2. What are local anesthetics?
Local anesthetic: produce loss of sensation to pain in a specific area of
the body without the loss of consciousness
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3. History
Genus Erythroxylum discovered in South
America, Venezuela, Bolivia, and Peru since pre-
Columbian periods
Coca leaves from the genus Erythroxylum contain high
concentration of alkaloid up to 0.7-1.8%
In 1571, Pedro Pizarro, a conquistador of Inca, observed
nobles and high rank officials of the Inca empire consumed
the coca plant.
After the fall of the Inca empire, coca consumption spread
widely to the population
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4. Development of general and local
anesthesia
Took place in Western Europe from 1750 to 1850
Chemists and physicians collected sample of coca leaves
for experiments
Isolated active principle of coca leaf, synthesized to a drug
for patients to feel more relief of pain when taking surgeries
In 1860, German chemist Albert Niemann successfully
isolate the active principle of coca leaf; he named it cocaine
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5. Development of general and local anesthesia
(cont.)
Niemann discovered the effect of numbness of the tongues caused by
alkaloid in 1860
Based on Niemann’s discovery, Russian physician Basil Von Anrep
did experiments on animals, such as rats, dogs, and cats.
He injected small quantity of 1% solution to his tongue; tongue
became insensitive
He concluded cocaine is a good drug for surgical anesthetic
William Steward Halsted and Richard John Hall developed the inferior
dental nerve block techniques for dentistry
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6. Cocaine Addiction
An ophthalmologist Carl Koller realized the importance of
the alkaloid’s anesthetic effect on mucous membranes
In 1884, he used the first local anesthetic on a patient with
glaucoma
In 1898, Professor Heinrich Braun introduced procaine as
the first derivative of cocaine, also known as the first
synthetic local anesthetic drug
Trade name is Novocaine®
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7. Procaine replaced cocaine
(Problems)
Took too long to set (i.e. to produce the desired anesthetic
result)
Wore off too quickly, not nearly as potent as cocaine
Classified as an ester; esters have high potential to cause
allergic reactions
Caused high conc. of adrenaline resulted in increasing heart
rate, make people feel nervous
Most dentists preferred not to used any local anesthetic at all
that time; they used nitrous oxide gas.
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8. Lidocaine
In 1940, the first modern local anesthetic
agent was lidocaine, trade name
Xylocaine®
It developed as a derivative of xylidine
Lidocaine relieves pain during the dental
surgeries
Belongs to the amide class, cause little
allergenic reaction; it’s hypoallergenic
Sets on quickly and produces a desired
anesthesia effect for several hours
It’s accepted broadly as the local
anesthetic in United States today
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10. Membrane potential and neurotransmission:
Neuron transmits information mainly by two mechanisms:
– chemical
– and electrical signals.
Information within a neuron is mainly transmitted by electrical signals.
Electrical signals are propagated by the mechanism called action
potential.
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11. neurotransmission: Resting Potential
Resting neurons maintain an intracellular negative membrane
potential.
Na+/K+ ATPase (sodium pump) transports intracellular Na+ to
extracellular in exchange of entry of K+ into cells. This creates a
concentration gradients of Na+ and K+
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12. neurotransmission: Resting Potential
The resting neuron cell membrane contains much more open K+
channels than open Na+ and Cl-
channels or channels for other ions. K+ flows to the outside down the
concentration gradient, resulting in a negative potential inside the cell.
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14. neurotransmission: Action Potential (Depolarisation)
When stimulated (electrically or chemically), a depolarization of the
membrane potential in the neuron (axon) membrane opens voltage-
gated Na+ channels.
This leads to a burst of flow of Na+ into the cell down the
concentration gradient, causing a reverse of the membrane potential
(from negative inside to positive inside).
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16. neurotransmission: Action Potential (Repolarisation)
Eventually, the influx of Na+ is stopped when Na+ concentration
gradient is balanced by the reversed potential gradient.
Na+ channels are closed by the voltage-sensitive regulatory domain
Subsequently, voltage-gated K+ channels open, allowing accelerated
outflow of K+. The membrane potential returns to resting state
Page 16
18. Membrane potential and neurotransmission:
Action potential at one site of the neuron causes partial
depolarization of neighboring region, activates voltagegated
Na+ channels in the neighboring region and thus causes
propagation of the action potential (electrical signals) along
the axon to synapses.
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22. How Local Anesthetics Work
Altering the basic potential of the nerve
membrane
Altering the threshold or firing level
Decrasing the rate of depolarization
Prolonging the rate of repolarization
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24. Differences of Esters and Amides
Two classes of local anesthetics are amino amides and amino esters.
Amides: Esters:
--Amide link b/t intermediate --Ester link b/t intermediate chain and chain
and aromatic ring aromatic ring
--Metabolized in liver and very --Metabolized in plasma
--Cause allergic reactions
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25. Differences of Esters and Amides
All local anesthetics are weak bases. Chemical structure of local anesthetics
have an amine group on one end connect to an aromatic ring on the other and
an amine group on the right side. The amine end is hydrophilic (soluble in
water), and the aromatic end is lipophilic (soluble in lipids)
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26. Structures of Amides and Esters
The amine end is hydrophilic (soluble in water), anesthetic molecule dissolve in
water in which it is delivered from the dentist’s syringe into the patient’s tissue.
It’s also responsible for the solution to remain on either side of the nerve
membrane.
The aromatic end is lipophilic (soluble in lipids). Because nerve cell is made of
lipid bilayer it is possible for anesthetic molecule to penetrate through the nerve
membrane.
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29. Pharmacokinetics
Following injection into the area of nerve fibers to be blocked, local
anesthetics are absorbed into blood.
– Ester-linked local anesthetics are quickly hydrolyzed by butyrylcholinesterase in
blood.
– Amide-linked local anesthetics can be widely distributed via circulation. Amide-
linked local anesthetics are hydrolyzed by liver microsomal enzymes.
Thus, half lifes of these drugs are significantly longer and toxicity is more likely
to occur in patients with impaired liver function.
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30. Pharmacokinetics
Absorption of local anesthetics is affected by following factors:
– dosage,
– site of injection,
– drug-tissue-binding and
– Presence of vaso-constricting drugs
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31. Factors Affect the Reaction of Local
Anesthetics
Lipid solubility
All local anesthetics have weak bases. Increasing the lipid solubility
leads to faster nerve penetration, block sodium channels, and speed up
the onset of action.
The more tightly local anesthetics bind to the protein, the longer the
duration of onset action.
Local anesthetics have two forms, ionized and nonionized. The
nonionized form can cross the nerve membranes and block the sodium
channels.
So, the more nonionized presented, the faster the onset action.
Page 31
32. Factors Affect the Reaction of Local
Anesthetics
pH influence
Usually at range 7.6 – 8.9
Decrease in pH shifts equilibrium toward the ionized form, delaying the
onset action.
Lower pH, solution more acidic, gives slower onset of action
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33. Factors Affect the Reaction of Local
Anesthetics (cont.)
Vasodilation
Vasoconstrictor is a substance used to keep the anesthetic solution in
place at a longer period and prolongs the action of the drug
vasoconstrictor delays the absorption which slows down the absorption
into the bloodstream
Lower vasodilator activity of a local anesthetic leads to a slower
absorption and longer duration of action
Vasoconstrictor used the naturally hormone called epinephrine
(adrenaline). Epinephrine decreases vasodilator.
Side effects of epinephrine
Epinephrine circulates the heart, causes the heart beat stronger and
faster, and makes people feel nervous.
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34. Toxicity
Toxicity is the peak circulation levels of local anesthetics
Levels of local anesthetic concentration administered to patients are varied
according to age, weight, and health.
Maximum dose for an individual is usually between 70mg to 500mg
The amount of dose also varied based on the type of solution used and the
presence of vasoconstrictor
Example:
---For adult whose weight is 150lbs and up, maximum dose Articaine and
lidocaine is about 500mg
---For children, the dosage reduced to about 1/3 to ½ depending on their
weight.
The doses are not considered lethal.
Some common toxic effects:
--light headedness ---shivering or twitching --seizures
--hypotension (low blood pressure)
Page 34 --numbness
35. Drugs used in dental anesthesia
The most common local anesthetic used is called lidocaine.
Others might include mepivacaine, bupivacaine and prilocaine.
All of the drugs will most likely end with a caine. Procaine, which is
commonly known as novacaine is no longer used as the other drugs
mentioned here are more effective as numbing agent.
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36. Drugs used in dental anesthesia
Bupivicaine (Marcaine®
--Produce very long acting anesthetic effect to delay the post operative pain from the surgery
for as long as possible
--0.5% solution with vasoconstrictor
--toxicity showed by the pKa is very basic
--Onset time is longer than other drugs b/c most of the radicals (about 80%) bind to sodium
channel proteins effectively
--most toxic local anesthetic drug
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37. Drugs used in dental anesthesia
Prilocaine (Citanest®)
--Identical pKa and same conc. with lidocaine
--Almost same duration as lidocaine
--Less toxic in higher doses than lidocaine b/c small vasodilatory activity
Articaine (Septocaine®)
--newest local anesthetic drug approved by FDA in 2000
--Same pKa and toxicity as lidocaine, but its half life is less than about ¼ of lidocaine
--Used with vasoconstrictor.
--Enters blood barrier smoothly
--The drug is widely used in most nations today
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39. The Other Drugs in a Local Anesthesia Carpule
The dentist will make a solution for the local anesthesia to be
administered prior to the surgery. Some of the other drugs in the
solution may contain an antioxidant to prevent a breakdown of the
vasoconstrictor, sodium hydroxide to adjust the acidity of the anesthetic
so it works more effectively, sodium chloride, to help the solution enter
the bloodstream more effectively and sometimes epinephrine which
also works to narrow blood vessels to help the anesthetic last longer.
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40. Vasoconstrictors
Vasoconstrictors, such as epinephrine and norepinephrine, are commonly
contained in local anesthetics to decrease systemic toxicity and prolong
the duration of action by retarding anesthetic absorption.
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41. Clinical Consideration
These catecholamines have varying degrees of α and β adrenergic
effects, resulting in cardiac and hemodynamic changes
In cardiac patients, the administration of low concentration of epinephrine
might be necessary according to the degree of severity of the disease.
These doesn`t mean the use of epinephrine free local anesthetics but to
make sure that it is not directly administrated in the blood.
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42. How is it administered?
There are two local anesthesia injections a dentist will use. There is
something called an infiltration injection which numbs a small area and
there is a block injection which numbs a larger region. All of the
injections are done in the interior of the mouth.
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43. Side Effects:
One possible side effect is hematoma, which is a blood filled swelling
that can form when the needle accidentally punctures a blood vessel.
You may also feel numbness outside the targeted area and this may
cause drooping in your eyelid or lips. The effects of drooping will
disappear when the anesthesia wears off. Allergic reactions are also
rare; however it is important to tell your doctor about any medication
you are taking.
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44. Side Effects:
Some of the side effects include a numb mouth, which is of course
the point of the anesthetic in the first place but other effects include
dizziness and the feeling that you have a fat or swollen lip. Other
than that, side effects are very rare, which is part of the reason the
local anesthetic is so popular in dental procedures.
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