Local Anaesthetics

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Local Anesthetics

 A local anesthetic is an agent which upon local

application or local injection produces
reversible loss of sensory perception, especially
pain impulses in a restricted area of the body
without loss of patient consciousness.

 Pain → Temperature → Touch → Pressure →

Skeletal muscle power

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 Pharmacology of local anesthetics –
correct choices and looking to the
future
 History
 Molecular mechanisms
 Characteristics of local anesthesia
 New agents and approaches
 Summary
 History of local anesthesia-1
 Cocaine = natural product
 Properties well-known to Incas
 Chewed coca dripped on
trepanning sites
 1500s: Spaniards seize plantations
& pay workers with coca paste
 Mixed with corn starch, chewed
with guano, CaCO3, or ash; first
example of “free basing”
 Monardes brings coca leaves back
to Europe (1580); fail to achieve
instant popularity of tobacco Erythroxylon coca
 History of local anesthesia-1
 Cocaine = natural product
 Properties well-known to Incas
 Chewed coca dripped on
trepanning sites
 1500s: Spaniards seize plantations
& pay workers with coca paste
 Mixed with corn starch, chewed
with guano, CaCO3, or ash; first
example of “free basing”
 Monardes brings coca leaves back
Trepanning knife
to Europe (1580); fail to achieve
instant popularity of tobacco From Renato Sabbatini, PhD
 History of local anesthesia-1
 Cocaine = natural product
 Properties well-known to Incas
 Chewed coca dripped on
trepanning sites
 1500s: Spaniards seize plantations
& pay workers with coca paste
 Mixed with corn starch, chewed
with guano, CaCO3, or ash; first
example of “free basing” Skulls from
trepanned
 Monardes brings coca leaves back patients
to Europe (1580); fail to achieve
instant popularity of tobacco
www.epub.org.br/cm/n02/ historia/trepan6b.gif
 History of local anesthesia-1
 Cocaine = natural product
 Properties well-known to Incas
 Chewed coca dripped on
trepanning sites
 1500s: Spaniards seize plantations
& pay workers with coca paste
 Mixed with corn starch, chewed
with guano, CaCO3, or ash; first Spaniards and Native
Slaves
example of “free basing”
 From:
Monardes brings coca leaves back
cocamuseum.com
to Europe (1580); fail to achieve
instant popularity of tobacco
 History of local anesthesia-1
 Cocaine = natural product
 Properties well-known to Incas
 Chewed coca dripped on
trepanning sites
 1500s: Spaniards seize plantations
& pay workers with coca paste
 Mixed with corn starch, chewed
with guano, CaCO3, or ash; first
example of “free basing”
 Chewing coca
Monardes brings coca leaves back From:
to Europe (1580); fail to achieve cocamuseum.com
instant popularity of tobacco
1885 Advertisement
Difference between LA and GA

Local Anesthetics General Anesthetics

Local Action CNS

Limited part Whole body

No loss of consciousness Loss of consciousness

Vital parameter monitoring

Required
is not required

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Classification according to
Clinical Use
Injectable Anaesthetics Surface Anaesthetics
Low Potency-Short Acting: Soluble:
 Procaine, Chloroprocaine  Cocaine, Lidocaine,
Tetracaine, Benoxinate
Intermediate potency and Insoluble:
duration:  Benzocaine, Oxethazaine,
 Lidocaine (Lignocaine), Butylaminobenzoate
Prilocaine (Butamben)
High potency, long duration:
 Tetracaine (Amethocaine),
Bupivacaine, Ropivacaine,
Dibucaine (Cinchocaine)

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 Chemistry
 Weak bases + Amphiphilic nature

 Formulated as hydrochloride salts to make them water

soluble

 Hydrophilic secondary or tertiary amine on one side and

a lipophilic aromatic residue on the other are joined by
an alkyl chain through an ester or amide linkage

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Classification according to
Structure

 Ester linked LAs: Cocaine, procaine,

Chloroprocaine, Tetracaine, Benzocaine

 Amide linked LAs: Lidocaine, Bupivacaine,

Prilocaine, Dibucaine, Ropivacaine

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Features of Amide LAs

 Produce more intense and longer lasting

anesthesia

 Bind to α1 acid glycoprotein in plasma

 Not hydrolyzed by plasma esterases

 Rarely cause hypersensitivity reactions; no

cross sensitivity with ester LAs
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 Ester LA’s - Short DOA, Less intense analgesia
& Higher risk of hypersensitivity

 Rarely used

 Infiltration anaesthesia or Nerve block

 Common use – Topical application

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Mechanism of Action

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 Nerves

 Small diameter nerves are more easily

blocked than large diameter nerves

 For the same diameter, myelinated nerves

will be blocked before unmyelinated nerves.

 Nerves that fire frequently are preferentially

blocked over nerves that fire infrequently.
Local actions
 LAs have no/minimal local irritant action

 Block structures which function through increased

Na+ permeability (nerve endings, nerve trunks,
neuromuscular junction, ganglionic synapse and
receptors)

 Sensory and motor fibres are equally sensitive

 In general, small nerve fibers are more susceptible

than large fibers 21
 Reduce release of Ach from nerve endings

 Injected around a mixed nerve they cause

anaesthesia of skin and paralysis of the
voluntary muscle supplied by that nerve

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 Blockade:

 Myelinated fibres → Non-myelinated fibres

 Small fibres → Large fibres

 Sensory fibres → Motor fibres

 In the somatic fibers:

 Pain → Cold → Warmth → Touch →

Pressure

 Bitter → Sweet → Sour → Salt

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Factors Affecting Actions of LA
 pKa: (Dissociation Constant)

 Higher pKa more is the ionized fraction, slow

onset of action & vice-versa

 Plasma Protein Binding: ↑PPB - ↑ duration of

action. E.g.: Procaine(↓), & Bupivacaine (↑)

 Rate of diffusion of SOA:

 Lipid solubility: Lignocaine (↑) & Procaine (↓)

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 Effect of pH

 Inflamed tissue: Inflammation lowers pH of

the tissue, increased blood flow

 Effect of vasodilator activity - greater

vasodilator activity – Decreased potency and
decreased duration of action
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Addition of a vasoconstrictor
 E.g.: Adrenaline, Phenylephrine,

 Prolongs duration of action of LAs by decreasing

their rate of removal from the local site into the
circulation

 Enhances the intensity of nerve block

 Reduces systemic toxicity of LAs

 Bloodless field for surgery

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 Disadvantages:

 Injection more painful

 Vasospasm & Ischemia – End arteries

 Increases the chances of subsequent local

tissue edema and necrosis

 May raise BP

 Delayed Wound healing

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Pharmacological Actions

 PNS:

 Pain → Cold → Warmth → Touch →

Pressure

 Bitter → Sweet → Sour → Salt

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 CNS:

 Stimulation → Depression

 Euphoria → Excitement → Confusion →

Restlessness → Tremors → Twitching →
Convulsions → Unconsciousness → Respiratory
depression → Death

 Dose dependent

 Cocaine potent CNS stimulant

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 Rest all safe at CLINICAL DOSE

 Lignocaine – Circumoral numbness → Abnormal

sensation in tongue → Dizziness → Blurred
vision → Tinnitus → Drowsiness → Dysphoria
→ Lethargy → (More higher doses) → Excitation
→ Restlessness → Agitation → Muscle twitching
→ Seizures → Unconsciousness

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 Heart:

 Cardiac depressants

 Large dose / i.v. injection - ↓ Automaticity,

Excitability, Contractility, Conductivity,
Prolong Effective Refractory Period

 Antiarrhythmic action (Procainamide)

 BUT LAs can induce Arrhythmia itself

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 Bupivacaine (Cardiotoxic) – Ventricular
tachycardia / Ventricular fibrillation

 Lignocaine – Abbreviates ERP

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 Blood Vessels:

 Fall in BP (Sympathetic blockade)

 High dose – direct relaxation of Blood vessels

 Bupivacaine > > Lignocaine > Prilocaine

 Cocaine – Sympathomimetic action - ↑ CVS

actions

 Large toxic doses – Collapse of CVS

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Kinetics

 Esters – Plasma esterases

 Amides – Liver
 Procaine, Lignocaine – High 1st pass
metabolism
 Cautious in Liver disorder (Lignocaine)

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 Surface anaesthetics absorbed easily from
abraded skin than intact
 Procaine – NO penetration through mucous
membrane
 Lipophilic LAs widely distributed – Enters
easily → Brain, Heart → Liver → Kidney →
Muscle
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ADR
 Central Nervous System

 Light headedness, dizziness, visual and

auditory disturbances, Excitement,
confusion, Tremors, shivering, and
convulsions followed by respiratory
depression.

 Cardiovascular System.

 Bradycardia, Hypotension, cardiac

arrhythmia (Bupivacaine)
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 Local

 Circumoral and tongue numbness,

delay in wound healing and ring block
(along with adrenaline)

 Hypersensitivity (allergic) reactions

(esters)

 Methemoglobinemia by Prilocaine

 Neurotoxicity by Chloroprocaine

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Precautions and interactions
 Before injecting the LA, aspirate lightly to
avoid intravascular injection

 Inject the LA slowly and take care not to

exceed the maximum safe dose

 Vasoconstrictor containing LA should be

avoided for patients with IHD, uncontrolled
hypertension, cardiac arrhythmia and areas
of end arterial circulation
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USES & TECHNIQUES OF LOCAL
ANESTHESIA

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 SURFACE ANESTHESIA

 It is produced by topical application of a surface

anesthetics to mucous membrane and abraded
skin.

 Painful lesions of oral cavity, tonometry,

endoscopy, endotracheal intubation, gastritis,
ulcers, burns, Proctoscopy, catheterization, piles

 E.g.: Lignocaine (2-10%), Tetracaine (2%),

Benzocaine
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Infiltration anesthesia

 Dilute solution of LA is infiltrated under the skin in

the area of operation – blocks sensory nerve
endings.

 Infiltration is used for minor operations, like -

incisions, excisions, etc.

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 Conduction block

The LA is injected around nerve trunks so

that area distal to injection is
anesthetized and paralyzed.
a. Field block: All nerves coming to a
particular field are blocked. Used in
appendicectomy, dental procedures,
scalp stitching.
b. Nerve block: LA around the
appropriate nerve trunks or
plexuses. Frequently performed
nerve blocks are – lingual,
intercostal, ulnar, brachial plexus etc.
Used for tooth extraction, operations
on eye, limbs, abdominal wall,
fracture setting etc
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 Spinal anesthesia

 The LA is injected in the sub arachnoid space between L2-3 or L3-4

i.e below the lower end of spinal cord.
 The primary site of action is the nerve root in the cauda equina rather
than the spinal cord.
 Level of anesthesia depends on volume, speed, sp.gravity and posture
 Hyperbaric or isobaric

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 Spinal anesthesia is used for operations on the
lower limbs, pelvis, lower abdomen,
prostectomy, fracture setting etc.
 Advantages over GA are:
 Safe
 Produces good analgesia and muscle relaxation
without loss of consciousness
 Cardiac, pulmonary, renal disease and diabetes
pose less problem
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Complications of spinal anaesthesia

Respiratory paralysis- intercostals muscles

may paralyzed

Hypotension-due to blockade of sympathetic

outflow to blood vessels

Cauda equina syndrome-due to prolonged loss

of control over bladder & bowel sphincter

Headache, septic meningitis, nausea & vomiting

Contraindications to spinal anesthesia

 Hypotension and hypovolemia

 Uncooperative or mentally ill patients
 Infants and children – control of level is difficult
 Vertebral abnormalities
 Sepsis at injection site

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Epidural anaesthesia
Method
Injection in spinal epidural space where
Nerve roots travel

Divided into 3 categories-

• Thoracic -used for pain relief in thoracic/upper
abdominal surgery
• Lumbar- operation of lower limbs, pelvis & lower
abdomen
• Caudal-injection is given in sacral canal; used for
vaginal delivery & genitourinary operations
Epidural spinal

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ravenous regional anaesthesia
Method
• LAs injected in vein of tourniquet
occluded limb
• Drug diffuses retrograde from peripheral
vascular bed to non vascular tissues
including nerve endings

• Application
Used for upper limb & orthopedic procedures
• Prilocaine, lidocaine
Newer Techniques of LA

Iontophoresis:
Repulsive electromotive force propels
high Conc. of drug transdermaly

Iontocaine:
 2% lidocaine + 0.01mg/ml epinephrine sol.
 Administered via iontophores through Skin
 Numb up to 10 mm of skin in 2 min.
Newer Techniques of LA

Liposomes: Liposomal Bupivacaine Formulation

 Liposomes: artificially prepared vesicle

made up of lipid bilayer, can be filled
drug & used to deliver

 Liposome bupivacaine formulation-

form by loading buoivacaine along
Ammonium sulfate gradient
LAs-Therapeutic uses

Acute Chronic
Pain Pain

Surgery Dentistry
 Cont

• Conduction block anaesthesia preferred because

– superior pain control & fewer side effects
Acute • given by repeated inj/continuous infusion
Pain • Labour pain - epidural anaesthesia
• Post operative pain - nerve block
• Tramua - intravenous regional anaesthesia

• Applied repeatedly/ continuously for prolonged

Chronic period
Pain • LA used in combination with opioids, NSAIDs &
anticonvulsants
 Cont
• Eye surgery – topical anaesthesia for retro
bulbar block
• Head & neck surgery – infiltration
Surgery anaesthesia & field block
• Shoulder & arm surgery – plexus anesthesia
• Gynecological & Urological operations –
spinal/epidural anaesthesia

• Restorative operation/Extractions –
Dentistry
infiltration & regional nerve block anaesthesia
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THE END

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