Clinical Actions of Specific Agents

Local Anesthetic Armamentarium In North America:

1) Articaine (Septocaine) gold2) Bupivacaine (Marcaine) blue3) Lidocaine (Xylocaine) red4) Mepivacaine (Carbocaine) (Polocaine) brown5) 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Procaine and propoxycaine were withdrawn from the United States market in January 1996

Etidocaine was withdrawn from United States use in 2002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 HCl4% + epinephrine 1:100,000 (intermediate acting)4% + epinephrine 1:200,000 (intermediate acting)

• Bupivacaine HCl0.5% + epinephrine 1:200,000 (long acting)

• Lidocaine HCl2% + epinephrine 1:50,000 (intermediate acting)

2% + epinephrine 1:100,000 (intermediate acting)

• Mepivacaine HCl3% Plain (short acting)

2% + levonordefrin 1:20,000

• Prilocaine HCl4% 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 hyper-

responders, 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 AgentsLocal Anesthetic mg/lb MRD (mg)

MalamedArticainewith vasoconstrictor 3.2 mg/lb 500 mg same

Bupivacainewith vasoconstrictor 0.6 mg/lb 90 mg same

Lidocaineno vasoconstrictor 2.0 mg/lb 300 mg samewith vasoconstrictor 3.0 mg/lb 500 mg 2.0/300 mg

Mepivacaineno vasoconstrictor 3.0 mg/lb 400 mg 2.0/300

mgwith vasoconstrictor 3.0 mg/lb 400 mg 2.0/300 mg

Prilocaineno vasoconstrictor 2.7 mg/lb 400 mg samewith vasoconstrictor 2.7 mg/lb 400 mg 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% 20 36

3% 30 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 Articainehas 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