This document provides information on local anesthetics (LAs), including their classification, mechanism of action, effects, and uses. LAs work by blocking sodium channels in nerve cell membranes, preventing the generation and conduction of nerve impulses. They can produce local anesthesia through surface application or injection near sensory nerves or nerve trunks. Common LAs discussed are lidocaine, bupivacaine, and cocaine. Lidocaine is the most widely used due to its versatility, while bupivacaine provides longer-lasting anesthesia. Proper administration of LAs allows for anesthesia of specific body areas and structures.

1. Somesh Chandra
Asst Professor
OSCOP

2. Content
⚫Introduction
⚫Classification
⚫Mechanism of Action
⚫Local Actions
⚫SystemicActions
⚫Pharmacokinetics
⚫Adverse Effects
⚫Cocaine
⚫Lidocaine
⚫Uses and Techniquesof Local Anaesthesia

3. Introduction
⚫Local anaesthetics (LAs) - upon topical application or
local injectioncause reversible lossof sensory perception,
especiallyof pain, in a restricted area of the body.
⚫They block generation and conductionof nerve impulse
at any part of the neurone with which they come in
contact, withoutcausing any structural damage.
⚫Motor impulsesare interrupted when a LA is applied toa
mixed nerve, resulting in muscular paralysis and loss of
autonomiccontrol as well.

4. Differences between General and
Local Anaesthesia

5. Some other drugs, e.g. propranolol, chlorpromazine, H1 antihistaminics, quinine have significant LA
activity, but are not used for this purpose because of local irritancy or other prominent systemic
activity. Local anaesthesia can be produced by cooling as well, e.g. application of ice, CO2 snow,
ethylchloride spray.
Classification

6. Mechanism of Action
⚫The LAs block nerveconduction bydecreasing theentry of
Na+ ions during upstrokeof action potential (AP).
⚫As theconcentrationof the LA is increased, the rateof rise
of AP and maximum depolarization decreases causing
slowing of conduction.
⚫Finally, local depolarization fails to reach the threshold
potential and conduction block ensues.
⚫The LAs interactwith a receptorsituated within thevoltage
sensitive Na+ channel and raise the threshold of channel
opening: Na+ permeability fails to increase in response to
an impulseorstimulus.

7. Mechanism of Action
Model of the axonal Na+ channel depicting the site and mechanism of action of
local anaesthetics.
•The Na+ channel hasan activation gate (make or ‘m’ gate) near its extracellular
mouth and an inactivation gate ( haltor ‘h’ gate) at the intracellular mouth.
•In the resting statetheactivation gate isclosed.
•Threshold depolarization of the membraneopens theactivation gateallowing
Na+ ions to flow in along theconcentration gradient.
•Within a few msec, the inactivation gateclosesand ion flow ceases.
•Thechannel recovers to the resting state in a time-dependent manner.

8. ⚫The local anaesthetic (LA) receptor is located within the
channel in its intracellular half.
⚫The LA traverses the membrane in its unionized lipophilic
form (B), reionizes in the axoplasm and approaches the LA
receptor through the intracellular mouth of thechannel.
⚫It is thecationic form (BH+) of the LA which primarily binds
to the receptor.
⚫The receptor has higheraffinityto the LA in theactivated as
well as inactivated states compared to the resting state.
⚫Binding of LA to its receptorstabilizes thechannel in the
inactivated stateand thus reduces the probabilityof channel
opening.
Mechanism of Action

9. Local Actions
⚫LAs have no/minimal local irritant action and block
sensory nerve endings, nerve trunks, neuromuscular
junction, ganglionic synapse through decreased Na+
permeability.
⚫LAs reduce release of acetylcholine from motor nerve
endings and at mixed nerve they cause anaesthesia of
skin and paralysisof thevoluntary muscle.
⚫The sensitivity to LA is determined by diameter of the
fibres as well as by fibre type.
⚫Fibres that are more susceptible to LA are the first to
be blocked and the last torecover.

10. Systemic Actions
⚫ Any LA injected or applied locally is ultimately absorbed and can
produce systemiceffectsdepending on theconcentrationattained in
the plasmaand tissues.
⚫ C.N.S.
⚫ All LAs arecapableof producing a sequenceof stimulation followed
bydepression.
⚫ Cocaine is a powerful CNS stimulant causing in sequence euphoria—
excitement—mental confusion— restlessness—tremorand twitching
of muscles—convulsions—unconsciousness—respiratory
depression—death, in adose-dependent manner.
⚫ Procaine and other synthetic LAs are much less potent in this regard.
⚫ Higherdose oraccidental i.v. injection produces CNS stimulation
followed bydepression.
⚫ The basic action of all LAs is neuronal inhibition; the apparent
stimulation seen initially is due to inhibition of inhibitory neurones.

11. C.V.S.
⚫LAs are cardiac depressants, but no significanteffectsare
observed at conventional doses.
⚫They havea quinidine likeantiarrhythmicaction.
⚫Amide derivative procainamide is a class IA antiarrhythmic .
⚫Bupivacaine is relatively more cardiotoxic and has produced
ventriculartachycardia or fibrillation.
⚫Lidocaine has little effect on contractility and conductivity
⚫It is used as an antiarrhythmic.
Blood vessels
⚫LAs tend to produce fall in BP.This is primarily due to
sympathetic blockade, but highconcentrations, as obtained
locally at the site of injection, do cause direct relaxation of
arteriolarsmooth muscle.
Systemic Actions

12. Pharmacokinetics
⚫Soluble surface anaesthetics (lidocaine, tetracaine) are
rapidlyabsorbed from mucous membranesand abraded
areas.
⚫Rateof absorption dependson the blood flow to thearea
of applicationor injection.
⚫Theabsorbed LA being lipophilic is widelydistributed;
rapidly enters highly perfused brain, heart, liver, and
kidney, followed by muscleand otherviscera.
⚫Amide LAs are bound to plasmaα1 acid glycoprotein.
⚫Metabolismof lidocaine is hepatic blood-f lowdependent.

13. Adverse Effects
(1)CNS effects are light-headedness, dizziness, auditory and
visual disturbances, mental confusion, disorientation,
shivering, twitchings, involuntary movements, finally
convulsions and respiratoryarrest. Thiscan be prevented and
treated bydiazepam.
(2) Cardiovascular toxicityof LAs is manifested as bradycardia,
hypotension, cardiac arrhythmias and vascularcollapse.
(3)Injection of LAs may be painful, but local tissue toxicityof
LAs is low. Bupivacaine has the highest local tissue irritancy.
(4)Hypersensitivity reactions like rashes, angioedema,
dermatitis, contact sensitization, asthma and rarely
anaphylaxisoccur.

14. Cocaine
⚫It isa natural alkaloid from leaves of Erythroxylon coca.
⚫Cocaine is agood surface anaestheticand is rapidlyabsorbed
from buccal mucous membrane.
⚫Cocaine produces prominent CNS stimulationwith marked
effecton mood and behaviour.
⚫It induces a sense of wellbeing, delays fatigueand increases
powerof endurance
⚫Cocainealso stimulatesvagal centre→bradycardia; vasomotor
centre→rise in BP; vomiting centre→nausea and vomiting;
temperature regulating centre→pyrexia
⚫In the periphery, it blocks uptakeof NA and Adr into
adrenergic nerveendings.
⚫Theonly indication forcocaine is in ocularanaesthesia.

15. Lidocaine
⚫ Introduced in 1948, it is currently the mostwidely used LA.
⚫ It is aversatile LA, good both forsurfaceapplication as well as
injection and is available in avarietyof forms.
⚫ Injected around a nerve it blocks conduction within 3 min, whereas
procaine may take 15 min; also anaesthesia is more intense and
longerlasting.
⚫ Vasodilatationoccurs in the injected area.
⚫ It is used forsurface application, infiltration, nerve block, epidural,
spinal and intravenous regional block anaesthesia.
⚫ Cross sensitivitywith ester LAs is not seen. In contrast toother LAs,
early central effects of lidocaine are depressant, i.e. drowsiness,
mental clouding, dysphoria, altered tasteand tinnitus.
⚫ Overdose causes muscle twitching, convulsions, cardiac
arrhythmias, fall in BP, comaand respiratoryarrest likeother LAs.
⚫ Lidocaine is a popularantiarrhythmic.

16. Bupivacaine
⚫A potent and long-acting amide linked LA: used for
infiltration, nerve block, epidural and spinal anaesthesiaof
long duration.
⚫ It has becomevery popular in obstetrics (mothercan
actively cooperate in vaginal delivery) and for postoperative
pain relief bycontinuous epidural infusion.
⚫It has high lipid solubility; distributes more in tissues than
in blood afterspinal/epidural injection. Therefore, it is less
likely to reach the foetus (when used during labour) to
produce neonatal depression.
⚫Bupivacaine is more prone to prolong QTc interval and
induceventricular tachycardia orcardiac depression.

17. Uses and Techniques of Local Anaesthesia
1. Surface anaesthesia
⚫It is 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.
⚫Absorption of soluble LAs from mucous membranes is rapid;
blood concentrations of lidocaine and tetracaine sprayed in
throat/tracheobronchial tree approach those attained on i.v.
injection—toxicity can occur.

18. 2. Infiltrationanaesthesia
⚫Dilute solution of LA is infiltrated under the skin in
thearea of operation—blockssensory nerveendings.
⚫Onset of action is almost immediate and duration is
shorterthan thatafter nerve block, e.g. Lidocaine 30–
60 min, bupivacaine 90–180 min.
⚫Infiltration is used for minoroperations, e.g. incisions,
excisions, hydrocele, herniorrhaphy, etc.
⚫When thearea to beanaesthetised is small.
⚫Relatively largeramountof LA is required compared to
the area anaesthetized, but motor function is not
affected.

19. 3. Conduction block
⚫ The LA is injected around nerve trunks so that theareadistal to injection is
anaesthetised and paralysed.
(a) 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, scalpstitching, operationson forearmsand legs,
etc.
(b) Nerve block - It is produced by injecting the LA around the appropriate nerve trunksor
plexuses.
⚫ Theareaof resulting anaesthesia is still largercompared to theamount of drug used.
⚫ Muscles supplied by the injected nerve/plexus are paralysed. The latency of
anaesthesiadepends on thedrug and the area to becovered bydiffusion, e.g. lidocaine
anaesthetises intercostal nerves within 3 min, but brachial plexus block may take 15
min.
⚫ 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.

20. 4. Spinal anaesthesia
⚫ The LA is injected in the subarachnoid space between L2–3 or
L3–4 i.e. below the lowerend of spinal cord.
⚫ The primary siteof action is the nerve roots in the cauda equina
ratherthan the spinal cord.
⚫ Lowerabdomen and hind limbsareanaesthetised and paralysed.
⚫ The level of anaesthesia depends on the volume and speed of
injection, specific gravity of drug solution and posture of the
patient.
⚫ Thedrug solution could be hyperbaric (in 10% glucose) or
isobaric with CSF.
⚫ Spinal anaesthesia is used foroperationson the lower limbs,
pelvis, lower abdomen, e.g. Prostatectomy, fracture setting,
obstetric procedures, caesarean section, etc.
⚫ Choice of the LA forspinal anaesthesiaprimarilydependson the
natureand duration of theoperative procedure.

21. 5. Epidural anaesthesia
⚫ Thespinal dural space is filled with semiliquid fat throughwhich nerve roots
travel.
⚫ The LA injected in this space— acts primarilyon nerve roots (in theepidural
as well as subarachnoid spaces towhich itdiffuses).
⚫ Epidural anaesthesiacan bedivided into 3 categoriesdepending on the site
of injection.
(i) Thoracic- Injection is made in the midthoracic region.
⚫ Theepidural space in this region is relatively narrow, smallervolumeof drug
is needed and awidesegmental band of analgesia is produced.
⚫ It is used generally forpain relief following thoracic/upperabdominal
surgery.
(ii) Lumbar- Relatively largevolumeof drug is needed becauseepidural space
is wide.
⚫ Itproducesanaesthesiaof lowerabdomen, pelvisand hind limbs.
(iii) Caudal - Injection is given in the sacral canal through the sacral hiatus—
producesanaesthesiaof pelvicand perineal region.
⚫ It is used mostly forvaginal delivery, anorectal and genitourinaryoperations.

22. ⚫6. Intravenousregional anaesthesia (Intravascular
infiltration anaesthesia)
⚫It consists of injection of LA in avein of a tourniquetoccluded
limb .
⚫The limb is first elevated toensurevenous drainage bygravity
and then tightlywrapped in an elastic bandage for maximal.
⚫It is mainly used forthe upper limband fororthopedic
procedures.
⚫Obstructing the blood supplyof lower limb is moredifficult
and largervolumeof anaesthetic is needed.
⚫Therefore, it is rarely used for lower limb, except the foot.
⚫Bupivacaine should not beemployed becauseof its higher
cardiotoxicity.

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