LA reversibly block the impulse conduction.
Transient loss of sensation in area of contact.
Used for performing minor surgeries.
Neither cause unconsciousness nor need proper
maintenance of vital functions during surgery.
Mixed nerve- not only sensory but also motor
impulses are interrupted.
Results in muscular paralysis and loss of
autonomic control as well.
Susceptibility of nerve fibers to LA
Differs on the basis of size & myelination.
Small unmyelinated C&B fibers blocked first.
Pain, temp & touch sensation are blocked
Proprioception disappears in succession.
Small typeA-delta fibers(myelin) are blocked
Heavily myelinated A-α, β & ɣ fibers blocked
Skeletal muscle tone is lost in the end.
Recovery takes place in reverse order.
Mechanism of action
LA molecules consist of an aromatic part
liked by an ester or amide bond to a basic
amine side chain.
LA are weak bases
Remain partly ionized at physiological pH.
Unionized form penetrates the N membrane.
In axon- ionized form of LA is active at
LA block the voltage gated Na+ channels..
Blocking action is favored by repetitive
stimulation- voltage dependence.
Activation gate (AG) on extracellular site.
Inactivation gate (IG) on intracellular site.
These gates are called voltage sensors.
Voltage sensors movement is regulated by
conformational change due to voltage
Effect of pH on LA action
LA action is strongly pH dependent.
Partly ionized & partly unionized at physiolog
Unionized form diffuses through axon.
Inside axon it is ionized to cationic form BH+
LA are less effective in infected tissue due to-
1. Acidic pH
2. ↑Blood supply at inflamed site.
3. Effectiveness of Adr ↓ at inflamed site.
4. Inflammatory products may oppose LA
Prolongation of action by
Drugs that delays absorption of LA in to
circulation will prolong its action & reduce
Adrenaline (1:100,000 to 1: 200,000) in
dentistry (1:50,000 to 1: 100,000) MC used
with LA- doubles the duration of LA action.
Vasoconstrictor shouldn’t be used for N block
of an extremity or end organs e.g. on fingers,
toes, nose & penis.
One ampoule of 1:1000 adrenaline in 1 ml volume.
This equals 1mg in 1 ml
This equals 1000 μg/ml
If one ampoule is diluted to 10ml
This equals 0.1 mg/ml
This equals 100 μg/ml
This is 1:10,000 adrenalin
If one ampoule is diluted to 100ml
This equals 0.01 mg/ml
This equals 10 μg/ml
This is 1:100,000 adrenalin
Adr can cause cardiac complications.
Felypressin can be used as an
Preferable in pts with cardiovascular
Alternatively prilocaine can be used.
Stimulation followed by depression.
Symptoms of overdose with clinically used LAs
Abnormal sensation in the tongue,
Dizziness, blurred vision, tinnitus followed by
Drowsiness, dysphoria and lethargy.
Still higher doses produce excitation,
restlessness, agitation, muscle twitching,
seizures and finally unconsciousness.
No significant effects at conventional doses.
High doses- LAs are cardiac depressants.
Decrease automaticity, excitability,
contractility, conductivity and prolong ERP.
Quinidine like antiarrhythmic action.
Procainamide is a class IA antiarrhythmic.
QTc interval is prolonged and LAs can induce
Bupivacaine is relatively more cardiotoxic
Lidocaine used as an antiarrhythmic.
↓ BP due to sympathetic blockade
High conc locally- direct relaxation of arterial
Bupivacaine> Lidocaine> prilocaine
Toxic doses of LAs- cardiovascular collapse.
Cocaine has sympathomimetic property;
↑sympathetic tone, causes local
vasoconstriction, marked rise in BP and
Ester/amide bond in LA governs its
metabolism & ability to cause hypersensitivity
Ester LA are hydrolysed by plasma esterases
& liver esterases.
Spinal fluids contain negligible esterases.
Amide LA are degraded by hepatic
microsomes by N-dealkylation & hydrolysis.
Hypersensitivity more common with ester Las.
First pass metabolism is significant for both
procaine & lidocaine, not used orally in
Cardiac arrhythmias and
Orthotoludine – metabolite of prilocaine.
Oxidises Hb to metHb, ↑levels cause
Rx- reducing agents like methylene blue or
ascorbic acid I.V to convert metHb to Hb.
Ester LA are metabolized to PABA derivatives
Responsible for allergic reactions.
4. Contact sensitization,
5. Asthma and
6. Rarely anaphylaxis occur.
Methylparaben added as preservative in
certain LA solutions is responsible for allergic
Precautions and interactions
Pts on propranolol are very sensitive to
pressor responses of Adr- unopposed 1
Drugs with 1blocking property may lead to
hypotension if co-administered with L+A.
Pts on acute alcohol intoxication need higher
doses of X+A.
In pts on digoxin- accidental I.V inj of Adr
Propranolol can lead to xylocaine toxicity due
1. Inhibition of metabolic oxidation of xylocaine.
Bupivacaine & Levo-Bupivacaine (4>lignocaine)
Uses: nerve block, epidural & spinal anesthesia
More sensory than motor block.
Least placental transmission- painless delivery.
Intermediate onset of action.
Shouldn’t be used for IV regional analgesia or
obstetrical paracervical block anesthesia.
Cardiotoxic- prolongs QTc interval- VT & VA.
Blocks Na channels both in systole &
Aggrevated by acidosis & hypoxemia.
Levo-bupivacaine equally potent but less
Ropivacaine (equipotent to bupivacaine)
Uses: infiltration, epidural & regional
Continous epidural used for relief of post op
& labor pain.
Less cardiotoxic & more motor sparing than
Intermediate onset of action.
Available as S-sterioisomer-
Less affinity for cardiac Na+ channels.
R-isomer is toxic.
Very potent, longest acting LA.
Slow onset of action.
Use: surface anesthetic in anal canal & rectum.
Ocasionally for SA of longer duration. Rarely
More toxic than bupivacaine
Used for dibucaine number test.
Normal dibucaine number is 80.
Lidocaine (Lignocaine) or Xylocaine
Most widely used multipurpose LA
Topically on mucous membrane- Aq.sol, jelly
Infiltration, nerve block & epidural anesthesia.
Spinal analgesia- high conc 5% made
hyperbaric with 7.5% dextrose is used.
Rapid onset of action, lasts for 1-2 hrs.
Opiods are synergistic for intrathecal &
Transdermal patch- for post herpetic
CNS: dizziness, paresthesia & euphoria.
High doses- confusion, vertigo, tinnitus &
Severe toxicity ppt seizures.
Overdose- arrhythmias, ↓BP, coma, resp
Propranolol enhances toxicity by ↓
Ventricular arrhythmias during MI.
Mepivacaine (50% potent as lignocaine)
Similar to lidocaine
Not effective as topical anesthetic.
Can be used without epinephrine.
Articaine (almost equipotent to lidocaine)
Rapid onset of action (5min)
Recently approved for dental & periodontal
procedures. Contains epinephrine.
Also used for spinal & epidural anesthesia
Mainly metabolized by liver, partly by plasma
Prilocaine (equipotent to lidocaine)
Uses: mostly for dental procedures.
Administered by infiltration or nerve block.
Can be used without epinephrine.
Similar to lidocaine
CI in obstetric practice.
Anaesthetise intact skin after surface
Eutectic mixture refers to lowering of melting
point of two solids when they are mixed.
Lidocaine and prilocaine are mixed in equal
proportion at 25°C.
The resulting oil is emulsified into water to
form a cream
Applied under occlusive dressing for 1 hr
1. I.V. cannulation,
2. Split skin graft harvesting and
3. Other superficial procedures.
Anaesthesia up to a depth of 5 mm lasts for
1–2 hr after removal.
It has been used as an alternative to
PRILOX 5% cream.
Tetracaine or Amethocaine (4> lignocaine)
Uses: topically on eye, nose, troat &
Eye: no effect on pupil, accomdation & IOP.
Very suitable for SA of long duration.
Onset of action is slow.
Being PABA ester may antaonise-
I.V doses may produce arrhythmias.
Cocaine (50% potent as lidocaine)
Earlier it was used as ocular anesthetic.
Vasoconstrictor, Adr not necessary.
Protoplasmic poison, causes necrosis on
CNS stimulant- euphoria, delays fatigue,
strong psychological dependence
Bradycardia, ↑BP, ↑temp
Nausea & vomiting
Procaine (25% potent as lidocaine)
No longer used
Slow onset of action, Ineffective topically
Bradycardia, vasodilation, ↓CO.
Anxiety, restlessness & shivering.
Hydrolysed to PABA
Procaine + Benzylpenicillin= procaine
Procainamide- class IA antiarrhythmic.
Chloroprocaine (slightly > procaine)
Better & safer than procaine.
Use: infiltration, nerve block, caudal &
Rapid onset of action.
Not effective topically.
Less toxic than procaine.
Benzocaine & Proparacaine
Used as topical (surface) anesthetics.
Included in preparations of ointment, lozenges
& suppositories- ulcer, sore throat &
Proparacaine preferred in minor ocular
procedures. Non irritant & less antigenic.
PABA derivatives- antagonize sulfonamides.
Too toxic for injection
Uses and techniques of LA
Applied topically on mucous membranes and
Superficial layer is anaesthetised and motor
function not affected.
Onset and duration -site, the drug, conc and
Lidocaine (10%) sprayed in the throat acts in
2–5 min and produces anaesthesia for 30–45
Adr no affect on duration of topical
Phenylephrine can cause mucosal
Absorption of soluble LAs from mucous
membranes is rapid, may attain IV conc.
Eutectic lidocaine/prilocaine is capable of
anaesthetizing intact skin.
Dilute sol of LA is injected under the skin to
reach sensory nerve terminals.
Uses; minor surgical procedures like incisions
Onset of action is almost immediate.
Duration:lidoc 30-60 min, bupiva 90-180 min.
Motor function is not affected.
Conduction block anesthesia
LA injected around the nerve trunk.
Area distal to injection site is anesthetized &
Lidocaine (1–2%) with intermediate duration
of action is most commonly used,
Longer lasting anaesthesia bupivacaine may
LA is injected SC in a manner that all nerves
coming to a particular field are blocked.
Uses: 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.
LA injected around the appropriate nerve
trunks or plexuses.
Latency of anaesthesia depends on the
drug and the area to be covered.
Frequently performed nerve blocks are—
lingual, intercostal, ulnar, sciatic, femoral,
brachial plexus, trigeminal, facial, phrenic,
Used for tooth extraction, operations on
eye, limbs, abdominal wall, fracture setting,
trauma to ribs, neuralgias, persistent
LA is injected in the subarachnoid space
between L2–3 or L3–4.
Nerve roots in the cauda equina are targeted.
Adr may be enhancing spinal anaesthesia by
reducing spinal cord blood flow or
By its own analgesic effect exerted through
spinal α2 adrenoceptors.
Intrathecal clonidine, an α2 agonist, produces
spinal analgesia by itself.
Spinal anaesthesia is used for operations on
the-lower limbs, pelvis, lower abdomen, e.g.
Fracture setting, obstetric procedures,
caesarean section, etc
Advantages of spinal anaesthesia over GA
(i) It is safer.
(ii) Produces good analgesia and muscle
without loss of consciousness.
(iii) Cardiac, pulmonary, renal disease and
diabetes pose less problem
Complications of spinal anaesthesia
Due to Hypotension and ischaemia of
due to blockade of sympathetic outflow to
blood vessels & venous pooling.
Raising the foot end overcomes the
Prevented by ephedrine, mephentermine.
Cauda equina syndrome
Prolonged loss of control over bladder and
It may be due to traumatic damage to nerve
roots or chronic arachnoiditis caused by
inadvertent introduction of the antiseptic or
particulate matter in the subarachnoid space.
Nausea and vomiting
Due to reflexes triggered by traction on
Premedication with opioid analgesics prevents
LA injected in dural space, acts on nerve
Injection is made in the midthoracic region.
Epidural space in this region is relatively
Analgesia obtained in middle and lower
epidural space is wide.
Produces anaesthesia of lower abdomen,
pelvis and hind limbs.
Use is similar to that of spinal anaesthesia.
Injection is given in the sacral canal through
the sacral hiatus.
Produces anaesthesia of pelvic and perineal
Used mostly for vaginal delivery, anorectal and
Cardiovascular complications are similar to
Headache & neurological complications are