Transcript Local Anesthetics (PPT) - SIU School of Medicine

Local Anesthetics
Joseph Haake, MS4
February 21, 2007
Types of Local Anesthetics
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Esters
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Procaine
Cocaine
Tetracaine
Chloroprocaine
Queen
Others
Diphenhydramine
Benzyl alcohol
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Amides
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(i in prefix)
Lidocaine
Bupivacaine
Mepivacaine
Etidocaine
Prilocaine
Ropivacaine
Chemical Structure
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Most esters and amides are synthetic
derivatives of cocaine
Consist of:
• Aromatic head (lipophilic)
• Terminal amine tail (hydrophobic)
• Hydrocarbon chain attached to the aromatic
acid (via amide or ester bond)
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Metabolism
• Esters: hydrolysis in plasma
• Amides: biotransformation via liver
Mechanism of Action
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Block transmission of action potential
by binding to voltage-gated sodium
channels
Anesthesia occurs when enough drug
molecules occupy sodium channels to
interrupt and temporarily stop
conduction
Activity is based on pKa, lipid
solubility, and protein binding
Clinical Characteristics
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Onset
• pKa: lower pKa results in faster travel thru lipid
layers → faster onset
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Potency
• Lipid solubility: higher lipid solubility results in
increased concentrations inside nerve → higher
potency
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Duration
• Protein binding (affinity LA has for Na
channel): higher affinity → longer duration
Clinical Characteristics of Common
Local Anesthetics
Drug
Onset
(min)
Duration
(min)
Potency
(relative)
Procaine
2-5
15-45
1
Lidocaine
2-5
30-60
2
Bupivacaine 3-7
90-360
8
Mepivacaine 3-7
90-180
2
Friends of Locals
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Epinephrine
• Added to provide longer duration of
anesthesia, promote hemostasis, & slow
systemic absorption
• May increase pain of injection by lowering pH
• Avoid in “end-arterial fields” (digits, nose,
ears, penis); if trouble arises, apply nitro paste
or inject intravascular phentolamine
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Sodium Bicarbonate
• Mix with lidocaine (9 mL lido 1% to 1 mL
bicarb 8.4%)
• Increases pH, thus faster diffusion into nerve &
faster onset of action
Differential Nerve Blockade
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Large, myelinated nerve fibers more
sensitive to blockade than smaller,
unmyelinated fibers
Anesthetics diffuse from the outer surface
toward the center after deposition near a
peripheral nerve
• Proximal anesthesia occurs before distal (e.g.
axillary block produces anesthesia of shoulder
before hand)
• Skeletal muscle paralysis may precede sensory
blockade
Toxicity
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Systemic toxicity often results from high
plasma concentrations
Related to potency (lipid solubility) &
duration of action (protein binding)
Often from accidental intravascular
injection
Less likely from local absorption
• Dependent on vascularity (high vascularity =
high absorption)
• Vascularity of common sites: intercostal >
epidural/caudal > brachial plexus > mucosal >
distal peripheral nerve > subcutaneous
Systemic Toxic Effects
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CNS
• Visual change, numb tongue, lightheadedness,
restlessness
• Perioral paresthesia, muscle twitch, slurred speech,
excitability, drowsiness
• Seizures, cardiorespiratory depression, coma
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Cardiovascular
• Palpitations, vasodilation, HTN, ventricular arrhythmias,
myocardial depression, hypotension, bradycardia, cv
collapse
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Respiratory
• Hypoventilation, resp arrest
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Allergy
• More common in esters
Questions?
Sources
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Tintinalli JE, Kelen GD and
Stapczynski JS. Emergency Medicine:
A Comprehensive Study Guide.
American College of Emergency
Physicians. 6th ed. 2004.
Stoelting RK and Miller RD. Basics of
Anesthesia. Churchill Livingstone /
Elsevier. 5th ed. 2007.