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Local Anaesthetics

I
Dr.U.P.Rathnakar
MD.DIH.PGDHM
www.scribd.com
LA-Definition
Local anaesthetics (LA) are drugs
Which when applied topically or
injected locally,
Block nerve conduction
Cause reversible loss of all sensations
in the restricted part supplied by the
nerve,
Without loss of consciousness
Differences between GA & LA???
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Chem structure-LAs

Cocaine, Procaine,
Chloroprocaine,
Tetracaine, Benzocaine
Lignocaine. Bupivacaine,
Dibucaine, Prilocaine,
Ropivacaine

Intense, Longer lasting
Not hydrolyzed by plasma
esterase
Less hypersensitivity
No cross sensitivity with
ester LAs
Ester linked Amide linked
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Clinical classification of LAs
Injectable anesthetics Surface anesthetics
Short acting with low
potency:
Procaine, Chloroprocaine.
Intermediate acting
with intermediate
potency: Lignocaine,
Mepivacaine, prilocaine
Long acting with high
potency: Tetracaine,
Bupivacaine, Ropivacaine
Soluble:
Cocaine, Lignocaine,
Tetracaine, Benzoxinate
Insoluble
Benzocaine, Oxythazine

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MOA
LA-Injected into interstitial space
Crosses perineurium
Enters endoneural space
Penetrates axonal membrane
Enters axonal space
Binds to receptors in intracellular
half of Na channels
Stabilizes the channel in inactive
state
Reduces the probability of channel
opening
No depolarizationNo threshold potential No AP Conduction block
Disposition of LA in peripheral nerves
Unionized
Ionized
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LA and Sodium channels
LAs bind to receptors -intracellular end of the sodium
channel-active state has higher affinity/more accessible
Threshold for excitation increases,
Finally, the ability to generate an AP is completely
abolished.
If the sodium current is blocked over a critical length of
the nerve, propagation across the blocked area is no longer
possible.
In myelinated nerves, the critical length is two to three
nodes of Ranvier
20
Factors affecting LA action


Size of nerve fibers
Lipophilicity & ph
Concentration of the drug
Proximity to nerve
Location of fibers
Inflammation
Vasoconstrictors
19
Factors affecting LA action
Autonomic, Pain,
temperature,
touch, deep
pressure, motor
function
Bitter-sweet-sour-salt

Diameter of fibers
Small fibers have
closely packed nodes
of Ranvier [more
sensitive-why?
[363KDT]

Motor & sensory nerves are
equally sensitive
[Bupivacaine-blocks sensory
nerves at lower concn.]
Size
Differential sensitivity of nerve fibre
Why?
18
Factors affecting LA action
Lipophilicity & pH
Lipophilic drugs
penetrate the
neuronal
membranes
better.
Unionized forms
penetrate
better
Also increases
tissue binding
and capillary
drainage
Ionized forms
bind to
receptor
17
Concentration of LA
High concn. Provides
favorable
concentration
gradient for
penetration



Nearer the faster
Also favors fast
absorption into
circulation and
toxicity!




Not into the nerve!
Factors affecting LA action
Proximity of application to nerve
16


Factors affecting LA action
of nerve fiber


Location
Fibers in outer layer blocked first
[Proximal areas-represented outside]
Inflammation
Lower pH
Increased blood flow
Adrenaline effect is less
Products of inflammation oppose LA action

15
Vasoconstrictors[1:50000-200000]
Increase contact
period of LAs with
nerve
Counteracts local
vasodilation by
LA[Action on
Symp.fibers]
By decreasing
absorption localizes
the LA
Creates ischemia in
field-less bleeding
Systemic toxicity
Irreversible
hypoxic damage,
tissue necrosis and
gangrene-
Adrenaline CI in
some sites.
Other vasoconstrictors???
Factors affecting LA action
14
Factors affecting.
Size of nerve fibers
Lipophilicity & ph
Concentration of the drug
Proximity to nerve
Location of fibres
Inflammation
Vasoconstrictors
13
Systemic actions
CNS
Stimulation Depression
Inhibition of inhibitory neurons
Inhibition of all neurons.
Cocaine powerful CNS stimulant[euphoria]

Lignocaine numbness, drowsiness
Excitation & convulsions
Convulsion treated by BZDP


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Systemic actions
Heart
CVS toxicity- Inadvertent I.V.
Decreases excitability, conduction rate,
and force of contraction-Hypotension
Lignocaine and procainamide-
Antiarrhythmics
Blood vessels
Symp.blockade Vasodilation
Cocaine Symp. mimetic [Hypertension]
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Systemic actions
Hypersensitivity
Due to-LA or vasoconstrictors
Common with esters.
Preservatives [in Amides or
vasoconstrictors]
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Metabolism

Esters metabolized by plasma esterases
Amides by CYP enzyme
Amides protein bound-Less toxic

PK do not affect efficacy
PK determine toxicity


9
ADEs
CNS-depression followed by excitation
CVS-arrhythmia, hypotension, CV
collapse.
Local toxicity- delays healing, due to
vasoconstrictors?
Hypersensitivity
8
Precautions
Aspirate-to avoid i.v.
Slow injection
Other drugs may lower metabolism of
LAs [Propranolol]
Adrenaline avoided in IHD pts, on
betablockers, TCAs

7
Individual compounds
COCAINE
Abuse liability
Due to inhibition of
catecholamine uptake-DA
Used only For topical use
in Upper Respiratory
Tract
LIGNOCAINE
Faster, Intense, Longer
Eutectic mixture with
Prilocaine-Intact skin

Toxicity.
Drowsiness, tinnitus,
Dysguesia, dizziness, and
twitching. -seizures,
coma, and respiratory
depression and arrest.
Clinical Uses:
Wide range of clinical
uses as a local anesthetic;
Almost any application
where a LA of
intermediate duration is
needed.
Anti-arrhythmic agent
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Individual compounds
PRILOCAINE

EMLA (EUTECTIC MIXTURE
OF LOCAL ANESTHETICS)
Equal quantities of
Lignocaine & Prilocaine.

Topical-5mm depth
By occlusive dressing





Uses-EMLA
IV catheter insertion
Blood sampling,
Superficial surgical
procedures;
Leg ulcers for
cleansing or
debridement
Tattooing
Laser hair removal
Dental-Scaling
Dental-Children
5
Individual compounds
TETRACAINE
Toxic
Topical-Eye, throat,
Tracheo-bronchial

BUPIVACAINE
Long acting
More sensory than motor
Obstetric and post op.pain
reief
Cardiotoxic
ROPIVACAINE
Congener of BUPIVACAINE.
Longer acting
More motor sparing
Less cardio toxic
BENOXINATE
Least irritant
Topically Eye
BENZOCAINE/BUTAMBEN
PABA derivative
Antagonizes Sulfa action
Lozenges-Stomatitis, sore
throat,
Anelgesic powder-ulcers
Suppository-Ano-rectal lesions
4
Local Anaesthetics
II
38
Techniques of LA [Clinical uses]
Topical
Infiltration
Field block
Conduction block
Nerve block
Spinal Epidural Bier block
37
Topical
[EMLA]
Infiltration
Field
[Conduction]
Nerve
[Conduction]
Spinal
Epidural
36
Topical
[EML]
Infiltration
Field
[Conduction]
Nerve
[Conduction]
35
Intact skin not affected [EMLA effective]
Used on mucus membranes
Onset[2-4 mts]-----Lasts [20-40mts]
Adrenaline has no effect
Procedures in-Eye, Nose, Ear, Mouth,
pharynx, Esophagus, Stomach, Intact
skin, Urethra, Anal canal, Rectum

Topical Surface
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Infiltration Anesthesia
Directly injecting LA into tissues to paralyse
sensory nerve endings & small cutaneous
nerves, without taking into consideration the
course of nerves.

Skin and can also include deeper
structures, including intra-abdominal
organs
Duration doubled by adrenaline
Technically simple
Requires more LA for large areas.
33
S.C. injection of L.A. -anesthetize the region
distal to the injection.
Hand, scalp, the anterior abdominal wall,
and the lower extremity
Knowledge of neuroanatomy required
Less quantity ofL.A.
Field block
Conduction block
Nerve block
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Field block
Sup.nerves Fore arm
Ilio inguinal nerve
Nerves of scalp
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Injection of L.A. around individual
peripheral nerves or nerve plexuses
Mixed peripheral nerves - anesthetizes
somatic motor nerves,-skeletal muscle
relaxation

Brachial plexus block-U.Limb & Shoulder
Intercostal block-Ant abd.wall
C.Plexus block-Neck
Sciatic, Ulnar, Median nerve etc.


Field
block
Conduction block
Nerve block
30
Major determinants of anesthesia following
injection near a nerve

1. Proximity of the injection to the nerve
2. Concentration, nature and volume of
drug,
3. Degree of ionization of the drug,
4. Types of nerve fibers
Nerve block Contd
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Biers Block
Esmarch
bandage
28
Biers block-I.V.Regional
Vasculature brings the L.A.to the nerve
trunks and endings
Extremity is exsanguinated with an Esmarch
bandage [Or raise the limb & Block artery]
Proximally located tourniquet is inflated to
100 to 150 mm Hg above SBP
Esmarch bandage is removed,
LA is injected-I.V.
Tourniquet Not less than 30mts-not more
than2 hrs
U.Limb
Lignocaine or Prilocaine with adrenaline
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Dr. August Bier & August Hildebrandt
Needle pricks
Stabbing the thigh
Pulling out pubic hairs
Pulling of chest hair
Smashed a heavy iron hammer
into Hildebrandt's shin bone
Gave his testicles a sharp tug
Rained blows on Hildebrandt's
shin with his knuckles

And none of these hurt a bit!



Spinal anesthesia
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Spinal anesthesia
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Spinal anesthesia
Injected into the subarachnoid
space between Lumbar 2 -3 or
L 3-4
Spinal cord terminates above
the second lumbar vertebra
In this region there is large volume of CSF within
which to inject drug

Minimum direct nerve trauma.

Dose of L.A. produces negligible plasma levels.
Large area is affected


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Pharmacology of Spinal Anesthesia
Commonly used drugs -Lignocaine,
Tetracaine, and Bupivacaine
Factors affecting height and duration-
Volume, speed of injection, baricity ,
position of patient, adrenaline
Adrenaline prolongs duration
Not necessarily due to vasoconstriction
alone
??Decreases nociceptive transmission by
action on
2A
adrenergic receptors in spinal
cord.
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Pharmacology of Spinal Anesthesia-Factors
Baricity [Density]
Decides direction of
migration in the dural
sac
Hyperbaric - settle in
the dependent
portions of the sac,
Hypobaric - Migrate
in the opposite
direction
Isobaric -stay in the
vicinity where they
were injected
Pt.position- till Fixed
Lidocaine and
bupivacaine -isobaric
and hyperbaric
solutions
Diluted with distilled
water -hypobaric
20
Sympathetic blockade
Up to this level
anesthesia
2 segments above-
sympathetic block extends
19
Spinal anesthesia and sympathetic blockade
Differential= pre ganglionic symp
more sensitive
Deleterious and some beneficial
Symp-TL out flow- T1 to LI
Level of blockade is 2 segments
higher than anesthesia
Dominant Para symp action and poor
symp compensation
Not important in children!!
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Spinal anesthesia and sympathetic blockade
Level of spinal block ascends, - CVS
compromise can accelerate
Vasodilation Blood pooling
Venous return becomes gravity-
dependent
CO-Organ perfusion
T1-T4-Card.accelerators
BP=surrogate marker

Treatment
Head down,I.V.Fluids, Ephedrine,
Phenylephrine



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Sympathetic blockade- benefits
Sympathetic fibers -T5 to
L1 inhibit peristalsis
Blockade produces a small,
contracted intestine
Together with a flaccid
abdominal musculature,
produces excellent
operating conditions
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Complications of spinal anesthesia



Prolonged
paralysis

Respiratory
paralysis

Rare
Poor
perfusion
of higher
centers















Hypotension
Symp.Blockade




















Head ache

CSF leak
Small bore
needles




















Cauda equina
syndrome
Damage to
nerve roots




















Septic
meningitis




















Nausea&
Vomiting
Traction of
viscera




















Intercostal
paralysis
Cough[-]











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Contra indications-
Spinal anesthesia
Hypotension & Hypovolemia
[i.v. bolus NS-preop.]
Uncooperative pts
Infants and children-small
segments
Vertebral anomalies
Infection at site of injection





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Spinal anaesthesia
Examples of uses include :-

Lower limb Orthopaedic surgery Total Hip
Replacement
Lower limb Vascular surgery
Hernia (inguinal or epigastric)
Haemorrhoidectomy (Piles), fistulae and
fissures
Abdominal & vaginal hysterectomies
Caesarean sections
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Dermatome levels for different procedures
12
Epidural Anesthesia
Ligamentum
flavum
posteriorly,


Spinal periosteum
laterally,

Dura anteriorly

Site of action-spinal
roots
11
Epidural- categories








Thoracic
Narrow
space
Small vol
of LA
Post OP
pain
relief-
Abd/Tho.
surgeries














Lumbar
Large
volume
Lower
abd,
pelvis,
lower
limbs



Caudal
Sacral canal
Vaginal delivery
Anorectal
operations
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Epidural-
Technically difficult
Large volume
No differential sympathetic
blockade
Blood concentrations of LA much
higher
Area covered depends on volume of
LA
Complications are same as Spinal
Head ache & Neurological
complications are less

9
Epidural uses
An epidural injection or infusion for pain
relief (e.g. in childbirth)
As an adjunct to general anaesthesia. This
may reduce the patient's requirement for
opioid analgesics.
Some operations, most frequently Caesarean
section, may be performed using an epidural
anaesthetic as the sole technique.
For post-operative analgesia,

8
Epidural
The epidural space is more difficult and risky to
access as one ascends the spine (because the spinal
cord gains more nerves as it ascends and fills the
epidural space leaving less room for error),
Epidural techniques are most suitable for analgesia
anywhere in the lower body and as high as the chest.
They are (usually) much less suitable for analgesia
for the neck, or arms
Not possible for the head (since sensory innervation
for the head arises directly from the brain via
cranial nerves rather than from the spinal cord via
the epidural space.)

7
Spinal
Dose-1-4 ml
No indwelling catheter
No systemic absorption
Onset of analgesia 5
minutes
Diff symp block +++


Fixed site-below L2
Easier

Epidural
10-20ml
Indwelling catheter
Systemic absorption +++
Onset of analgesia
15-30 mts
No diff block
[off set by systemic
absorption-2 ]
Varies- Cervical,
thoracic, lumbar
Difficult
6
Epidural
Level=Drug+Volume+Age of pt
Eg:
Ligno+2% of 1-1.5ml+20-
40yrs
=1 segment
5
Epidural- Intrathecal: Opiate Analgesia
Small quantities of opioid injected
intrathecally or epidurally analgesia
Postoperative and chronic pain
Autonomic [BP], sensory[Non-
nociceptive], and motor[Motor
function] nerves is not affected by
the opioids
Morphine, Fentanyl by continuous
infusion
4

Local Anesthetics - Ophthalmological Use

Should be non-irritant
Proparacaine and tetracaine
Instilled a single drop at a
time.
If anesthesia is incomplete,
successive drops are applied
until satisfactory conditions
are obtained.
3
Review-LA
Techniques
Topical, Infiltration, Conduction,
I.V. Regional, Spinal and epidural
Method
Advantages
Complications
Uses
Agents
2
Local Anesthetics Dr.U.P.Rathnakar
www.scribd.com MD.DIH.PGDHM
www.pharmacologyfordummies.blogspot.com
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