LOCAL ANESTHETICS: Local anesthesia is the condition in which sensory transmission

of a local area to CNS is blocked and the chemical agents which cause it are known as
Local anesthetics. Local anesthetics work by blocking sodium channels of excitable
membranes.
Consist of three parts
i.
ii.
iii.

Hydrophilic amino group

Lipophilic aromatic group
Intermediate (ester/amide linkage)

Chemically, esters or amides of simple benzene derivatives (weak bases).

All LA are amphiphilic except benzocaine
Benzocaine, atypical local anesthetic, lack basic group
pKa --- mostly 8-9 (except benzocaine)
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PHARMACOKINETICS:
Short acting- readily absorbed into blood from tissues
Duration is enhanced by co-administration with -agonist to constrict vesselsexcept cocaine
o Cocaine- inhibit nor-epinephrine reuptake into nerve terminals (intrinsic
sympathomimetic activity)
Metabolism of ester LA carried out by plasma cholinesterases (pseudocholinesterases)
o Rapid for procaine
Half life: 1-2min
o Slower for cocaine
o Very slow for tetracaine
Metabolism of amide LA-metabolized in liver, by CYP P450 isoenzymes.
o Half life-Lidocaine, Prilocaine-1.5h
o Half life-Bupivacaine-3.5h
o Half life- Ropivacaine-4.2h
Acidification of urine promotes ionization- Ionized form is more rapidly excreted.
Orally have no effect due to high first pass effect

MECHANISM OF ACTION:
Physiology:
As voltage dependent sodium channels are stimulated by impulse for transmission of
signal, they increase influx of sodium ions causing depolarization of membrane and
allowing the transmission of impulse through nerve.

Pharmacodynamics:

LA block voltage dependent sodium channels so conduction of nerve impulse is

blocked
Drug must be lipid soluble to cross membrane to reach cytoplasm
Once inside axon, drug may be ionized which may more effectively block the
conduction of nerve impulse
pH affect the ionization of drug. At physiologic pH 7.4, drug is ionized.
1. At sites where pH is low like infected tissue, it take more time for action but
higher dose can solve problem
Elevated extracellular potassium ion enhance action of drug
Elevated extracellular calcium ion antagonize action of drug
Blocked by two paths:
1. Hydrophobic pathway via membrane
2. Hydrophilic pathway via inner mouth of channel
Quaternary amine LA work only when applied inside membrane and channel
cycled when open
Tertiary amine LA can work even if closed

Action of LA depend upon

o Fiber diameter
o Myelination
o Physiological firing rate
o Anatomical region
Small fibers are more easily blocked than larger fibers
Myelinated fibers are easily blocked than non myelinated fibers

 Activated pain fibers fire rapidly

Fibers located in periphery of thick nerve bundle are blocked easily than those in
core one because exposure of high concentration of drug

TOXICITY OF LOCAL ANESTHETICS:

CNS
o
o
o
o
o

Sedation
Restlessness
Nystagmus
Tonic clonic convulsion
Severe convulsion followed by coma with respiratory and cardiovascular
depression

Cardiovascular effects
o Vasodilation
o Patient with heart problems may develop heart block and cardiac electrical
function disturbance at high plasma level of drug
o Ropivacaine cardio toxic (less than Bupivacaine) in case of peripheral
nerve block
o Cocaine (nor epinephrine reuptake inhibitor) at sympathetic neurojuntions
and drug vasoconstrictor action may increase cardiovascular toxicity, may
cause tachycardia
In case of drug abuse
Severe hypertension
Cerebral hemorrhage
Arrhythmias
Myocardial infarction
o Breakdown product of esters LA cause allergy so amides are used
Allergic component is Para Amino benzoic acid (PABA), breakdown
product of ester LA
o Liver dysfunction can cause toxicity and increase elimination time in case of
amides LA
o High concentration-local neurotoxic -cause permanent loss of function and
histological damage

TREATMENT OF TOXICITY:

Severe toxicity- treated symptomatically-no antidotes

Convulsions-IV diazepam or short acting barbiturate like thiopental
Hyperventilation with oxygen
Violent convulsive activity- neuromuscular blocker
Bupivacaine cardiovascular toxicity overdose-difficult to treat

PRILOCAINE:
Amide type

Poor vasodilator
Plasma half life- 1.5h
Medium duration of action and onset
Contraindication
o Labor pain because of methemoglobinemia
o Drug-metabolized to o-toluidine which convert hemoglobin to
methemoglobin
Indication
o Symptomatic relief in gastritis
o Obstetric analgesia
Antacid mixture available

TETRACAINE:

Ester type
Derivative of PABA
Long duration
Slow onset
Indication
o Spinal anesthesia
o Surface anesthesia for eye (corneal anesthesia), nose, upper respiratory
tract

BUPIVACAINE:
Produce more sensory blockade than motor blockade
Plasma half life-3.5h
Long duration
Slow onset
Adverse Effect
o Cardiovascular toxicity
o Hypotension
o Arrhythmia
o S isomer is toxic but R is less
Contraindication
o Severe ventricular arrhythmia because of cardio toxicity

TECHNIQUES OF LOCAL ANESTHESIA:

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Surface/Topical anesthesia:
Applied on mucous membrane of nose, mouth, eyes, throat, upper respiratory
tract, esophagus, urethra, ulcers, burns, fissures
Drugs used
o Tetracaine 2%
o Lignocaine 2-10%
o Lidocaine
o benzocaine
Available dosage forms
o Solution
o Ointment
Indication
o Tonometry in eye
o During endoscopy
High concentration can risk systemic toxicity

Infiltration anesthesia:
Injected directly into tissue to be operated-produce sensory blockade (only for
small area)
Injected into skin subcutaneously or intra abdominal organs
Drugs Used
o Lignocaine 0.5-1%
o Procaine
o Bupivacaine
For prolonged action, mixed with adrenaline in ratio of 1:20000-25000
Indications
o Infiltrations
o Drainage of abscess

o Excision of small swelling like lipoma suturing of cut wound episiotomy

Contraindicated in local infection

Field back anesthesia:

Injected subcutaneously
Anesthetize area distal to infection
Indication for minor procedures of:
o Scalp
o Anterior abdominal wall
o Upper and lower extremities
Smaller doses produces larger area of anesthesia

Nerve block anesthesia:

Injected very close or around peripheral nerves
Produces larger areas of anesthesia than field block
Indicated for
o Surgery
o Dentistry
o Analgesia
Onset is slow
Duration is increased by using vasoconstrictor
Less amount of drug is required

Spinal anesthesia:
Injected into subarachnoid space to anesthetize spinal roots
Injected into space between 2-3 or 3-4 below the lower end of spinal cord
Influenced by
o Amount of drug
o Force of injection
o Specific gravity of drug solution
o Position of patient
Drugs used
o Mainly Lidocaine
o Lignocaine
o Tetracaine
o Bupivacaine
Indicated for
o Surgical procedures below level of umbilicus
o Lower limb
o Cesarean
o Obstetric
o Prostectomy
o Surgery of perineal
o Appendectomy

 May cause bradycardia and hypotension

Epidural anesthesia/Intrathecal:
Drugs used
o Lignocaine
o Bupivacaine
Safer technique than spinal anesthesia
Injected into epidural space
Indication
o obstetric analgesia
o painless child birth
Repeated injections may cause tachyphylaxis
Given with opioid analgesic for more effective analgesia

IV regional anesthesia:
Used to anesthetize upper limb
Drugs used
o Lignocaine
o Prilocaine
Injected into vein of limb whose blood flow is occluded by tourniquet
Indication
o limb surgery

Drug Interactions:
Lignocaine and Propranolol
Propranolol reduce hepatic blood flow-Impair clearance of Lignocaine which may result
in toxicity

Procaine and Sulphonamides

Procaine hydrolyzed to PABA that reduces the effect of sulphonamides