1. LOCAL ANESTHETICS
DR SEEMI GULL
ASSOCIATE PROFESSOR

2.  t1/2 Elimination (h) Vdss (L) CL (L/min)
 Bupivacaine 28 3. 5 72 0.47
 Lidocaine 10 1.6 91 0.95
 Mepivacaine 7 1.9 84 0.78
 Prilocaine 5 1.5 261 2.84
 Ropivacaine 23 4.2 47 0.44
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3. Local Anesthesia:

 Definition: Local anesthesia is any technique to
render part of the body insensitive to pain without
affecting consciousness.
 LOCAL ANESTHETICS
These are are the agents which produce transient and
reversible loss
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4. CONTINUED
The following terms are often used interchangeably:
 Local anesthesia, is anesthesia of a small part of
the body such as a tooth or an area of skin.
 Regional anesthesia is aimed at anesthetizing a
larger part of the body such as a leg or arm.
 Conduction anesthesia is a comprehensive term
which encompasses a great variety of local and
regional anesthetic techniques.
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5. Local anesthetics:
amides vs. esters
 Common structure
 Aromatic ring
 Tertiary amine
 Alkyl chain
 Linking bond
 Amide bond
(see lidocaine)
 Ester bond
(see procaine)
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6. Types of Local Anesthetics
ESTERS:
 Procaine
 chloroprocaine
 tetracaine
 Cocaine
 Benzocaine
AMIDES:
 Etidocaine (Duranest)
 Lidocaine (Xylocaine)
 Mepivacaine (Carbocaine)
 Prilocaine (Citanest)
 Ropivacaine
 Bupivacaine (Marcaine)
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7. Pharmacokinetics:
 PKa And Onset of Action:
 Local anesthetics with a pKa closest to physiological
pH will have a higher concentration of nonionized
base that can pass through the nerve cell membrane,
and generally a more rapid onset.
 pKa > 7.4 more cations, pKa < 7.4 more anions
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8. Duration and Protein binding:
Amides: Esters:
 Bupivacaine, Etidocaine Chloroprocaine and
and Ropivacaine- very Procaine- have low potency
high potency and lipid and lipid solubility and also low
solubility, very long duration and protein binding.
duration and protein
binding also. Cocaine- has intermediate
 Lidocaine, Prilocaine potency and solubility and
and Mepivacaine- have intermediate duration and
intermediate potency protein binding
and lipid solubility and Tetracaine- has high potency
intermediate duration of
action and protein and lipid solubility along with a
binding. long duration of action and
high protein binding
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9. Systemic absorption
Rate of systemic absorption:
 Intravenous > tracheal > intercostal > caudal > paracervical >
epidural> brachial plexus > sciatic > subcutaneous
 High tissue binding also decreases the rate of absorption
Metabolism:
 Amides…
N-dealkylation and hydroxylation
 P-450 enzymes, liver, slower process than esterase activity
 Prilocaine>lidocaine>mepivacaine>ropivacaine>bupivacaine
 Esters…
 Pseudocholinesterase
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10. Pharmacokinetics:
AGENT Pot. Onset pKa %PB P. coef
Procaine 0.5-1% (Novocain) 1 Rap 8.9 5.8 0.02
Chloroprocaine 2-3% (Nesacain) 4 Rap 8.7 ? 0.14
Tetracaine 0.1-0.5% (Pontocain) 16 Slow 8.5 75.6 4.1
Lidocaine 1-5% (Xylocaine) 1 Rap 7.9 64.3 2.9
Mepivacaine 1.5% (Carbocaine) 1 Mod 7.6 77.5 0.8
Bupivacaine 0.25-0.75% (Marcainesensorcaine) 4 Slow 8.1 95.6 27.5
Etidocaine 0.5-1.5% (Duranest) 4 Rap 7.7 94 141
Prilocaine 1 7.9 55 0.9
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Ropivacaine 0.75% (Naropin) 4 Mod 8.1 94 2.9

11. Mechanism of Action
 Voltage & time dependent blockade of resting
membrane sodium channels
 binding to sodium channel receptors inside the cell
 Inc threshold for excitation
 Slowing of impulse conduction
 Decreased rate of rise of action potential
 inhibiting action potentials in a given axon.
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14. CONTINUED
 If the resting potential encounters the proper
chemical, mechanical or electrical stimuli to reduce
the membrane potential to less than -55 mV then an
action potential is produced that allows the influx of
sodium ions. LA act here to block the Na influx.
 The influx allows the membrane potential to further
increase to +35mV temporarily.
 Sodium and potassium channels along with the
sodium/potassium pump eventually returning a given
axon back to it’s resting membrane potential after an
action potential.
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15. Regional anesthesia
 Definition:
Rendering a specific area of the body, e.g. foot, arm,
lower extremities, insensate to stimulus of surgery or
other instrumentation
Uses:
 Provide anesthesia for a surgical procedure
 Provide analgesia post-operatively or during labor
and delivery
 Diagnosis or therapy for patients with chronic pain
syndromes
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17. Types:
 Application of local
anesthetic to mucous
membrane - cornea,
nasal/oral mucosa:
 Uses :
 awake oral, nasal
intubation, superficial
surgical procedure
 Advantages :
 technically easy
 minimal equipment
 Disadvantages :
 potential for large doses
leading to toxicity
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18. Subcutaneously
 Application of local subcutaneously to
anesthetize distal nerve endings
 Uses:
 Suturing, minor superficial surgery, more
extensive surgery with sedation
 Advantages:
 minimal equipment, technically easy, rapid
onset
 Disadvantages:
 potential for toxicity if large field
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19. IV Block
 Injection of local anesthetic intravenously for
anesthesia of an extremity
 Uses
 any surgical procedure on an extremity
 Advantages:
 technically simple, minimal equipment, rapid
onset
 Disadvantages:
 duration limited by tolerance of pain, toxicity
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20. Peripheral nerve block
 Injecting local anesthetic
near the course of a named
nerve
 Uses:
 Surgical procedures in the
distribution of the blocked nerve
 Advantages:
 relatively small dose of local
anesthetic to cover large area;
rapid onset
 Disadvantages:
 technical complexity
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21. NERVE BLOCK ANESTHESIA
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22. Plexus Blockade
 Injection of local anesthetic
adjacent to a plexus, e.g cervical,
brachial or lumbar plexus
 Uses :
 surgical anesthesia or post-
operative analgesia in the
distribution of the plexus
 Advantages:
 large area of anesthesia with
relatively large dose of agent
 Disadvantages:
 technically complex, potential for
toxicity and neuropathy.
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23. PLEXUS BLOCK
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24. Central neuraxial blockade - “Spinal”
 Injection of local anesthetic into
CSF
 Uses:
 profound anesthesia of lower
abdomen and extremities
 Advantages:
 technically easy, high success
rate, rapid onset
 Disadvantages:
 “high spinal”, hypotension due to
sympathetic block, post dural
puncture headache.
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27. SPINAL ANESTHESIA
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28. Central Neuraxial Blockade -
“epidural
 Injection of local anesthetic in to
the epidural space at any level of
the spinal column
 Uses:
 Anesthesia/analgesia of the
thorax, abdomen, lower
extremities
 Advantages:
 Controlled onset of blockade, long
duration when catheter is placed,
post-operative analgesia.
 Disadvantages:
 Technically complex, toxicity,
“spinal headache”
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29. 29

30. Systemic Toxicity of Local
Anesthetics
 Drugs-not a great difference in toxicity
between equally potent local anesthetics-one
of low toxicity when a large dose is required
 Site of injection-vascular sites lead to rapid
absorption
 accidental I.V. injection is the most common
cause of toxicity
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31. Signs and Symptoms of
Local/Regional Anesthesia Toxicity
CNS Toxicity:
 Unconsciousness
 Generalized convulsions
 Coma
 Apnea
 Numbness of the mouth and tongue, metal taste
in the mouth
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32.  Light-headednes
 Tinnitus
 Visual disturbance
 Muscle twitching
 Irrational behavior and speech
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33. Cardiovascular toxicity
 slowing of the conduction in the myocardium
 myocardial depression
 peripheral vasodilatation
 usually seen after 2 to 4 times the convulsant dose
has been injected
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34. Hypersensitivity/Allergy:
true allergy is very rare.
 esters ---- sensitivity to their metabolite, para-
aminobenzoic acid (PABA), and does not result in
cross-allergy to amides..
 allergy to paraben derivatives, which are often added
as preservatives to local anesthetic solutions.
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35. Methemoglobinemia:
 prilocaine metabolite, o-toluidine, is known to
cause methemoglobinemia.
 .
 Seen with larger not recommended for use in
infants.
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36. Prevention and Treatment of
Local/Regional Anesthesia Toxicity
Prevention:
 use recommended dose
 Aspirate through the needle or catheter
before injecting the local anesthetic.
 large quantity required, divide the dose into
small increments, increasing the total
injection time
 inject slowly (<10 ml/min)
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37. Treatment:
 Manage airway and give oxygen
 Stop convulsions if they continue for more
than 15 to 20 seconds
 Thiopental 100 mg to 150 mg IV
 or Diazepam 5 mg to 20 mg IV
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38. Drug Interactions
 Chloroprocaine may interfere with the analgesic
effects of intrathecal morphine
 Opioids and α2 agonists potentiate LA’s
 Propranolol and cimetidine decrease hepatic blood
flow and decrease lidocaine clearance
 Pseudocholinesterase inhibitors decrease Ester LA
metabolism
 Dibucaine (amide LA) inhibits pseudocholinesterase
used to detect enzyme
 potentiate nondepolarizing muscle relaxant blockade
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39. THE END
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