LOCAL

ANAESTHETICS

PREPARED BY MRS. K. GLADYS KALPANA

 INTRODUCTION
• Local anaesthetics are drugs which, when applied
directly to peripheral nerves, block nerve conduction
and abolish all sensations in the part supplied by the
nerve.
• They are applied to somatic nerves and act on axons,
cell body, dendrites and synapses.
• Local anaesthesia can also be produced by physical
methods such as refrigeration, application of ice and
ethyl chloride spray.
 GENERAL PROPERTIES OF LOCAL
ANAESTHETICS
• LAs are water and lipoidal soluble in nature; since the
nervous tissue is rich in lipid, lipoidal solubility helps
the drug to move into the neuronal fibre, while water
solubility helps to get the drug to the site of action
from the site of injection or application.
• Thus, the LA with high lipid but low water solubility
will not be much useful because of difficulty in
transportation through the aqueous phase
surrounding the neuronal fibre.
• Chemically, the useful local
anaesthetics consist of three parts
• (1) A hydrophilic amino group.
• (2) An intermediate chain; and
• (3) A lipophilic aromatic group.
• Their generic name ends with
the suffix ‘caine’.
Non-nitrogenous compounds with local
anaesthetic properties like benzyl
alcohol have their generic names
ending with suffix ‘ol’, e.g.
propanediol, cyclohexanol.
 CLASSIFICATION
• Natural: Cocaine.
• Synthetic nitrogenous compounds:
• Derivatives of para-aminobenzoic acid.
– Freely soluble: Procaine, Amethocaine.
– Poorly soluble: Benzocaine, Orthocaine.
• Derivatives of acetanilide, e.g., Lignocaine (Lidocaine).
• Quinoline derivatives, e.g., Cinchocaine (Nupercaine).
• Acridine derivatives, e.g., Bucricaine
• Synthetic non-nitrogenous compounds:
– Benzyl alcohol, Propanediol.
• Miscellaneous drugs with local action: e.g. Clove oil, Phenol,
Chlorpromazine, antihistaminics like Diphenhydramine.
 MECHANISM OF ACTION
• Reversibly block nerve conduction near the site of administration, there
by producing temporary loss of sensation in a limited area.
• Block both the generation and the conduction of the nerve impulse.
• Bind to receptors near the intracellular end of the voltage gated sodium
channels.
• This prevents the increase in permeability of the cell membrane to Na+
ion, the first event in depolarisation (Sodium Channel Block).
• Thus, an action potential is not generated. This action affecting the
process of depolarisation, leading to failure of impulse propagation
without affecting the resting potential, is known as membrane
stabilising effect.
• Increased extracellular calcium antagonises the action of local
anaesthetics on nerves and muscles, while potassium facilitates the
same.
 MECHANISM OF ACTION
• A smaller nerve fibre presents a greater surface area per unit
volume for the action of an anaesthetic than a larger fibre.
Smaller fibres are, therefore, blocked first.
• Thus, the various fibres are blocked in the following order:
• Autonomic fibres
– Sensory fibres conducting temperature and pain
• Sensory fibres carrying touch, pressure and
vibration sensations; and
• Motor fibres
• Recovery of function occurs in the reverse order.
 PHARMACOLOGICAL ACTION
• Stimulate CNS and cause restlessness, tremors and in toxic
doses, convulsions.
• Myocardiac depressants, decrease heart rate and the
amplitude of contraction.
• Procainamide (related to procaine) and lignocaine are used
therapeutically for their cardiac depressant properties.
• Cocaine is a vasoconstrictor.
• Other actions: Synthetic nitrogenous local anaesthetics have
a direct spasmolytic action on smooth muscle and in large
doses, they can produce neuromuscular blockade.
 PHARMACOKINETICS
• Local anaesthetics are not absorbed from unbroken
skin.
• Applied to the mucous membrane, the absorption
varies with the mucous surface.
• Thus, absorption is more rapid from the trachea than
from the pharynx while it is poor through the urinary
bladder.
• Metabolised liver and plasma.
• Excreted unchanged in human urine.
 ADVERSE REACTIONS
• Mild allergic dermatitis, a typical asthmatic attack or
a severe fatal anaphylactoid reaction.
• Fall of BP and cardiac arrest can occur sometimes.
• Oxygen is given to prevent hypoxia.
• Factors which determine the toxicity are:
• The rate of absorption, diffusion and inactivation of
the drug.
• Individual susceptibility
• Inherent toxicity of the drug
 PREVENTION OF TOXICITY
• Enquire about the history of allergy.
• Drugs should be given cautiously in the presence of liver and
myocardial damage.
• Avoid food at least 4 hours prior to anaesthesia to prevent
vomiting. Pre-anaesthetically diazepam may be given.
• Select the proper site. Correct knowledge of the nerve course
is needed before attempting a nerve block.
• Use minimal effective dose, well diluted.
• Avoid intravenous administration.
• Wait after injection. Remember the latent period.
• Observe post-operatively for allergic reactions.
 COCAINE
• Alkaloid from the leaves of the coca tree (Erythroxylon coca)
and other species.
• It is the methylbenzoyl ester of ecgonine which is chemically
closely related to atropine.
• Cocaine is not used as a local anaesthetic; but it is an
important drug of abuse for its psychotropic effects.
• It acts on peripheral nerves as a membrane stabiliser and
hence as a local anaesthetic.
• It blocks the reuptake of dopamine and causes activation of
the dopaminergic system, leading to sense of euphoria
(mesolimbic and mesocortical pathways), strongly
reinforcing the addicting property of the drug.
• Cocaine produces prominent CNS stimulation with marked effect
on mood and behaviour.
• It induces a sense of wellbeing, delays fatigue and increases power
of endurance.
• In susceptible individuals it produces a state referred to as ‘high’
leadting to strong psychological but little physical dependence.
• Cocaine is unique among drugs of abuse in not producing
significant tolerance on repeated use; sometimes reverse
tolerance is seen (behavioural effects are experienced at lower
doses).
• Cocaine also stimulates vagal centre→bradycardia; vasomotor
centre→rise in BP; vomiting centre→nausea and vomiting;
temperature regulating centre→pyrexia (also due to increased
heat production as a result of enhanced muscular activity).
 LIDOCAINE (LIGNOCAINE)
• Most widely used LA, good both for surface application as well as
injection and is available in a variety of forms.
• Injected around a nerve it blocks conduction within 3 min, whereas
procaine may take 15 min; also anaesthesia is more intense and longer
lasting. Vasodilatation occurs in the injected area.
• It is used for surface application, infiltration, nerve block, epidural,
spinal and intravenous regional block anaesthesia.
• In contrast to other LAs, early central effects of lidocaine are
depressant, i.e. drowsiness, mental clouding, dysphoria, altered taste
and tinnitus.
• Overdose causes muscle twitching, convulsions, cardiac arrhythmias,
fall in BP, coma and respiratory arrest like other LAs.
• Lidocaine is a popular antiarrhythmic
 TETRACAINE (AMETHOCAINE)
• A highly lipid-soluble PABA ester, more potent and
more toxic due to slow hydrolysis by plasma
pseudocholinesterase.
• It is both surface and conduction block anaesthetic, but
its use is restricted to topical application to the eye, nose,
throat, tracheobronchial tree and rarely for spinal or
caudal anaesthesia of long duration.
• Though it is slow acting, absorption from
tracheobronchial spray is very fast and blood
concentrations approach those attained after i.v.
injection.
 BUPIVACAINE
• A potent and long-acting amide-linked LA:
• Used for infiltration, nerve block, epidural and spinal anaesthesia of long
duration.
• 0.25–0.5% solution injected epidurally produces adequate analgesia
without significant motor blockade.
• Used in obstetrics and for postoperative pain relief by continuous epidural
infusion. It has high lipid solubility;
• Distributes more in tissues than in blood after spinal/epidural injection.
• It is less likely to reach the foetus (when used during labour) to produce
neonatal depression.
• More prone to prolong QTc interval and induce ventricular tachycardia or
cardiac depression—should not be used for intravenous regional analgesia.
• Epidural anaesthesia with 0.75% bupivacaine during labour has caused few
fatalities due to cardiac arrest; use of this concentration is contraindicated.
 ROPIVACAINE
• A newer bupivacaine congener, equally long acting but less
cardiotoxic.
• It blocks Aδ and C fibres (involved in pain transmission) more
completely than Aβ fibres which control motor function.
• Though equi-effective concentrations of ropivacaine are higher
than those of bupivacaine, a greater degree of separation between
sensory and motor block has been obtained with epidural
ropivacaine.
• Continuous epidural ropivacaine is being used for relief of
postoperative and labour pain.
• It can also be employed for nerve blocks.
• Recently, it has been approved for use in India.
 THERAPEUTIC USES

• Surface anaesthesia:
• Infiltration anaesthesia:
• Nerve block or conduction block
• Spinal anaesthesia
• Epidural anaesthesia
 SURFACE ANESTHESIA
• Produced by topical application of a surface anaesthetic to mucous
membranes and abraded skin.
• Only the superficial layer is anaesthetised and there is no loss of
motor function.
• Onset and duration depends on the site, the drug, its concentration
and form, e.g. lidocaine (10%) sprayed in the throat acts in 2–5 min
and produces anaesthesia for 30–45 min.
• Addition of Adr does not affect duration of topical anaesthesia, but
phenylephrine can cause mucosal vasoconstriction and prolong
topical anaesthesia.
• Absorption of soluble LAs from mucous membranes is rapid; blood
concentrations of lidocaine and tetracaine.
 INFILTRATION ANAESTHESIA
• Dilute solution of LA is infiltrated under the skin in the area of
operation—blocks sensory nerve endings.
• Onset of action is almost immediate and duration is shorter
than that after nerve block, e.g. lidocaine 30–60 min,
bupivacaine 90–180 min.
• Infiltration is used for minor operations, e.g. incisions,
excisions, hydrocele, herniorrhaphy, etc. when the area to be
anaesthetised is small.
• Relatively larger amount of LA is required compared to the
area anaesthetized, but motor function is not affected.
 CONDUCTION BLOCK
• The LA is injected around nerve trunks so that the area distal to injection
is anaesthetised and paralysed.
• Choice of the LA and its concentration is mainly dictated by the required
duration of action;
• lidocaine (1–2%) with intermediate duration of action is most commonly
used, but for longer lasting anaesthesia bupivacaine may be selected.
• Field block:
• It is produced by injecting the LA subcutaneously in a manner that all
nerves coming to a particular field are blocked—as is done for
herniorrhaphy, appendicectomy, dental procedures, scalp stitching,
operations on forearms and legs, etc.
• Larger area beginning 2–3 cm distal to the line of injection can be
anaesthetised with lesser drug compared to infiltration.
• The same concentration of LA as for infiltration is used for field block.
 CONDUCTION BLOCK
• Nerve block:
• It is produced by injecting the LA around the appropriate nerve trunks or
plexuses.
• The area of resulting anaesthesia is still larger compared to the amount of
drug used.
• Muscles supplied by the injected nerve/plexus are paralysed.
• The latency of anaesthesia depends on the drug and the area to be
covered by diffusion, e.g. lidocaine anaesthetises intercostal nerves
within 3 min, but brachial plexus block may take 15 min. For plexus block
a ‘flooding’ technique is used and larger volumes are needed.
• Nerve block lasts longer than field block or infiltration anaesthesia.
Frequently performed nerve blocks are—lingual, intercostal, ulnar,
sciatic, femoral, brachial plexus, trigeminal, facial, phrenic, etc.—used for
tooth extraction, operations on eye, limbs, abdominal wall, fracture
setting, trauma to ribs, neuralgias, persistent hiccup, etc.
 SPINAL ANAESTHESIA
• LA is injected in the subarachnoid space between L2–3 or L3–4 i.e. below
the lower end of spinal cord.
• The primary site of action is the nerve roots in the cauda equina rather
than the spinal cord. Lower abdomen and hind limbs are anaesthetised
and paralysed.
• The level of anaesthesia depends on the volume and speed of injection,
specific gravity of drug solution and posture of the patient.
• The duration of spinal anaesthesia depends on the drug used and its
concentration.
• Addition of 0.2–0.4 mg of adrenaline to the LA prolongs spinal
anaesthesia by about 1/3rd when measured by the time taken for the level
of sensory block to recede to L1.
• Adr may be enhancing spinal anaesthesia by reducing spinal cord blood
flow or by its own analgesic effect exerted through
 SPINAL ANAESTHESIA
• Women during late pregnancy require less drug for spinal anaesthesia,
because inferior vena cava compression leads to engorgement of the
vertebral system and a decrease in the capacity of subarachnoid space.
• Spinal anaesthesia is used for operations on the lower limbs, pelvis,
lower abdomen, e.g. prostatectomy, fracture setting, obstetric
procedures, caesarean section, etc.
• Choice of the LA for spinal anaesthesia primarily depends on the
nature and duration of the operative procedure.
• Advantages of spinal anaesthesia over general anaesthesia are:
• (i) It is safer.
• (ii) Produces good analgesia and muscle relaxation
• without loss of consciousness.
• (iii) Cardiac, pulmonary, renal disease and
• diabetes pose less problem.
 COMPLICATIONS OF SPINAL ANAESTHESIA
• Respiratory paralysis
• Hypotension
• Headache
• Cauda equina syndrome
• Septic meningitis
• Nausea and vomiting
 EPIDURAL ANAESTHESIA
• The spinal dural space is filled with semiliquid fat through
which nerve roots travel.
• The LA injected in this space—acts primarily on nerve roots (in
the epidural as well as subarachnoid spaces to which it
diffuses) and small amount permeates through intervertebral
foramina to produce multiple paravertebral blocks.
• Epidural anaesthesia can be divided into 3 categories
depending on the site of injection.
– Thoracic
– Lumbar
– Caudal
 INTRAVENOUS REGIONAL ANAESTHESIA
(INTRAVASCULAR
INFILTRATION ANAESTHESIA)

• It consists of injection of LA in a vein of a tourniquet

occluded limb such that the drug diffuses retrograde
from the peripheral vascular bed to nonvascular
tissues including nerve endings.
• It is mainly used for the upper limb and for
orthopaedic procedures.
 FREQUENTLY ASKED QUESTIONS

• Explain Local anaesthetics – adverse reactions.

• Classification and Mechanism of action of Local
Anaesthetics.
• Adverse effects of Local Anesthetics.
• Classify local anaesthetics. Mention the therapeutic
uses of lignocaine.
• Write in detail about local anaesthesia
• Categorize local anaesthetic drugs. Discuss the
mechanism and dose of lignocaine.