LOCAL ANESTHETICS
By
S. Bohlooli, PhD
School of Medicine, Ardabil University of Medical Sciences
INTRODUCTION
HISTORY
Cocaine, the first local anesthetic introduced into
medical practice, was isolated by Niemann in
1860
 Procaine was synthesized by Einhorn in 1905
 Lidocaine, which is still a widely used local
anesthetic, was synthesized in 1943 by Löfgren.

BASIC PHARMACOLOGY OF
LOCAL ANESTHETICS
CHEMISTRY: STRUCTURE ESTER
Cocaine
Tetracaine (Pontocaine)
Procaine (Novocain)
Benzocaine
CHEMISTRY: STRUCTURE AMIDES
Lidocaine (Xylocaine)
Bupivacaine; Levobupivacaine
Mepivacaine
Ropivacaine (Naropin)
CHEMISTRY
Local anesthetics are weak bases
 the pKa of most local anesthetics is in the range
of 8.0–9.0
 Cationic form is the most active form
 The uncharged form is important for rapid
penetration of biologic membranes

PHARMACOKINETICS
Local anesthetics are usually administered by
injection into dermis and soft tissues around
nerves
 Absorption and distribution are not as important

ABSORPTION

Systemic absorption of injected local anesthetic
depends on:






Dosage
Site of injection
Drug-tissue binding
Local tissue blood flow
Use of vasoconstrictors (eg, epinephrine)
Physicochemical properties of the drug
DISTRIBUTION, METABOLISM AND EXCRETION
The amide local anesthetics are widely
distributed after intravenous bolus
administration
 The local anesthetics are converted in the liver
(amide type) or in plasma (ester type) to more
water-soluble metabolites
 Decreased hepatic elimination of local
anesthetics would be anticipated in patients with
reduced hepatic blood flow or hepatic diseases

PHARMACODYNAMICS: MECHANISM OF ACTION
PHARMACODYNAMICS

The function of sodium channels can be disrupted
in several ways:

batrachotoxin, aconitine, veratridine


tetrodotoxin (TTX) and saxitoxin


bind to receptors within the channel and prevent
inactivation
block sodium channels by binding to channel receptors near
the extracellular surface
Spinal neurons can be differentiated on the basis
of tetrodotoxin effect into:
TTX-sensitive
 TTX-resistant neurons

PHARMACODYNAMICS

With increasing concentrations of a local
anesthetic






The threshold for excitation increases
Impulse conduction slows
The rate of rise of the action potential declines
The action potential amplitude decreases
The ability to generate an action potential is
completely abolished
These effects result from binding of the local
anesthetic to more and more sodium channels
EFFECT OF EXTRA CELLURAR IONS

Increase in extracellular calcium partially
antagonizes the action of local anesthetics
Owing to the calcium-induced increase in the surface
potential on the membrane.
Increases in extracellular potassium enhancing the
effect of local anesthetics.:
 Depolarize the membrane potential and favor the
inactivated state.


RELATIVE SIZE AND SUSCEPTIBILITY OF DIFFERENT TYPES OF NERVE
FIBERS TO LOCAL ANESTHETICS
Fiber Type
Function
Diameter (m)
Myelination
Conduction
Velocity (m/s)
Sensitivity to
Block
Type A
Alpha
Proprioception, motor
12–20
Heavy
70–120
+
Beta
Touch, pressure
5–12
Heavy
30–70
++
Gamma
Muscle spindles
3–6
Heavy
15–30
++
Delta
Pain, temperature
2–5
Heavy
5–25
+++
Preganglionic autonomic
<3
Light
3–15
++++
Type C
Dorsal root
Pain
0.4–1.2
None
0.5–2.3
++++
Sympathetic
Postganglionic
0.3–1.3
None
0.7–2.3
++++
Type B
NERVE FIBERS DIFFER SIGNIFICANTLY IN
THEIR SUSCEPTIBILITY
Effect of Fiber Diameter
 Effect of Firing Frequency
 Effect of Fiber Position in the Nerve Bundle
 Effects on Other Excitable Membranes

CLINICAL PHARMACOLOGY OF
LOCAL ANESTHETICS
CLINICAL PHARMACOLOGY
Can provide highly effective analgesia in welldefined regions of the body
 The usual routes of administration






Topical application
Injection in the vicinity of peripheral nerve endings
(perineural infiltration)
Injection in the vicinity of major nerve trunks
(blocks)
Injection into the epidural or subarachnoid spaces
surrounding the spinal cord
Intravenous regional anesthesia (Bier block)
Schematic diagram
of the typical sites
of injection of local
anesthetics in and
around the spinal
canal
THE CHOICE OF LOCAL ANESTHETIC

The choice of local anesthetic is usually based on
the duration of action required

Short-acting:


Intermediate duration :


Procaine and chloroprocaine
lidocaine, mepivacaine, and prilocaine
long-acting :

tetracaine, bupivacaine, levobupivacaine, and ropivacaine
SOME TIPS
The onset of local anesthesia can be accelerated
by the addition of sodium bicarbonate
 Repeated injections of local anesthetics can result
in loss of effectiveness
 Pregnancy appears to increase susceptibility to
local anesthetic toxicity

TOXICITY
Central Nervous System
 Neurotoxicity



Cardiovascular System


Bupivacaine
Hematologic Effects


Lidociaine
Prilocaine: metabolite o-toluidine
Allergic Reactions

The ester-type local anesthetics: p-aminobenzoic acid
derivatives