cardiac arrhythmias
(e.g., lidocaine for ventricular arrhythmias)
Chemistry
Most local anesthetics consist of 3 parts
1. Lipophilic Aromatic group
2. Intermediate chain
3. Hydrophilic Amino group

Chemistry)
02-09-2020
C
LAs - Weak Bases (pKa:7.5-9)
C O
O
R N
R
R
NH
O
R N
R
R
Aromatic portion Amine portion
Intermediate chain
ESTER
AMIDE
LIPOPHILIC HYDROPHILIC
PHARMACOKINETICS
Combination with vasoconstrictors
(resultant reduction in blood flow reduces rate
of systemic absorption & diminishes peak
serum levels)
Distribution
 Biotransformation & Excretion

Chemistry)
02-09-2020
ADVERSE EFFECTS
 CNS (1st stimulation, then depression)
 Local Neurotoxicity
 CVS (bupivacaine – most cardiotoxic)
 ANS
 Motor Paralysis
 Hematological Effects
 Hypersensitivity reactions
THANKS

Local Anesthetics SAR

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

More from Monika Singh

More from Monika Singh (8)

Recently uploaded

Recently uploaded (20)

Local Anesthetics SAR