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Fourth Edition - 2016

on the pKa of the drug and the pH of the solution. At the


usual solution pH of 6.0 or lower, most local anesthetics
are almost completely in the ionized form.

That portion which is ionized has difficulty penetrating


the nerve and will not be effective. Only the nonionized
Local anesthetics (LAs) mechanism of action: free-base form of the drug can readily penetrate tissue
They reversibly block the specific sodium channels membranes. The lower the pKa of the drug and the
thereby blocking the sodium uptake. This decreases the higher the pH of the solution or injected tissues, the
nerve excitability below a critical level and interfere with more free-base will be available (more effective LA).
the propagation of action potential in nerve fibers.
 Remember: Hydrolysis of local anesthetics salt is
 Remember: Local anesthetics are able to block every
facilitated by a tissue pH above 7.
type of nerve tissue; however, certain nerve fibers
o Alkalinization of a LA solution speeds the
are more susceptible. For example in a mixed nerve,
onset of its action. increases its clinical
sensory fibers are more susceptible than motor
effectiveness,and makes its injection more
fibers. In general, following anesthetic injection,
comfortable.
sensation will be lost in the following order:
 At physiologic pH of 7.4 approximately 5-20%
pain→ cold → warm→ touch→ deep pressure → motor
of the local anesthetic is in free-base form which
 Small, nonmyeinated-nerve fibers, which conduct is enough to penetrate and cause anesthesia.
pain and temperature sensations, are affected first,  If infection (like a dental abscess) or
followed by touch, proprioception (pressure), and inflammation is present, the pH of the tissues
skeletal muscle tone (motor) which are larger, may be acidic (low pH) and there is a
myelinated nerve fibers. significant reduction in the concentration of the
free-base form. In this situation, the local
anesthetic may not be effective because the
Pharmacology:
acidity of infected tissue interferes with the
All LAs are marketed as water-soluble acid salts and are
action of LA solution.
comprised of a lipophilic aromatic ring linked to a
hydrophilic amino group.
In solution an equilibrium is established between the
ionized and the nonionized forms of the LA. So the
penetration of a local anesthetic into nerve tissue is a Agents: Lidocaine (Xylocaine®), Articaine,
function of the lipid solubility of the unionized form. Bupivacaine, Etidocaine, Mepivacaine, Prilocaine,
Ropivacaine, Dibucaine.
The proportion of the drug in the ionized form depends
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PHARMACOLOGY FOR CANADIAN DENTISTS (BY Dr Mehdi Adibrad)

Metabolism: by the hepatic microsomal enzyme system Safest local anesthetic to use in pediatrics is 2%
in liver and excreted primarily in the urine. lidocaine with 1:100,000 epinephrine.
 The most abundant urinary metabolite of For pregnant women, lidocaine and prilocaine have
lidocaine is 4-hydroxyxylidine. the best FDA ranking. Lidocaine may be preferable
 Metabolism mechanism of amide type LAs: because it has a low-concentration formulation,
Dealkylation, Hydrolysis and Hydroxylation. which makes it easier to minimize the total dose. For
 Hepatic function does not affect the topical preparations, lidocaine also has the safest
duration of action of local anesthesia, rating.
which is determined by redistribution and
not biotransformation. Therefore, a patient
with liver disease needs the standard
amount of local anesthetic at each site.
 When treating a patient with significant
liver disease, it is prudent to treat one
quadrant at a time, thereby minimizing
total dose. Use of an ester may not offer
any advantage, because
pseudocholinesterase is also synthesized in
the liver.

Note: Lidocaine (Xylocaine®) is the most


commonly used amid-type LA in dentistry. It is
also available in topical and mouth wash forms.
At higher levels it has antiarrhythmic and
anticonvulsant properties.  There are no significant differences in the response
Note: Articaine 4% is an amide-type local to local anesthetics between younger and older
anesthetic, but it has an ester group attached to its
molecule. Therefore, it is the only amide which is adults. Therefore, the doses required for each block
metabolized in the bloodstream by plasma are the same regardless of patient age. Nonetheless,
cholinesterase and not the liver. it is prudent to stay well below the maximum
Note: Prilocaine is less potent and causes less recommended doses, as elderly patients often have
vasodilation than lidocaine. It is about one-half as some compromise in liver function. Responses to
toxic as Lidocaine, but since methemoglobinemia vasoconstrictors should not be considered
is a possible reaction, Prilocaine should not be significantly different in elderly patients, but some
used for patients with hypoxic conditions like
anemia. degree of cardiovascular compromise can be
Note: Articaine 4% and prilocaine 4% are expected, even without an overt history of heart
reported as more likely than other anaesthetics to disease. Therefore, reducing the dose of epinephrine
be associated with paraesthesia. It is more may be prudent.
common with lingual or mandibular block
injections.
Note: EMLA Cream is a mixture of lidocaine
2.5% and prilocaine 2.5%.

 Bupivacaine has the longest duration of action of


any dental local anesthetic presently available. It
should be avoided in children.

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PHARMACOLOGY FOR CANADIAN DENTISTS (BY Dr Mehdi Adibrad)

Maximum recommendation doses (according


to Canadian guidelines):

Duration of Action of AMID-TYPE LAs:

Important: A dental carpule contaios 1.8 ml solution. formed. If a patient has an allergy to PABA, all
ester-type LA agents are contraindicated.
 Note: 1.8 ml of 2% solution of Lidocaine with  PABA can decrease the effectiveness of
1:100,000 epinephrine contains 36 mg of
sulfonamides (antibiotics).
Lidocaine and 0.018 mg epinephrine.
Important: All local anesthetics except cocaine are
vasodilators; however, mepivacaine has less of a
vasodilator effect compared to the others and,
Agents: Procaine (Novocaine®), Propoxycaine, therefore, is the drug chosen when a vasoconstrictor
Benzocaine, Tetracaine, Cocaine. is not used with the local anesthetic.
 Note: Ester-type LAs are no longer available as  Cocaine causes significant euphoria (due to its
dental anesthetic injectable preparations because of
blockade of reuptake of catecholamines and
their relatively high incidence of allergy. They are
mainly available as topical anesthetics (like dopamine in the brain), and its abuse can lead to a
benzocaine). physical dependence. Cocaine increases the
Metabolism: by the plasma pseudocholinesterase (a pressor activity of other sympathomimetic amines
plasma enzyme). and can increase the risk of developing cardiac
o When procaine is metabolized, a highly allergic arrhythmias and hypertension.
compound called para aminobenzoic acid (PABA) is  Avoid epinephrine altogether in patients who
have ingested cocaine within the previous 24

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PHARMACOLOGY FOR CANADIAN DENTISTS (BY Dr Mehdi Adibrad)

hours, as there is increased risk of cardiac Light headedness, Nervousness, Drowsiness,


dysrhythmias and increased blood pressure Numbness,….
(absolute contraindication). 2. Moderate to High Overdose Levels: Tonic–clonic
seizure activity followed by: Generalized CNS
 Note: Phentolamine mesylate (Oraverse) is an depression, depressed blood pressure& heart rate and
alpha 1 adrenergic receptor blocker and causes respiratory depression.
vasodilation. It is administered as a submucosal
 Note: The cardiovascular collapse caused by
injection after a dental procedure to reverse the
LA toxicity is the result of myocardial
local anesthetics effect  50% decrease in the
time for normal sensation to return. depression.
 Note: It is possible that the “excitatory” phase
 Note: Dyclonine hydrochloride is an unusual of the overdose reaction may be extremely brief
anesthetic agent that can be used for topical or may not occur at all, in which case the first
anesthesia usually in the form of a mouth wash. clinical manifestation of overdose may be
drowsiness progressing to unconsciousness and
respiratory arrest. This appears to be more
LA side effects: common with lidocaine than with other local
anesthetics.
Toxicity:  Note: Opioids can increase the systemic toxicity
The toxicity of local anesthetics is a function of systemic of local anesthetics.
absorption. The toxic reaction is due to high blood level  Note: Esters will show greater toxicity in
of the anesthetic agent. Excessive blood levels of the patients with a hereditary deficiency of plasma
drug may be due to repeated injections or could result esterases.
from a single inadvertent intravascular administration.
 Causes: overdose due to injecting too much LA
(most common cause), Inadvertent intravascular
injection of LA.
 Note: The high-concentration solutions, namely
prilocaine (4%) and articaine (4%), will reach
toxic levels with fewer injections than is the
case for the other drugs.
 Note: LA toxicity is more likely to occur in
children and may appear as a seizure.
 Note: “Aspiration” prior to LA injection
reduces the risk of IV administration. In cases
of positive aspiration, the position of needle in
the vein lumen can be confirmed by the color
of blood upon aspiration.
 Remember: Local anesthetics exert a depressant
effect on all excitable membranes including
CNS. But the toxicity symptoms are excitatory at  Allergy:
lower doses which change into depression phase at Allergic reactions are more prevalent with the ester-type
higher doses. rather than the amide-type anesthetics.
Signs and Symptoms:  Note: An allergy to one ester rules out use of
1. Minimal to Moderate Overdose Levels: Excitement
another ester, as the allergenic component is the
(first sign), Talkativeness, Apprehension, Slurred
breakdown product paraaminobenzoic acid, and
speech, Vomiting (nausea), Elevated blood pressure
metabolism of all esters yields this compound. In
and heart rate, elevated respiration rate, tremors,
contrast, an allergy to one amide does not rule out

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PHARMACOLOGY FOR CANADIAN DENTISTS (BY Dr Mehdi Adibrad)

use of another amide. Allergy to epinephrine is  Clinical signs: cyanosis, decreased pulse
impossible. oximetry, “chocolate-colored”blood
 Treatment: IV methylene blue (1–2 mg/kg of
 “Sodium metabisulfite” prevents the oxidation of 1% solution over 5 minutes).
the epinephrine in dental cartridges. It may cause
allergy in patients with a history of asthma and
hypersensitivity to sulfites. It may be best to avoid a Paresthesia:
vasoconstrictor if there is a true documented allergy Articaine and prilocaine were reported as more
to sulfites, as metabisulfite is added as an likely than other anesthetics to be associated
antioxidant whenever vasoconstrictor is present. with paresthesia. Such reactions have most
Vasoconstrictor can be used in patients with an commonly affected the lingual nerve.
allergy to the sulfonamide antibacterials, commonly
called sulfa, as there is no cross-allergenicity with
sulfites.

 Note: Preparations without vasoconstrictor such as


mepivacaine 3% and Perilocaine 4% do not
contain bisulfites.
 Note: Methylparaben, which was used as a
bacteriostatic preservative in vials, can also cause
allergies. It is not used in cartridges anymore.
 Signs and symptoms: Dermatitis, Urticaria, Fever,
Angioedema, Depression of blood-forming organs,
Hypotension, Anaphylaxis.
 Note: In case of allergy to both amides and ester
type LAs, a H1 antihistamine agent injection like
Diphenhydramine can be used for local
anesthesia.

 Methemoglobinemia:
Hemoglobin is oxidized to methemoglobin which cannot
bind and carry oxygen. It is caused by excessive doses of
benzocaine, prilocaine, or rarely lidocaine.

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PHARMACOLOGY FOR CANADIAN DENTISTS (BY Dr Mehdi Adibrad)

levonordefrin is contraindicated in individuals


taking tricyclic antidepressants.

Functions:
 prolongs the duration of action and increases its
depth,
 increases depth of anesthesia,
 permits smaller volumes of LA to be administered,
 reduces risk of systemic toxicity,
 reduces the rate of vascular absorption,
 provides a hemostatic effect.

 Factors that affect the selection of a vasoconstrictor


for a LA:
o the length of procedure,
o the need for hemostasis,
o patient medical condition.

 Note: Vasoconstriction is more important for


infiltration techniques in vascular sites than it is for
mandibular blocks.
 Important: Minimizing the likelihood of systemic
effects of vasoconstrictors is another reason why
aspiration before every injection is so important.

 Remember: Vasoconstriction is due to


epinephrine’s stimulation of α1 receptors in
mucous membranes. However, it also stimulates
the ß1receptor in the heart, increasing heart rate,  Note: Epinephrine should also be avoided in
strength of contraction and myocardial oxygen patients with uncontrolled hyperthyroidism.
consumption, and the ß2 receptors, vasodilating
blood vessels in the skeletal muscle.
 Note: Contrary to the information in certain drug
monographs, epinephrine can be given to patients
receiving monoamine oxidase inhibitors.
 Note: Levonordefrine is present in cartridges of
mepivacaine 2%. It is available as a 1:20,000
solution and should be considered equivalent to
1:100,000 epinephrine. The administration of

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PHARMACOLOGY FOR CANADIAN DENTISTS (BY Dr Mehdi Adibrad)

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