Local Anesthetic Agents
Integrated Medicinal Chemistry and
Pharmacology II
PSC 6311
Karen S. Mark
,
Ph.D.
; Associate Professor Pharmaceutical Sciences
Office:
Room 275
email:
[email protected]
ph:
865-288-5839
Katzung,
Basic and Clinical Pharmacology
, 14
th
ed.; Chapter 26
Foye’s,
Principles of Medicinal Chemistry
, 8
th
ed.; Chapter 12
Foye’s,
Principles of Medicinal Chemistry
, 7
th
ed.; Chapter 16
Goodman & Gilman’s
The Pharmacological Basis of Therapeutics
, 13
th
ed.;
Chapter 22
Lecture Objectives
1.Identify which nerves transmit pain sensation 2.Describe the chemical classes of local anesthetics and the mechanism of action3.List signs and symptoms of local anesthetic side effects and toxicity 4.Describe the reason(s) for adding epinephrine to local anesthetic therapy5.Explain the impact of injecting a local anesthetic agent into an abscess/wound 6.Explain the properties that determine potency, onset and duration of action
Local Anesthetic Drugs Covered
in this Section
Ester-type
Benzocaine
Cocaine
Procaine
Tetracaine
Amide-type
Articaine
Bupivacaine
Lidocaine
Mepivicaine
Prilocaine
Ropivacaine
Introduction
Local anesthetics
block
initiation & conduction of APs
on nerves
causing sensory & motor paralysis
in localized area
Advantages
Reversible action at clinical conc.
Complete recovery in nerve fxn
Requires minimal equipment
Minimal systemic effects
Effective anesthesia to nerve region
Reduces need (or amt) for opioids to control pain
Disadvantages
Requires compliant patient
May require use of sedation
Possible systemic effects
Pain Nerve Transmission
Nerve Classification
Note
:
C and Aδ fibers
are responsible
for conducting
pain; thus,
targets for
analgesia/
sedation/ and
anesthesia
C fibers
(smallest)
transmit the
slow burning
pain,
unmylenated
A δ fibers
transmit the
fast pain
signals,
smallest,
mylenated
Aδ are thinnest
Fiber
Classifi-
cation
Anatomic
Myelin
Diameter
(μm)
Conduction
velocity
(m/sec)
Function
Sensitivity
to block
A fibers
A-alpha
(
a
)
Afferent to /
efferent from
muscles & joints
Yes
6-22
10-85
Motor &
proprioception
+
A-beta (
b
)
Yes
++
A-gamma
(
g
)
Efferent to
muscle spindles
Yes
3-6
15-35
Muscle tone
++
A-Delta (
d
)
Sensory roots;
afferent
peripheral nerves
Yes
1-4
5-25
Pain, temperature,
touch
+++
B fibers
Preganglionic
sympathetic
Yes
<3
3-15
Vasomotor,
visceromotor,
sudomotor, pilomotor
++++
C fibers
Postganglionic
sympathetic
No
0.3-1.3
0.7-1.3
Vasomotor,
visceromotor,
sudomotor, pilomotor
++++
Sensory dorsal
root; afferent
peripheral nerves
No
0.4-1.2
0.1-2
Pain, temperature,
touch
++++
Clinical Uses –
Local Anesthetics
Topical anesthesia
cornea (opthalmologist), mouth
Infiltration anesthesia
minor surgery (e.g. dental practice, tissue biopsy)
Field block, nerve block anesthesia
Spinal and epidural anaesthesia
blockade of pain via spinal nerves during labor or as
part of major surgery
Typical Injection
Sites for Spinal
Anesthesia Using
Local Anesthetic
Agents
Na
+
Channel Subunit / Blockade
Puffer fish
Clams & Mussels
Dart frog
natural teratotoxins bind at external site
local anesthetics bind at internal site
Local Anesthetic Drugs - MOA
