Transcript Clinical Actions of Specific Agents

Clinical Actions of
Specific Agents
Local Anesthetic Armamentarium In North America:
1) Articaine (Septocaine)  gold
2) Bupivacaine (Marcaine)  blue
3) Lidocaine (Xylocaine)  red
4) Mepivacaine (Carbocaine) (Polocaine)  brown
5) Prilocaine (Citanest)  black - yellow
Procaine and propoxycaine were withdrawn from the
United States market in January 1996
Etidocaine was withdrawn from United States use in 2002
• Articaine HCl
4% + epinephrine 1:100,000 (intermediate acting)
4% + epinephrine 1:200,000 (intermediate acting)
• Bupivacaine HCl
0.5% + epinephrine 1:200,000 (long acting)
• Lidocaine HCl
2% + epinephrine 1:50,000 (intermediate acting)
2% + epinephrine 1:100,000 (intermediate acting)
• Mepivacaine HCl
3% Plain (short acting)
2% + levonordefrin 1:20,000
• Prilocaine HCl
4% Plain (short acting for infiltration; intermediate acting for block)
4% + epinephrine 1:200,000 (intermediate acting)
Duration of Action
Duration of hard and soft tissue anesthesia is only an approximation; there are
many factors that can prolong or decrease the level of anesthesia:
1) Individual response to the drug
-70% normal, 15% hyper-responders and 15% hypo-responders
2) Accuracy of deposition of the drug
-depositing the solution close to the nerve provides greater duration
3) Status of the tissues at the site of drug administration
-inflammation, infection and pain; vascularity of tissues
4) Anatomical variation
-height of mandibular foramen; width of ramus
-position of the palatal root
5) Type of injection administered
-block anesthesia vs. supraperiosteal injection
“Bell-Shaped Curve”
Individual Responses to a Drug
Maximum Doses of Local
Anesthetic (MRD)
Doses of anesthetic drugs are presented in terms of:
Milligrams of drug per unit of body weight,
either milligrams per kilogram or milligrams
per pound (mg/kg or mg/lb)
Always minimize drug doses and use the smallest clinically effective
dose for all individuals: normal, hyper, hypo-responders
MRDs Of Local Anesthestics
-The American Council on Dental Therapeutics of the ADA and The
United States Pharmacopeial Convention (USP) reviewed the MRDs
for local anesthetics and no longer adjusts them for inclusion of a
vasoconstrictor
-Changes in liver function, plasma protein binding, blood volume and
other important physiological functions influence the manner in which
local anesthetics are distributed and biotransformed in the body
-The half lives of amide local anesthetics are increased in the presence of
decreased liver function or perfusion
-When the MRD is exceeded there is no guarantee that an overdose will
occur, only that there is a greater likelihood of it arising; in hyperresponders, an overdose may occur under the MRD
The maximum calculated drug dose
always should be decreased in medically
compromised, debilitated, or elderly
persons
Common Question: “How do I determine the maximum recommended
dose of each local anesthetic administered in
clinical situations where more than one drug is
necessary?”
Answer: Ensure that the total dose of both local anesthetics not exceed
the lower of the two maximum doses for the individual agents
MRDs for Specific LA Agents
Local Anesthetic
Articaine
with vasoconstrictor
mg/lb
MRD (mg)
Malamed
3.2 mg/lb
500 mg
same
Bupivacaine
with vasoconstrictor
0.6 mg/lb
90 mg
same
Lidocaine
no vasoconstrictor
with vasoconstrictor
2.0 mg/lb
3.0 mg/lb
300 mg
500 mg
same
2.0/300 mg
Mepivacaine
no vasoconstrictor
with vasoconstrictor
3.0 mg/lb
3.0 mg/lb
400 mg
400 mg
2.0/300 mg
2.0/300 mg
Prilocaine
no vasoconstrictor
with vasoconstrictor
2.7 mg/lb
2.7 mg/lb
400 mg
400 mg
same
same
Calculations of Milligrams of Local Anesthetic
Per Dental Cartridge (1.8 ml Cartridge)
Local Anes. % conc. mg/ml
X 1.8 ml = mg/cartridge
Articaine
4%
40
72
Bupivacaine
.5%
5
9
Lidocaine
2%
20
36
Mepivacaine
2%
3%
20
30
36
54
Prilocaine
4%
40
72
2% Lidocaine 1:100,000 epinephrine has a
MRD of 300 mg; that does not mean that
anyone can have up to 300 mg; this number is
based on a patient’s weight, therefore, a 80 lb.
child cannot have 300 mg of 2% Lidocaine
1:100,000 epinephrine
80 lb. X 2.0 mg/lb. = 160 mg MRD
160 mg / 36 mg/ cartridge = 4.4 cartidges
MRD Examples
Patient: 22 year old, healthy, female 110 lbs.
Drug: Lidocaine 2% no vasoconstrictor = 36 mg/cartridge
Maximum Recommended Dose: 110 lbs. x 2.0 mg/lb = 220 mg
Number of Cartridges: 220 mg / 36 mg = 6.1 cartridges maximum
Patient: 6 year old, healthy, male 40 lbs.
Drug: Mepivacaine 3% Plain = 54 mg/cartridge
Maximum Recommended Dose: 40 lbs. x 2.0 mg/lb = 80 mg
Number of Cartridges: 80 mg / 54 mg = 1.5 cartridges maximum
Types of Local
Anesthetics Used
By Dentists In The
United States
Procaine + Propoxycaine
(Novocain)
(discovered in 1904)
Procaine (Ester)
-hydrolyzed rapidly in plasma by plasma
pseudocholinesterase
-excreted more than 2% unchanged in the urine; 90%
as PABA and 8% as diethylaminoethanol
-pKa = 9.1; this is why the onset is very long
-pH of plain solution = 5.0 to 6.5
-pH of vasoconstrictor solution = 3.5 to 5.5
Procaine
-onset of action = 6 to 10 minutes
(very long by amide standards)
-effective dental concentration = 2% to 4%
-half-life = 6 minutes
-topical anesthetic action = none
-produces the greatest vasodilation of all current
local anesthetics
Procaine (Ester)
the first synthetic injectable local anesthetic
proprietary name of Novocain is known around the world
2% procaine plain provides essentially no pulpal anesthesia
2% procaine plain provides 15 to 30 minutes of soft tissue anesthesia
the short duration of action is due to its profound vasodilating effects
its vasodilating properties are used to break arteriospasm
metabolized in the blood by plasma cholinesterases
hepatic dysfunction is not a problem with procaine
MRD = 1000 mg
pKa of 9.1 means slow onset which is why propoxycaine is added
Lidocaine
(Xylocaine)
Lidocaine (Amide) (discovered 1943)
metabolized in the liver by microsomal fixed-function oxidases
byproducts are monoethylglyceine and xylidide
excreted via the kidneys less than 10% unchanged
more vasodilating than Prilocaine or Mepivacaine
pKa = 7.9
pH of plain solution = 6.5
pH of vasoconstrictor solution = 5.0 to 5.5
onset of action = 2 to 3 minutes (rapid)
effective dental concentration = 2%
anesthetic half-life = 90 minutes
-topical anesthetic action = yes; in 5% concentration
-MRD (vasoconstrictor-containing) = 3.2 mg/lb not to exceed 500 mg
-Malamed recommended MRD = 2.0 mg/lb not to exceed 300 mg
-1st amide local anesthetic to be marketed replacing Novocaine
-Lidocaine provides more rapid, more profound anesthesia, longer duration and greater
potency than Procaine (Novocaine)
-Allergy to amide local anesthetics is virtually nonexistent, although possible
-extremely rare allergy is a major advantage of amides over esters
-2% Lidocaine comes in plain, 1:50,000 epinephrine and 1:100,000 epinephrine
-only recommended use of 2% Lidocaine 1:50,000 epinephrine is to
provide hemostasis by injecting volumes directly into surgical site
-the MRD for epinephrine sensitive individuals is 40 micrograms
(.04 mg) per appointment which is equivalent to 2 cartridges of
1:100,000 epinephrine (each cartridge contains .018 mg epinephrine)
-the MRD for healthy individuals is .20 mg epinephrine per appointment
(.018 mg/cartridge with 1:100,000 epinephrine X 11.1 cartridges = .20 mg epinephrine)
-2% Lidocaine with 1:50,000; 1:100,000; 1:200,000; 1:250,000
epinephrine all provide the same depth/duration of soft/hard tissue
anesthesia, however, not the same level of hemostasis
-1:50,000 epinephrine is not dangerous to most patients but can be to
some ASA II and ASA III patients and to the very young and elderly
Mepivacaine
(Carbocaine / Polocaine) (amide)
-metabolized in the liver by microsomal fixed-function oxidases
-hydroxylation and N-Demethylation play roles in the metabolism
-excreted via the kidneys 1% to 16% excreted unchanged
-produces only slight vasodilation (very important)
-produces pulpal anesthesia without a vasoconstrictor of 20 to 40 minutes
-Lidocaine provides 5 minutes of pulpal anesthesia and Procaine 2 minutes of pulpal
anesthesia without a vasoconstrictor
-pKa = 7.6 (faster onset than Lidocaine)
-pH of plain solution = 4.5
-pH of vasoconstrictor solution = 3.0 to 3.5
-onset of action = 1.5 to 2 minutes (very rapid)
-effective dental concentration = 3% without vasoconstrictor
2% with a vasoconstrictor
-anesthetic half-life = 1.9 hours
-MRD = 2.0 mg/lb; not to exceed 300 mg
-the mild vasodilating properties of Mepivacaine provide a longer
duration of anesthesia than most other anesthetics when the drug is
administered without a vasoconstrictor
-Mepivacaine 3% Plain provides 20 to 40 minutes of pulpal anesthesia
and 2 to 3 hours of soft tissue anesthesia
-Mepivacaine 3% Plain is indicated for patients in whom a
vasoconstrictor is contraindicated
-Mepivacaine 3% Plain is the most used local anesthetic for pediatric
patients when the treating doctor is not a pediatric dentist
-true, documented, reproducible allergy to Mepivacaine, an amide
local anesthetic, is virtually nonexistent
-two types of vasoconstrictors are used with Mepivacaine;
1:20,000 levonordefrin and 1:100,000 epinephrine
-*levonordefrin is difficult to find in North America and it does not
provide the intensity of hemostasis as 1:100,000 epinephrine
Why is Mepivacaine used so
often in children?
1) pKa is 7.6 which allows for faster onset
2) Slight vasodilation so longer duration
3) 3% affords stronger anesthetic solution
Prilocaine (Citanest)
Discovered 1953
-Prilocaine is a secondary amine; also called
Citanest
-hydrolyzed straight-forwardly by hepatic
amidases into orthotoluidine and
N-Propylalanine is a major byproduct of
Prilocaine biotransformation
-extremely small amount of Prilocaine is
detected in the urine
-orthotoluidine can induce the formation of
methemoglobin
-methemoglobinemia occurs most often with
Prilocaine
-Prilocaine consistently reduces the blood’s oxygen
carrying capacity enough to produce observable
cyanosis
-Limiting the total Prilocaine dose to 400 mg avoids
this occurrence (4% cartridge = 72 mg / cartridge)
(400 mg / 72 mg = 5.5 cartridges maximum)
-methemoglobin levels less than 20% do not produce clinical
symptoms of cyanosis, i.e., blue lips and nail beds, respiratory distress
-methemoglobinemia can be reversed w/in 15 minutes by
administering 1 to 2 mg/kg body weight of 1% methylene blue IV
for 5 minutes
-Prilocaine undergoes biotransformation more rapidly and completely
than Lidocaine, taking place in the liver, kidney and lung
-plasma levels of Prilocaine decrease more rapidly than Lidocaine due
to the massive biotransformation thus it is considered less toxic than
other more potent amides
-Prilocaine CNS toxicity is more brief and less severe than Lidocaine
toxicity
-Prilocaine is excreted via the kidneys more rapidly than other amides
-Prilocaine causes vasodilation; albeit less than Lidocaine
-pKa = 7.9 (same as Lidocaine)
-pH of plain solution = 4.5
-pH of vasoconstrictor containing solution = 3.0 to 4.0
-onset of action = 2 to 4 minutes (slightly slower than Lidocaine)
-effective dental concentration = 4%
-half-life = 1.6 hours
-topical anesthetic activity = none (except EMLA- prilocaine + lidocaine)
-MRD = 2.7 mg/lb; 400 mg total
-Prilocaine Plain is able to provide anesthesia that is equal in duration
to Lidocaine with a vasoconstrictor (nerve block)
-Prilocaine Plain provides 10 to 15 minutes of pulpal anesthesia and
1.5 to 2 hours soft tissue anesthesia when given as supraperiosteal
-*Prilocaine Plain provides 60 minutes of pulpal anesthesia and 2 to 4
hours soft tissue anesthesia when given as regional nerve block
-epinephrine sensitive patients requiring prolonged pulpal anesthesia
(greater than 60 minutes) should receive Prilocaine Plain or
Prilocaine 1:200,000 epinephrine (.09 mg epinephrine/cartridge)
-rapid biotransformation makes Prilocaine a relatively safe amide
Prilocaine is relatively contraindicated in patients with
idiopathic or congenital methemoglobinemia, sickle
cell anemia, anemias and hypoxias
Articaine (Septocaine)
Discovered 1969
-1.5 times more potent than Lidocaine
-Articaine is the only amide that contains a thiophene group
-Articaine is the only amide that contains an ester group
-Articaine biotransformation occurs in the plasma and liver
degradation of Articaine by hydrolysis of the
carboxylic acid ester groups to give free carboxylic
acid
excretion via the kidneys with 5% to 10% unchanged
Articaine has vasodilating effects equal to that of
Lidocaine
pKa = 7.8; faster onset than Lidocaine
pH of plain solution = not available
-pH of vasoconstricting solution = 4.4 to 5.2
-onset of action = 1 to 3 minutes
-effective dental concentration = 4%
-Half-life = .5 hours
-topical anesthetic action = none
-MRD = 3.2 mg/lb; 500 mg total
(72 mg per 4% cartridge / 500 = 6.9 cartridges maximum)
-Articaine is becoming the most popular amide local
anesthetic in countries other than the United States
-Articaine holds 26% of the United States amide
local anesthetic sales
-reports of parasthesia have become frequent in the
United States
-Articaine and Prilocaine have been associated with reports of
parasthesia; they are the only amides with 4% concentrations
-no cases of methemoglobinemia have been reported when Articaine
has been used in the normal course of dental anesthesia
-use in children under 4 years of age is not recommended until further
data is analyzed about its safety
“minimum contents of each 1.7 ml” which is printed on each
cartridge of Articaine is there only to show that local anesthetic
cartridges are filled on a conveyor belt by a machine and cannot
guarantee that there is 1.8 ml in each cartridge; consider all these
cartridges to contain 1.8 ml not 1.7 ml as written on the cartridge by
the manufacturer
Bupivacaine (Marcaine)
Discovered 1957
-potency = 4 times that of Lidocaine, Mepivacaine
or Prilocaine
-toxicity = less than four times that of Lidocaine,
Mepivacaine, or Prilocaine
-metabolized in the liver by amidases
-excretion via the kidney; 16% unchanged in urine
-great vasodilating effects; greater than Lidocaine,
Mepivacaine and Prilocaine
-pKa = 8.1 (causes longer onset of action)
-pH of plain solution = 4.5 to 6.0
-pH of vasoconstrictor containing solution =
3.0 to 4.5
-onset of action = 6 to 10 minutes
(much longer than other amides)
-effective dental concentration = 0.5%
-half-life = 2.7 hours
-topical anesthetic action = none
-MRD = 0.6 mg/lb; 90 mg total
(9 mg per .5% cartridge / 90 = 10 cartridges maximum)
2 Utilizations of Bupivacaine in Dentistry:
1) lengthy dental procedure where pulpal anesthesia is
necessary in excess of 90 minutes
2) management of post-operative pain (post-surgical)
-post-operative need for narcotics lessened when you use
Bupivacaine; rarely used in children or mentally
handicapped
Topical Anesthetics
-topically applied local anesthetic is an important part of atraumatic
needle penetration in the oral mucosa; numbs 2 to 3 mm deep
-topical anesthetic concentration is greater than injectable local
concentration
-higher concentrations facilitate diffusion through mucous membranes
-topical anesthetics do not contain vasoconstrictors so absorption into
the blood stream could be quite rapid
-do not inject topical anesthetics
-Examples: Benzocaine, Butamben, Tetracaine HCl, Cocaine,
Dyclonine HCl, and Lidocaine (5% concentration)
-topical anesthetic gel must remain on tissue for at least 1 minute
Eutectic Mixture of Local Anesthetics (EMLA)
-composed of Lidocaine 2.5% and Prilocaine 2.5%
-cream is an emulsion in which the oil phase is a eutectic mixture of
Lidocaine and Prilocaine in a ratio of 1:1
-designed to have topical powers on intact skin (venipuncture)
-EMLA must be applied 1 hour before the procedure
-patients with a history of methemoglobinemia are contraindicated
-EMLA has eliminated use of a needle in some pediatric procedures
-promising for the future of topical pain resolution in all facets of
medicine and dentistry
DentiPatch (Noven)
2.5% Lidocaine, 2.5% Prilocaine
Consider these points when selecting an anesthetic:
1) Length of the procedure; amount of time pain
control is necessary
2) The need for post-treatment pain control
3) The need for hemostasis
4) Contraindications of the local anesthetic
Long appointment: .5% Bupivacaine
Intermediate appointment: 2% Lidocaine 1:100,000 epinephrine
Short appointment: 3% Mepivacaine or 4% Prilocaine
Hemostasis recommended: 1:50,000 epinephrine
(only used for hemostasis)
Absolute contraindication: true, documented, reproducible allergy
*Short, intermediate and long-action amide local + topical is needed
for every dental practice