Transcript EO_005.08_part 1 Principals of Local Anesthetics

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Local Anesthetics
PA Course
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Learning Objectives
• To understand the mechanism of action of local
anesthetics
• To understand indications, contraindications, and
adverse effects of local anesthetics
• To be able to select an appropriate local
anesthetic (practical applications will will covered
in next lecture)
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Local Anesthetics
• Work by blocking the generation and
propagation of nerve impulses when applied
locally in adequate concentrations.
– Blocks sodium channels
• This block is reversible thus normal function
returns to the nerve when the local anesthetic
is removed by the blood stream.
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Nerve Impulse Transmission
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Ionized
Extracellular solution
LA
LA
H+
H+
LA+
LA+
LA
+++
Voltage sensor
LA+
Hydrophilic
Pathway
-70 mV
-15 mV
Intracellular Solution
Local Anesthetics Binding Sites
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pKa, pH and Why They Matter
• pKa = pH at which ionized and non-ionized
base are equally present. LA’s are weak
bases with pKa of 8- 9.
• Onset of action related to amount of LA
present as base form.
• As environment becomes more acidic (lower
pH/ more H+ ), equilibrium shifts to the
cationic form, which does not diffuse readily
in to the nerve.
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Pharmacologic Actions
Order of blockade of nerves depends on
• Nerve size (from small to big: C, B, Ad, Ag,Ab,Aa)
• Myelination
Sequence of nerve loss
Loss of pain
Temperature
Touch
Proprioception
Skeletal muscle tone
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Desirable Properties of Local Anesthetics
• Reversiblility
• Non-irritating to tissues
• Rapid onset of action
• Long duration of action (to facilitate procedures)
• High therapeutic index
• Effective topically and by injection
• Ideal physical properties (solubility and stability)
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General Anesthetic Structure
2
1
hydrophobic
3
hydrophilic
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Classification of Anesthetics
esters
amides
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Esters
• Not very stable in solution; easily
broken down by sunlight, heat
• Metabolized by cholinesterases in blood
and skin. Para-aminobenzoic acid
(PABA) is a by-product of metabolism
• Examples: benzocaine, cocaine,
procaine, tetracaine
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Amides
• Long duration of effect
• Cleared from the site of anesthesia by
local blood flow, then metabolized by liver
to water soluble products which are
removed by the kidney
• Fairly stable in solution
• Examples: articaine, bupivacaine,
lidocaine, mepivacaine, prilocaine &
ropivacaine.
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Allergy to LA’s
• Esters may cause allergy due to para-
aminobenzoic acid, which is a breakdown
product of all these agents. Thus allergy to
one ester means allergy to all esters.
• Allergy to an amide is very rare.
• History of allergy to an ester or another amide
does not rule out use of an amide.
• Most “allergy” to dental LA is psychogenic
(anxiety reaction to dental procedure)
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Physicochemical properties
Determines potency, onset and duration of action
1. pKa, dissociation constant
• Proportion of ionized to non-ionized molecules
• Correlates with onset
• Equilibrium exists
• low pH = more in ionized state & unable to cross
membrane
• Sodium bicarbonate –  pH and non-ionized base =
faster onset
• Acidic tissues (ie septic) -  ionized = slower entry
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Physicochemical properties
2. Lipid solubility - Correlates with potency
• Higher solubility = more potent, thus can
use smaller dose (more molecules
penetrate into axioplasm)
3. Protein binding - Correlates with
duration of action
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Increased binding = longer duration of
action
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LA and Blood Flow
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Vasodilation: affects duration of action. At
clinically useful concentrations, the LA’s
(except cocaine) are vasodilators.
Inhibiting blood flow increases duration of the
block- done deliberately during IV regional
anesthesia, or may be a result of circulatory
impairment.
Vasoconstrictors added to LA for this effect.
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Epinephrine
• Most common vasoconstrictor used with
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local anesthetics
Prolongs duration of anesthesia
Increases the intensity of blockade
Reduces systemic absorption of LA
Reduces surgical bleeding
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Epinephrine
• Solutions of
epinephrine containing 5
mcg/ml (1:200,000) appear to be
optimal for the reduction of surgical
bleeding and systemic absorption of
local anesthetics
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Epinephrine
Manifestations of systemic epinephrine
absorption
• Increased heart rate.
• Increased cardiac output.
• Decreased systemic vascular resistance – confusing,
but small vessels in skin, mucosa and viscera are
constricted, while vasculature of skeletal muscles
relaxes
Warning
epinephrine is light and heat sensitive. It oxidizes
easily: do not use if pinkish or brownish in color or if a
precipitate is visible.
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Epinephrine
Contraindications to the addition of
epinephrine
• Peripheral nerve blocks in areas that may lack
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collateral blood flow (penis, digits)
Unstable angina
Cardiac dysrhythmias
Uncontrolled hypertension
Treatment with monoamine oxidase (MAO) inhibitors,
tricyclic antidepressants or sympathomimetics
Uteroplacental insufficiency
Intravenous (IV) regional anesthesia
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Routes of Administration of LA
• Topical/surface
– Skin, mucous membranes, eye,
– ointments, drops, lozenges, gels, creams, sprays
– Many OTC
• Injection
– Infiltration
– Regional
– Intrarticular
– Epidural
– Spinal
– Intravenous
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Systemic absorption
• Rate of systemic absorption depends on
route
fast
slow
Intravenous
Tracheal
Intercostals
Caudal
Paracervical
Epidural
Brachial plexus
Sciatic/femora
Subcutaneous
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Clinical Uses
Topical/Surface
• Used to relieve pain and itching of sunburn,
insect bites, skin abrasions, hemorrhoids,
needle sticks, teething etc. This type of use
is not generally recommended, since there is
risk of sensitization/ absorption, and other
drug or non drug measures are available.
• Numb area prior to dental procedures, other
diagnostic procedures
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Clinical Uses
Infiltration (used for superficial surgery)
– Removal of moles, warts, sebaceous cysts
• Used for IV insertion
• Regional block
• Intravenous
• Epidural
• Spinal
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Spinal Anesthesia
• These products contain NO
ANTIMICROBIAL PRESERVATIVE.
They are in single-dose vials.
• spinal products are hyperbaric due to
addition of dextrose. The patient is
positioned so that anesthesia is
achieved at the appropriate nerve roots
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Drug Interactions
• With topical or infiltration anesthesia, interactions are
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unlikely, since systemic absorption should be very
low.
Inhalation anesthetics and general anesthetic premeds
MAOI’s : increase risk of hypotension
Neuromuscular blockers: LA may enhance/ prolong
action
Cholinesterase inhibitors increase likelihood of
toxicity with ester LA’s
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Adverse Effects of LA’s
• Hypersensitivity
– Usually due to preservative or metabolite of ester
– Skin rash, contact dermatitis, asthmatic attack,
anaphylactic
• Musculoskeletal
– Local anesthetics are myotoxic when injected
directly into skeletal muscle
• Respiratory
– Lidocaine depresses the hypoxic drive
– Apnea can result from phrenic and intercostal
nerve paralysis or depression of medullary centre
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Central Nervous System
Concentration
Toxicity
Low
Circumoral paresthesia, mild
relaxation/sedation, generalized analgesia
Moderate
Euphoria, lightheadedness, dysphoria,
slurred speech, drowsiness, sensory
changes (blurred, double vision), twitching
Moderate to High
Disorientation, tremor, unconsciousness,
seizures
High
Coma, respiratory arrest
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Vascular & Cardiac Effects of
LA’s
• Cocaine causes an intense vasoconstriction which can
lead to destruction of tissue by reducing blood supply
• Other local anesthetics show an initial vasoconstriction,
then vasodilation
• Higher concentrations decrease cardiac conduction
velocity, automaticity, contractility, cardiac output and
blood pressure = cardiovascular collapse. Normally,
there will be signs of CNS toxicity first; these cardiac
effects occur at high plasma concentrations.
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Special Populations
• Pregnancy: no good studies, but
retrospective analyses show no risk to fetus.
LA’s do cross the placenta.
• Breast feeding: some distribution into breast
milk, but appears safe.
• Infants: under 9 months, have low plasma
protein concentrations, which may enhance
effects of bupivicaine. Lidocaine preferred.
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Individual Agents…
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Bupivacaine (Marcaine®)
• Onset of action: intermediate (slower than
lidocaine)
• Duration of action: long (3 to 10 hours)
• Products: available as 0.25% and 0.5%
solutions, with and without epinephrine, in
various volumes and containers. Multidose vials
contain parabens; products with epinephrine
also contain Na metabisulfite (antioxidant)
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Bupivicaine Dosing (Adult)
• Based on healthy, 70 kg young male
• Peripheral nerve block: 12.5 to 175 mg
(5 to 70 mL of 0.25% soln)
• Local infiltration: up to 175 mg (70 mL)
of 0.25% solution without epi.
• If using epi, max dose = 225 mg.
• Total daily doses may go up to 400 mg.
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Lidocaine Parenteral Solution
(Xylocaine®)
• Rapid onset; duration 1 to 3 hours.
• Products:
• 1% and 2 % parenteral solutions, with and without
epi. Note that the multidose vials contain parabens,
but are to be discarded 3 days after initial puncture.
Use single dose vials and discard remaining solution
if possible. Sodium metabisulfite present in the “with”
solutions.
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Lidocaine Parenteral Solution
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Adult dose:
• Digits (no epi !): 1 to 5 mL of 1% solution (onset fast,
within 2- 5 minutes)
• local infiltration: less than 40 mL of 1% solution (onset
within 1-2 minutes)
• Percutaneous: less than 30 mL of 1% solution
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Lidocaine Endotracheal
• Gives surface anesthesia for procedures
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involving nasal/ respiratory tracts
Delivers 10 mg/ spray
New canisters must be primed (5 to 10
pumps). Don’t need to re-prime after
changing nozzle, just void air.
For procedures in oropharynx, 2 to 6 sprays.
For intubation, 5 sprays to 40.
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Lidocaine 2% Jelly
• For surface anesthesia/ lubrication of urethra (ie
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during catheterization); proctoscopy, rectoscopy,
endoscopy.
Not effective on intact skin
Endotracheal intubation: about 2 mL applied to end of
trach tube
Female urethra: 5 to 10 mL
Male urethra: about 20 mL for entire surface; 5 to 10
mL for anterior portion
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Lidocaine 2% Viscous
• For topical anesthesia of mouth and pharynx, surface
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anesthesia with introduction of instruments into
digestive/ resp tracts, pain due to esophagitis
“pink lady” = mixed with Diovol
For mouth and throat: 5 to 10 mL; swish and spit or
swallow slowly
For esophagitis: 5 to 15 mL, swallowed in a single
gulp
Max 60 mL in 24 hours
Onset within 5 minutes; lasts 20 to 30 minutes
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Lidocaine Topical 5%
• Comes in 50 mL plastic bottles;
spearmint flavoured.
• For pain due to inflamed tissue in
mouth, or for surface oral anesthesia for
dental procedures
• 1 to 4 mL applied with a cotton swab
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Lidocaine/ Prilocaine Topical
EMLA: Eutectic Mixture of Local Anesthetics
Intact skin: anesthesia for needle insertion or for superficial
surgical procedures. Used, especially in children, to
reduce pain of vaccination. OK with MMR, DPTP, Hib,
Hep B.
Leg Ulcers: cleansing and debridement
Genital Mucosa: surface anesthesia for short surgical
procedures or infiltration anesthesia
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Lidocaine/ Prilocaine Topical
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DO NOT USE FOR:
application to mucus membrane except for adult genital
mucosa.
Application inside the ear due to possibility of ototoxicity
Area around the eyes; it irritates the cornea
Infants less than 3 months old
infants predisposed to methemoglobinemia; this includes
those receiving sulfonamides.
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EMLA Application
• Intact skin: cream applied thickly to area;
occlusive dressing applied; or may use patch
form. Area is cleaned prior to procedure.
After 1 hour, get about 3 mm depth of
anesthesia.
• Genitalia: cream applied without occlusion;
anesthesia occurs in 5- 10 minutes
• Leg ulcers: apply up to 10 g; remove after 30
to 60 minutes and clean/ debride.
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SUMMARY
Choice of Ideal LA for Indication:
 Quick onset
 Appropriate duration
 Lowest toxicity
 Highest specificity
 Minimize allergic potential