Lecture slides for undergraduates medical (MBBS) Students. Source material for this presentation is Essentials of Pharmacology, KD Tripathi, Katzung and Goodman and Gillman. It deals with Local anaesthetics with their mechanism of action, pharmacokinetics , adverse effects and therapeutic uses.

1. Local
Anaesthetics
Dr Mayur Chaudhari
Assistant Professor
Department of Pharmacology
Government Medical College, Surat
Available at www.slideshare.net
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2. At The End Of Class…..
• Local Anaesthesia
• Mechanism of Action
• Pharmacodynamic
• Pharmacokinetic
• Individual Agents
• Techniques and uses
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3. Local Anaesthesia
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4. Local Anaesthesia
• Reversible loss of sensation (Sensory)
• In a local area
• Without loss of consciousness
• Without loss of control of vital functions
• Topical/Injection/Infiltration
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5. Ideal Local Anaesthetic
Non irritant / Negligible Local irritation
 Negligible local tissue damage
 minimal systemic toxicity
Rapid onset of action
Prolonged action
 water soluble
 Sterilizable by heat
Without after effects
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6. Local Vs General
Advantages
Disadvantages
•
•
•
•
•
•
• Uncooperative patient –
No
• Minor Surgery only
• Some major Surgery
• Also Have Side effects
Consciousness
Localized
No Altered Physiology
Monitoring of Vitals
Safe in poor GC
Response can be
modified
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7. Historical Aspects
• South American natives chewed coca leaves
for stimulant and euphoric action
• Albert Niemann – isolated cocaine in 1860
• Niemann noted that it causes numbing of
tounge
• Sigmund Freud – tried it for psychic energizing
activity unsuccessfully
• Carl Koller – used cocaine for Ocular surgery
in 1884
• Halstead – infiltration anaesthesia
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8. Classification
 Injectable
 Low Potency, Short Duration
Procaine, Chloroprocaine
 Intermediate Potency and Duration
Lignocaine, Prilocaine
 High Potency, long Duration
Tetracaine, Bupivacaine, Ropivacaine, Dibucaine
 Surface Anaesthetic
 Soluble: Cocaine, Lignocaine, Tetracaine, Benoxinate
 Insoluble: Benzocaine, Butamben, Oxethazaine
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9. Classification - II
Ester Linked
Amide linked
• Cocaine, Procaine,
Chloroprocaine,
Tetracaine
• Lignocaine,
Bupivacaine, Prilocaine,
Ropivacaine
– Short acting
– Metabolized by plasma
esterase
– Can be used in poor liver
function
– Hypersensitivity - ↑
– Longer acting
– Metabolized by liver
enzymes
– Avoided in poor liver
function
– Hypersensitivity - ↓
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10. Mechanism Of Action
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11. Mechanism Of Action
 Prevent generation and conduction of Nerve
impulses by acting at the cell membrane:
 Decrease the entry of Na+ ions during action
potential
 Increase in LA conc. decreases the maximum
depolarization causing slowing of conduction
 Finally depolarization fails to reach threshold
potential
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12. Mechanism Of Action
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13. Mechanism Of Action
Degree of blockade is frequency dependent:
Greater blockade at higher frequency of
stimulation
Higher concentration of Ca++ reduces
inactivation of Na+ channel
Blockade is not due to hyperpolarization
RMP is unaltered as K+ channels are not
blocked
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14. Factors Influencing Action of LA
 Lipid Solubility
 Lipid solubility helps in nerve penetration, faster action
 Non ionized form can easily cross nerve membrane
pH
 Lower pKa (7.6 – 7.8) – faster acting (lidocaine, mepivacaine)
 Higher pKa (8.1 – 8.9) – slower acting (procaine, tetracaine,
bupivacaine)
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15. Factors Influencing Action of LA
 Vasoconstrictors (Adrenaline, Phenylephrine)
 Tissue Necrosis, Systemic Side effects
 CI in areas with terminal arteries (Fingers, Toe, Nose, Penis)
- Hypoxic injury
- Tissue Necrosis and May Produce gangrene
 Felypressin (Vasopressin Analogue)
- Used as vasoconstrictor in CV Dz Patients
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16. Factors Influencing Action of LA
Inflammation
 Acidic environment
 ionized LA, Penetration decreased
 Alkalization
 Hasten onset of nerve block
 Limited increase in unionized form
 precipitation of LA
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17. Pharmacodynamics
Functions lost by LA (Local)
 Pain perception
 Temperature
 Touch sensation
 Proprioception
 Skeletal muscle tone
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18. Pharmacodynamics
Sensory > Motor
Nonmyelinated > Myelinated
Small fibres > Large fibres
Autonomic fibres > Somatic Fibres
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19. Pharmacodynamics (Systemic)
CNS
• Inhibition of inhibitory neurons
• Euphoria, Dysphoria, Muscle twitches
• Stimulation – Restlessness, tremors, Convulsions
• Respiratory depression in high doses
• Respiratory failure - death
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20. Pharmacodynamics (Systemic)
CVS
• ↓ Automaticity, Conductivity, Excitability,
Contractility, Conductivity
• ↑ Effective refractory period
• Prolonged QTc interval
• Ventricular Tachycardia, Ventricular Fibrillation
• ↓ in Blood Pressure by Sympathetic blockade
• Cocaine ↑ Blood pressure
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21. Pharmacodynamics (Systemic)
Smooth Muscle
• ↓ contraction of bowel
• Relaxation of vascular and bronchial smooth muscle

Sympathetic System
• Blockade – Spinal, Epidural anaesthesia, local
infiltration in peritoneal cavity

Neuromuscular Junction
• Block NMJ, Inhibit ganglionic transmission
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22. Pharmacokinetics
• Surface anesthetics from mucus membrane and
abraded areas
• Depends on Blood flow to the area, total dose and
specific drug characteristics
• Widely distributed in the body: (lipophilic)
• Enters brain, heart, liver and kidney
• Followed by muscle and other viscera
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23. Pharmacokinetics
• Ester linked LA – inactivated by hydrolysis by plasma
esterases, cholinesterase
• Spinal anaesthesia – absorbed into systemic
circulation
• Amide linked LA – Degraded in liver by CYP450
• Use restricted in Liver disease
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24. Pharmacokinetics
• Amide linked LA – bind with α1 acid glycoprotein
• α1 acid glycoprotein (↑) – MI, Trauma, Cancer,
Surgery, Smoking
• α1 acid glycoprotein (↓) – Oral Contraceptive Pill,
Infants
• Termination of action depends on rate of absorption
and elimination
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25. Break Time
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26. Toxicity
 CNS
 Numbness in circumoral area and tongue
 Metallic taste
 Drowsiness, Lightheadedness, Restlessness
 Visual and auditory disturbances, Nystgmus
 Respiratory depression, convulsions
 Death due to respiratory failure
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27. Toxicity
CVS
 Hypotension, Bradycardia, Cardiac Dysrhythmia
 CV Collapse
Methaemoglobinaemia
 Prilocaine and Benzocaine
 AE due to Vasoconstrictor
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28. Toxicity
Hypersensitivity
 Esters> Amides (Methyl Paraben)
 Asthmatic attack
 Allergic dermatitis
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29. Prevention of Toxicity
 Proper History, Allergy Testing
 4 hour fasting, Premedication
 Avoid in Hepatic and cardiac disease
 Administration at Proper site
 Wait for development of effect
 Look for signs of toxicity
 Observation post operatively
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30. Cocaine
Natural alkaloid from Erythroxylon coca
Medical use limited to surface or topical
anesthesia
Avoid with adrenaline
A toxic action on heart may induce rapid and
lethal cardiac failure
Marked pyrexia is with cocaine overdose
Not used presently
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31. Procaine
 Topically ineffective
 Used for infiltration because of low potency and
short duration
 Most commonly used for spinal anesthesia
 Produces significant vasodilation. Adrenaline used to
prolong effect
 Systemic toxicity negligible because rapidly destroyed
in plasma
 Procaine penicillin
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32. Lignocaine
 Effective by all routes.
 Faster onset (3 Vs 15 min), more intense, longer
lasting
 Good alternative for those allergic to ester type
 Quicker CNS effects than others
 Overdose (muscle twitching, cardiac arrhythmia, fall
in BP, coma and respiratory arrest)
 Antiarrhythmic
 Available as Injections, topical solution, jelly and
ointment etc.
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33. Bupivacaine
 No topical effect
 Slower onset and one of longer duration agents
 Used for infiltration, spinal, nerve block and epidural
 Unique analgesia without significant motor blockade
(popular drug for analgesia during labor)
 High lipid solubility, high distribution in tissues and
less in blood (benefit to fetus)
 More cardio toxic than other LA (prolong QT interval)
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34. Eutectic Lignocaine/Prilocaine
 Eutectic Mixture – Lowering of melting point of two
solids when they are mixed
 Lignocaine+Prilocaine at 25o C in equal proportion
 Oil is emulsified in water to form a cream
 Occlusive dressing prior to procedure
 IV Canulation, Split Skin graft harvesting, Superficial
Procedure
 Up to 5mm
 last for 1-2 hour
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35. Benzocaine, Butamben
 Low aqueous solubility – Not absorbed from mucosa
or broken skin
 Long lasting anaesthesia without systemic toxicity
 Lozenges for stomatitis, Sore throat
 Dusting powder on wounds/ Ulcerated surfaces
 Suppositories for anorectal lesions
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36. Techniques
Surface Anaesthesia
 Mucous membranes and abraded skin
 Nose, mouth, bronchial tree, cornea and urinary
tracts
 Lignocaine, Tetracaine
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37. Infiltration Anaesthesia
 Injection of LA directly into tissues irrespective of the
course of nerve
 Superficial or deeper structure
 Amides are preferred
 Should not be injected into
tissues supplied by end arteries
 Adequate anaesthesia without
affecting normal function
 Dose required is more
 Chances of Systemic Toxicity
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38. Field Block
 Injection of LA subcutaneously
 Anaesthetize the region distal to the site of injection
 Anaesthesia starts 2-3 cm distal to site of injection
 All nerves coming to the field are blocked
 Dose required is less, Prolonged duration
 Forearm, anterior abdominal wall, scalp and lower
extremity
 Knowledge of neuroanatomy is required
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39. Nerve Block
 LA injected around individual Nerve/ Plexus..Not in
the Nerve
 Sensory and motor block distal to site of injection
 Block depends on Proximity, Conc. And Volume of LA
 Degree of ionization and Time
 Trigeminal nerve blocks (face)
 Cervical plexus block and cervical paravertebral block
(shoulder and upper neck)
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40. Spinal Anaesthesia
 Subarachnoid space
 between L2-3 or L3-4
 Site of action – nerve root in
the cauda equina
 Level of anaesthesia –
 vol. & speed of injection;
 Baricity of drug soln. with CSF
 Posture of patient
 Order of anaesthesia – sympathetic > motor
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41. Spinal Anaesthesia
 Uses – lower limbs, pelvis, lower abdomen,
prostatectomy fracture setting and obstetric
procedures
 Spinal headache, hypotension, bradycardia and
respiratory depression, cauda equina syndrome and
nausea-vomiting
 Drugs - Lidocaine, Tetracaine
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42. Epidural Anaesthesia
 Site- sacral hiatus (caudal) or lumber, thoracic or
cervical region
 Catheters are used for continuous infusion
 Used like spinal and also painless childbirth.
 Side effect similar to Spinal, Less Chances
 Lidocaine, bupivacaine, Ropivacaine
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43. Regional anaesthesia (IV)
 Injection of LA in a vein of a tourniquet occluded
limb
 Mostly limited to upper limb
 Orthopedic procedures
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44. Summary
-Caine …
Na+ Channel Blockers
Esters and Amides
Local and Systemic Actions (Toxicity)
 Techniques
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