Local Anesthetics

Sona Pradhan
July 3, 2009
2009
 Local Anesthetic
A local anesthetic is an agent that
interrupts pain impulses in a specific
region of the body without a loss of
patient consciousness. Normally, the
process is completely reversible--the
agent does not produce any residual
effect on the nerve fiber.
 History
 The first local anesthetic was Cocaine which
was isolated from coca leaves by Albert
Niemann in Germany in the 1860s. The very
first clinical use of Cocaine was in 1884 by
Sigmund Freud who used it to wean a patient
from morphine addiction. It was Freud and
his colleague Karl Kollar who first noticed its
anesthetic effect. Kollar first introduced it to
clinical ophthalmology as a topical ocular
anesthetic. Also in 1884, Dr. William Stewart
Halsted was the first to describe the injection
of cocaine into a sensory nerve trunk to
create surgical anesthesia.
 Chemistry
All local anesthetics are weak bases,
classified as tertiary amines.
Esters:
 These include cocaine, procaine,
tetracaine, and chloroprocaine.
 They are hydrolyzed in plasma by
pseudo-cholinesterase. One of the
by-products of metabolism is
paraaminobenzoic acid, the common
cause of allergic reactions seen with
these agents
Amides:
 These include lidocaine, mepivicaine,
prilocaine, bupivacaine, and
etidocaine.
 They are metabolized in the liver to
inactive agents. True allergic
reactions are rare (especially with
lidocaine)
 Mechanism of Action
 Local anesthetics work to block nerve
conduction by reducing the influx of sodium
ions into the nerve cytoplasm.
 Sodium ions cannot flow into the neuron,
thus the potassium ions cannot flow out,
thereby inhibiting the depolarization of the
nerve.
 If this process can be inhibited for just a
few Nodes of Ranvier along the way, then
nerve impulses generated downstream
from the blocked nodes cannot propagate
to the ganglion.
 Mechanism of action
 local anesthetics bind directly to the
intracellular voltage-dependent
sodium channels
 Block primarily open and inactive
sodium channels, at specific sites
within the channel
 Mechanism of action
 1) slow rate of depolarization
 2) reduce height of action potential

 3) reduce rate of rise of action potential

 4) slow axonal conduction

 5) ultimately prevent propagation of action

potential
 6) do not alter resting membrane potential

 7) increase threshold potential

 Factors affecting
local anesthetic action

Effect of pH
 charged (cationic) form binds to
receptor site uncharged form
penetrates membrane ,efficacy of
drug can be changed by altering
extracellular or intracellular pH
 Effect of lipophilicity
ANESTHETIC POTENCY
 Lipid solubility appears to be the primary
determinant of intrinsic anesthetic potency.
Chemical compounds which are highly
lipophilic tend to penetrate the nerve
membrane more easily, such that less
molecules are required for conduction
blockade resulting in enhanced potency.
 more lipophilic agents are more potent
as local anesthetics
 Effect of protein binding - increased
binding increases duration of action
 Effect of diffusibility - increased
diffusibility = decreased time of
onset
 Effect of vasodilator activity - greater
vasodilator activity = decreased
potency and decreased duration of
action
 FIBER SIZE AND FUNCTION
 α: (dia 12-20um; cond vel 70-120m/s)
largest, afferent to and efferent from
muscles and joints. Actions: motor
function, proprioception, reflex activity.
 β: (dia 5-12um; 30-70m/s) large as A-
alpha, afferent to and efferent from
muscles and joints. Actions: motor
proprioception, touch, pressure, touch and
pressure.
 γ: (dia 3-6um; 15-30m/s) muscle spindle
tone.
 δ: (dia 2-5um; 12-30m/s) thinnest, pain
and temperature. Signal tissue damage.
B fibers: (dia – 2-5um) Myelinated
preganglionic autonomic. Innervate
vascular smooth muscle. Though
myelinated, they are more readily
blocked by LA than C fibers.
C fibers: (dia 0.4-1.2 um)
Nonmyelinated, very small nerves.
Smallest nerve fibers, slow
transmission. Transmit dull pain and
temperature, post-ganglionic
autonomic.
* Both A-d and C fibers transmit pain
and are blocked by the same
concentration of LA.
 Susceptibility to block by local
anesthetics of types of nerve fibers
 In
general, small nerve fibers are
more susceptible than large fibers;
however,
– the type of fiber
– degree of myelination
– fiber length and
– frequency- dependence are also
important in determining susceptibility
Order of sensory function block
 1. pain
 2. cold
 3. warmth
 4. touch
 5. deep pressure
 6. motor

Recovery in reverse order

 TOXICITIES OF LOCAL
ANESTHETICS

 Essentially all systemic toxic reactions

associated with local anesthetics are
the result of over-dosage leading to
high blood levels of the agent given.
Therefore, to avoid a systemic toxic
reaction to a local anesthetic, the
smallest amount of the most dilute
solution that effectively blocks pain
should be administered.
 Hypersensitivity. Some patients are
hypersensitive (allergic) to some local
anesthetics. Although such allergies are
very rare, a careful patient history should
be taken in an attempt to identify the
presence of an allergy. There are two
basic types of local anesthetics (the amide
type and the ester type). A patient who is
allergic to one type may or may not be
allergic to the other type.
 CentralNervous System
Toxicities.
Local anesthetics, if absorbed
systematically in excessive amounts,
can cause central nervous system
(CNS) excitement or, if absorbed in
even higher amounts, can cause CNS
depression.
 CNS toxicity cont
 Excitement. Tremors, shivering, and
convulsions characterize the CNS
excitement.
 Depression. The CNS depression is
characterized by respiratory
depression and, if enough drug is
absorbed, respiratory arrest.
 Cardiovascular Toxicities. Local
anesthetics if absorbed systematically in
excessive amounts can cause depression of
the cardiovascular system.
 Peripheral vascular action arteriolar dilation
(except cocaine which is vasoconstrictive
 Hypotension and a certain type of abnormal
heartbeat (atrioventricular block)
characterize such depression. These may
ultimately result in both cardiac and
respiratory arrest.
 Signs of toxicity occur on a continuum.
From early to late stages of toxicity,
these signs are: circum-oral and tongue
numbness, lightheadedness, tinnitus,
visual disturbances, muscular twitching,
convulsions, unconsciousness, coma,
respiratory arrest, then cardiovascular
collapse.
 Types of Local Anesthesia
 Local Infiltration (Local
Anesthesia). Local infiltration occurs
when the nerve endings in the skin
and subcutaneous tissues are blocked
by direct contact with a local
anesthetic, which is injected into the
tissue. Local infiltration is used
primarily for surgical procedures
involving a small area of tissue (for
example, suturing a cut).
 Topical Block. A topical block is
accomplished by applying the anesthetic
agent to mucous membrane surfaces and in
that way blocking the nerve terminals in the
mucosa. This technique is often used during
examination procedures involving the
respiratory tract. The anesthetic agent is
rapidly absorbed into the bloodstream. For
topical application (that is, to the skin), the
local anesthetic is always used without
epinephrine. The topical block easily
anesthetizes the surface of the cornea (of
the eye) and the oral mucosa.
 Surface Anesthesia. This type of
anesthesia is accomplished by the
application of a local anesthetic to
skin or mucous membranes. Surface
anesthesia is used to relieve itching,
burning, and surface pain (for
example, as seen in minor sunburns).
 Nerve Block. In this type of
anesthesia, a local anesthetic is
injected around a nerve that leads to
the operative site. Usually more
concentrated forms of local
anesthetic solutions are used for this
type of anesthesia.
 Peridural Anesthesia. This type of
anesthesia is accomplished by
injecting a local anesthetic into the
peridural space.
 The peridural space is one of the
coverings of the spinal cord.
 Spinal Anesthesia. In spinal
anesthesia, the local anesthetic is
injected into the subarachnoid space
of the spinal cord
 Vasoconstrictors
 Vasoconstrictors decrease the rate of
vascular absorption which allows more
anesthetic to reach the nerve membrane
and improves the depth of anesthesia.
 There is variable response between LA and
the location of injection as to whether
vasoconstrictors increase duration of
action. 1:200,000 epinephrine appears to
be the best vasoconstrictor.