references- sharma & sharma K.D Tripati

1. Local Anesthetics
Dr.K.R.Prabhakar
Asst.Professor

2. Introduction
 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.

3. Susceptibility of nerve fibers to LA
blockade
 Differs on the basis of size & myelination.
 Small unmyelinated C&B fibers blocked first.
 Pain, temp & touch sensation are blocked
first.
 Proprioception disappears in succession.
 Small typeA-delta fibers(myelin) are blocked
next.
 Heavily myelinated A-α, β & ɣ fibers blocked
last.
 Skeletal muscle tone is lost in the end.
 Recovery takes place in reverse order.

5. Classification
Amide type
Long acting
 Bupivacaine
 Levo-Bupivacaine
 Ropivacaine
 Dibucaine
Intermediate acting
 Lidocaine
(lignocaine)
 Mepivacaine
 Prilocaine
 Articaine
Ester type
Long acting
 Tetracaine
(amethocaine)
Intermediate acting
 Cocaine
Short acting
 Procaine
 Chloroprocaine
 Benzocaine
 Proparacaine

6. Miscellaneous
 Pramoxine (pramocaine)
 Dyclonine
 Oxethazaine (mucaine)

7. 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
receptor site.

9.  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
gradient.

11. Effect of pH on LA action
 LA action is strongly pH dependent.
 Partly ionized & partly unionized at physiolog
pH.
 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
action.

12. Prolongation of action by
vasoconstrictors
 Drugs that delays absorption of LA in to
circulation will prolong its action & reduce
systemic toxicity.
 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.

13.  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

14.  Adr can cause cardiac complications.
 Felypressin can be used as an
alternative.
 Preferable in pts with cardiovascular
diseases.
 Alternatively prilocaine can be used.

15. Systemic actions
C.N.S
 Stimulation followed by depression.
Symptoms of overdose with clinically used LAs
are-
 Circumoral numbness,
 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.

16. cvs
Heart
 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
cardiac arrhythmias
 Bupivacaine is relatively more cardiotoxic
 Lidocaine used as an antiarrhythmic.

17. Blood vessels
 ↓ BP due to sympathetic blockade
 High conc locally- direct relaxation of arterial
SM.
 Bupivacaine> Lidocaine> prilocaine
 Toxic doses of LAs- cardiovascular collapse.
 Cocaine has sympathomimetic property;
 ↑sympathetic tone, causes local
vasoconstriction, marked rise in BP and

18. Pharmacokinetics
 Ester/amide bond in LA governs its
metabolism & ability to cause hypersensitivity
reactions.
 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
arrhythmias

19. Adverse effects
CNS
Low doses
 Tongue numbness
 Sleepiness
 Mild headache
 Visual & auditory disturbances
High doses
 Nystagmus & muscle twitching.
 Convulsions
 Cocaine- long lasting CNS stimulation &
euphoria.

20. CVS
 Bradycardia,
 Hypotension,
 Cardiac arrhythmias and
 Vascular collapse
Blood
 Orthotoludine – metabolite of prilocaine.
 Oxidises Hb to metHb, ↑levels cause
cyanosis.
 Rx- reducing agents like methylene blue or
ascorbic acid I.V to convert metHb to Hb.

21. Allergic reactions
 Ester LA are metabolized to PABA derivatives
.
 Responsible for allergic reactions.
1. Rashes,
2. Angioedema,
3. Dermatitis,
4. Contact sensitization,
5. Asthma and
6. Rarely anaphylaxis occur.
 Methylparaben added as preservative in
certain LA solutions is responsible for allergic

22. Precautions and interactions
 Pts on propranolol are very sensitive to
pressor responses of Adr- unopposed 1
action.
 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
cause arrhythmias.
 Propranolol can lead to xylocaine toxicity due
to-
1. Inhibition of metabolic oxidation of xylocaine.

23. Amide group
Long duration
Bupivacaine & Levo-Bupivacaine (4>lignocaine)
0.25-0.5%
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.

24. Toxicity
 Cardiotoxic- prolongs QTc interval- VT & VA.
 Blocks Na channels both in systole &
diastole.
 Aggrevated by acidosis & hypoxemia.
 Levo-bupivacaine equally potent but less
toxic.

25. Ropivacaine (equipotent to bupivacaine)
Uses: infiltration, epidural & regional
anesthesia.
 Continous epidural used for relief of post op
& labor pain.
 Less cardiotoxic & more motor sparing than
bupi.
 Intermediate onset of action.
Toxicity
 Available as S-sterioisomer-
 Less affinity for cardiac Na+ channels.
 R-isomer is toxic.

26. Dibucaine (Cinchocaine)
 Very potent, longest acting LA.
 Slow onset of action.
Use: surface anesthetic in anal canal & rectum.
 Ocasionally for SA of longer duration. Rarely
used
Toxicity
 More toxic than bupivacaine
Other uses
 Pseudocholinesterase inhibitor.
 Used for dibucaine number test.
 Normal dibucaine number is 80.

27. Medium duration
Lidocaine (Lignocaine) or Xylocaine
 Most widely used multipurpose LA
Uses:
 Topically on mucous membrane- Aq.sol, jelly
etc.
 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 &
epidural.
 Transdermal patch- for post herpetic

28. Toxicity
 CNS: dizziness, paresthesia & euphoria.
 High doses- confusion, vertigo, tinnitus &
nausea.
 Severe toxicity ppt seizures.
 Overdose- arrhythmias, ↓BP, coma, resp
arrest.
 Propranolol enhances toxicity by ↓
clearance.
Other uses
 Ventricular arrhythmias during MI.

29. 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
cholinesterase.

30. Prilocaine (equipotent to lidocaine)
Uses: mostly for dental procedures.
 Administered by infiltration or nerve block.
 Can be used without epinephrine.
Toxicity
 Similar to lidocaine
 Metabolite orthotoludine
causes metHb.
 CI in obstetric practice.

31. Eutectic lidocaine/prilocaine
 Anaesthetise intact skin after surface
application.
 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

32. Use:
 Applied under occlusive dressing for 1 hr
before
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
lidocaine infiltration.
 PRILOX 5% cream.

33. Ester group
Long duration
Tetracaine or Amethocaine (4> lignocaine)
Uses: topically on eye, nose, troat &
tracheobronchial tree.
 Eye: no effect on pupil, accomdation & IOP.
 Very suitable for SA of long duration.
 Onset of action is slow.
Toxicity:
 Slowly metabolized
 Being PABA ester may antaonise-
sulfonamides.
 I.V doses may produce arrhythmias.

34. Medium duration
Cocaine (50% potent as lidocaine)
 Earlier it was used as ocular anesthetic.
 Vasoconstrictor, Adr not necessary.
 Protoplasmic poison, causes necrosis on
injection.
Toxicity
 CNS stimulant- euphoria, delays fatigue,
strong psychological dependence
 Bradycardia, ↑BP, ↑temp
 Nausea & vomiting

35. Short duration
Procaine (25% potent as lidocaine)
 No longer used
 Slow onset of action, Ineffective topically
Toxicity
 Bradycardia, vasodilation, ↓CO.
 Anxiety, restlessness & shivering.
 Hydrolysed to PABA
Other uses
 Procaine + Benzylpenicillin= procaine
penicillin
 Procainamide- class IA antiarrhythmic.

36. Chloroprocaine (slightly > procaine)
 Better & safer than procaine.
 Use: infiltration, nerve block, caudal &
epidural block.
 Rapid onset of action.
 Not effective topically.
 Less toxic than procaine.

37. Benzocaine & Proparacaine
 Used as topical (surface) anesthetics.
 Included in preparations of ointment, lozenges
& suppositories- ulcer, sore throat &
inflammation.
 Proparacaine preferred in minor ocular
procedures. Non irritant & less antigenic.
Toxicity
 PABA derivatives- antagonize sulfonamides.
 Too toxic for injection

38. Miscellaneous group

39. Uses and techniques of LA
Surface anaesthesia
 Applied topically on mucous membranes and
abraded skin.
 Superficial layer is anaesthetised and motor
function not affected.
 Onset and duration -site, the drug, conc and
form.
 Lidocaine (10%) sprayed in the throat acts in
2–5 min and produces anaesthesia for 30–45
min.

40.  Adr no affect on duration of topical
anaesthesia.
 Phenylephrine can cause mucosal
vasoconstrion.
 Absorption of soluble LAs from mucous
membranes is rapid, may attain IV conc.
 Eutectic lidocaine/prilocaine is capable of
anaesthetizing intact skin.

41. Sites & uses of SA

42. Infiltration anaesthesia
 Dilute sol of LA is injected under the skin to
reach sensory nerve terminals.
 Uses; minor surgical procedures like incisions
& excisions.
 Onset of action is almost immediate.
 Duration:lidoc 30-60 min, bupiva 90-180 min.
 Motor function is not affected.

43. Conduction block anesthesia
 LA injected around the nerve trunk.
 Area distal to injection site is anesthetized &
paralysed.
 Lidocaine (1–2%) with intermediate duration
of action is most commonly used,
 Longer lasting anaesthesia bupivacaine may
be selected.
Two types
 Field block
 Nerve block

44. Field block
 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.

46. Nerve 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,
etc.
 Used for tooth extraction, operations on
eye, limbs, abdominal wall, fracture setting,
trauma to ribs, neuralgias, persistent
hiccup, etc

48. Spinal anaesthesia
 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.

49.  Spinal anaesthesia is used for operations on
the-lower limbs, pelvis, lower abdomen, e.g.
prostatectomy,
 Fracture setting, obstetric procedures,
caesarean section, etc
 Advantages of spinal anaesthesia over GA
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

51. Complications of spinal anaesthesia
Respiratory paralysis
 Due to Hypotension and ischaemia of
respiratory centre.
Hypotension
 due to blockade of sympathetic outflow to
blood vessels & venous pooling.
 Raising the foot end overcomes the
hypotension.
 Prevented by ephedrine, mephentermine.
Headache
Septic meningitis

52. Cauda equina syndrome
 Prolonged loss of control over bladder and
bowel sphincters.
 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
abdominal viscera.
 Premedication with opioid analgesics prevents
it.

53. Epidural anaesthesia
 LA injected in dural space, acts on nerve
roots.
Thoracic
 Injection is made in the midthoracic region.
 Epidural space in this region is relatively
narrow.
 Analgesia obtained in middle and lower
thoracic dermatomes.
Lumbar
 epidural space is wide.
 Produces anaesthesia of lower abdomen,
pelvis and hind limbs.
 Use is similar to that of spinal anaesthesia.

54. Caudal
 Injection is given in the sacral canal through
the sacral hiatus.
 Produces anaesthesia of pelvic and perineal
region.
 Used mostly for vaginal delivery, anorectal and
genitourinary operations.
Complications
 Cardiovascular complications are similar to
spinal.
 Headache & neurological complications are
less.

55. Intravenous regional anaesthesia