Local Anesthetics

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LOCAL ANESTHETICS
Jeffrey Groom, PhD, CRNAAnesthesiology Nursing
ProgramNGR 6174 Pharmacology of Anesthesiology
Nursing II
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LOCAL ANESTHETICS

• What role do LAs play in anesthesia?
• How are LAs classified?
• How can the LA name identify the class?
• How are LAs metabolized?
• How are nerve impulses conducted?
• What is the mechanism of action of LAs?
• Discuss allergy to LAs

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LOCAL ANESTHETICS

• What determines LA potency?
• What determines LA duration of action?
• What determines LA onset time?
• How does onset proceed?
• Why didnt LA work in a septic wound?
• What is ion trapping?
• How is toxic limit of LA established?
• Why add a vasoconstrictor agent to LAs?
• How does a patient become toxic? SS?
• How is anatomic site related to absorption?

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LOCAL ANESTHETICS USE - topical (skin,
mucosa) SQ Infiltration Intravascular Peri
pheral nerve Epidural space Spinal ACTION -
central or site specific TOXICITY - therapeutic
index
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Local Anesthetics Target Site of Action Local vs
Systemic
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Classification, Structure and Function
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ANESTHETICS
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CONDUCTION of a NERVE IMPULSE
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Conduction Blockade
LAH LAIonized Nonionized
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SEQUENCE OF EVENTS WHICH RESULT IN CONDUCTION
BLOCKADE
1. Diffusion of the base (nonionized) form across
the across the nerve sheath and nerve membrane 2.
Re-equilibration between the base and cationic
forms in the axoplasm 3. Penetration of the
cation into and attachment to a receptor site
within the sodium channel. 4. Blockade of the
sodium channel
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SEQUENCE OF EVENTS WHICH RESULT IN CONDUCTION
BLOCKADE
5. Inhibition of sodium conduction 6. Decrease in
the rate and degree of the depolarization phase
of the action potential 7. Failure to achieve the
threshold potential 8. Lack of development of a
propagated action potential 9. Blockade of
impulse conduction
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Ionized
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Common features of Local Anesthetics

• Weak bases (pKa gt 7.4) poorly water soluble
• Packaged as an acidic hydrochloride pH 4-7 now
  soluble
• In solution- non-ionized lipid soluble (free
  base) AND ionized water soluble (cation)
• Body buffers raise the Ph, increase free base
• lipid soluble form crosses axonal membrane
• water soluble form blocks sodium channel

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Important Clinical Properties of Local Anesthetics

• ONSET
• POTENCY
• DURATION OF ACTION

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Important Clinical Properties of Local Anesthetics

• ONSET pKa
• pKa pH at which 50 of drug is ionized
• LAs lt50 exists in the lipid soluble nonionized
  form
• Only the nonionized form crosses into the nerve
  cell

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ROLE of pH and pKa in LOCAL ANESTHETICS
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Important Clinical Properties of Local Anesthetics

• Speed of Onset
• low pKa fast onset
• Bupivacaine 8.1Lidocaine 7.7
• ? LA action in septic tissue
• acid tissue -gt é ionized of LA-gt slow entry
  into membrane -gt low concentration of LA for
  block

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Important Clinical Properties of Local Anesthetics

• Anesthetic Potency
• Potency ltgt lipid solubility
• Higher solubility ltgt can use a lower
  concentration and reduce potential for toxicity
  LA

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Important Clinical Properties of Local Anesthetics

• DURATION OF ACTION
• Duration ltgt protein binding
• Bupivacaine 95Lidocaine 65Procaine 6

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Important Clinical Properties of Local Anesthetics

• CLEARANCE
• ESTERShydrolysis via pseudocholinesterase
• AMIDESmetabolism via hepatic enzymes

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Properties of Local Anesthetic Agents

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Important Clinical Properties of Local Anesthetics

• INCREASED DOASGE
• Intensity Duration ltgt INCRESED
• Increase dose via increased volume or
  concentration of LA

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Important Clinical Properties of Local Anesthetics

• Absorption of local at site
• LAs cause some vasodilitation _at_ site
• LA washout related to blood flow
• LA toxicity related to rate of absorption via
  blood flow

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Important Clinical Properties of LAs

• ADDITION of VASOCONSTRICTORS
• Vasoconstriction ltgt slows systemic absorption
  é duration
• Epi 1200,000 or 5 mcg/ml
• Least effective with high lipid soluble LAs
  (bupivacaine/etidocaine)
• Epi may produce distal and systemic effects

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Important Clinical Properties of LAs

• ADDITION of Sodium Bicarbonate
• NaHCO3 - é pH nonionized base
• Speeds onset of block
• 1 mEq NaHCO3 per 10 ml Lido/Mepiv
• .1 mEq NaHCO3 per 10 ml Bupiv

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Nerve Fiber and Local Anesthetic Effects

• Fiber diameter - larger the fiber the higher the
  concentration of LA required
• Myelination - LA
• Position in nerve bundle - mantle -gt core
• Mantle fibers innervate PROXIMAL nerves
• Core fibers innervate DISTAL nerves

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Nerve Fiber and Local Anesthetic Effects
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Nerve Fiber and Local Anesthetic Setup

• Sequence of clinical anesthesia
• Sympathetic block (vasodilate éskin T0)
• Loss of pain and temperature sensation
• Loss of proprioception
• Loss of touch and pressure sensation
• Loss of motor function

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Local Anesthetic Toxicity

• Local vs Systemic
• Neuro vs Cardiovascular
• Concentration and Rate of Absorption vs rate
  of metabolism
• Toxicity limits (and epi concentrations)
• Clinical scenarios - toxicity risk increased
• Symptoms
• Management

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Local Anesthetic Toxicity
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LOCAL ANESTHETICS

• What role do LAs play in anesthesia?
• How are LAs classified?
• How can the LA name identify the class?
• How are LAs metabolized?
• How are nerve impulses conducted?
• What is the mechanism of action of LAs?
• Discuss allergy to LAs

36
LOCAL ANESTHETICS

• What determines LA potency?
• What determines LA duration of action?
• What determines LA onset time?
• How does onset proceed?
• Why didnt LA work in a septic wound?
• What is ion trapping?
• How is toxic limit of LA established?
• Why add a vasoconstrictor agent to LAs?
• How does a patient become toxic? SS?
• How is anatomic site related to absorption?