PHARMACOLOGY OF LOCAL

ANESTHETICS
DR. DANIEL R. FARNACIO
OBJECTIVE

• The presence of a local anesthetic in the circulatory system means

that the drug will be transported to every part of the body. Local
anesthetics have the ability to alter the functioning of some of these
cells. In this chapter, the actions of local anesthetics, other than their
ability to block conduction in nerve axons of the peripheral nervous
system, are reviewed.
• LA differs from most other drugs in one important manner.

• The presence of a LA in the circulatory system means that the drug

will be transported to every part of the body.
Pharmacokinetics of LA
• Uptake
• Distribution
• Biotransformation
• Excretion
Uptake
• When injected into soF Gssue, LA exerts a pharmacological acGon on
blood vessels in the area.
• All LA have a degree of vasoacGvity, most producing dilataGon of the
vascular bed into which they are deposited.
• Procaine (Ester LA) is the most potent vasodilator drug.
• Cocaine is the only LA producing vasoconstricGon.
A significant clinical effect of vasodilata2on is an
• increase in the rate of absorp2on of LA into the
blood.
• Decreasing in the dura2on, quality, and depth of
pain control while increasing the possibility of
toxic overdose.
Uptake
• Oral Route. With the exception of cocaine, LA are absorbed poorly
from GIT.
• Topical Route (Tracheal mucosa, Pharyngeal mucosa, esophageal or
bladder mucosa) (Skin)
• Injection. The rate of uptake is related to the vascularity of the
injection site and the vaso-activity of the drug. (IV, IM,SC).
Distribu(on
• Once absorbed into the blood, LA are distributed throughout
out the body to all the tissues.
• Highly perfused organs such as brain, head, liver, kidneys,
lungs, and spleen initially have higher blood levels of the
anesthetic than do less highly perfused organs.
The blood level of LA is influenced by:
• 1. Rate of absorp=on
• 2. Rate of distribu=on of the drug from the vascular
compartment to the =ssues
• 3. Elimina=on of the drug through metabolic or excretory
pathways.

• Elimina=on half life: is the =me necessary for 50% reduc=on

in the blood level.
Metabolism (Biotransforma1on)
• Ester LA Hydrolyzed in the plasma by the enzyme
pseudocholinesterase.

• Amide LA The primary site of biotransforma=on of amide LA

is the liver therefore liver func=on and hepa=c perfusion
influence the rate of biotransforma=on.
Excretion
• The kidneys are the primary excretory organ for both the local
anesthetic and its metabolites.

• Esters appear in only very small concentrations as the parent

compound in the urine.
Systemic ac1on of LA
• CNS
• CVS
• Respiratory
• System Local tissue toxicity
CNS I-Anticonvulsant Properties:
• Procaine, mepivacaine, and lidocaine have been used IV to terminate
or decrease the duraGon of both grand mal, and peGte mal seizures.
• The anGconvulsive blood level of lidocaine is 0.5 to 4µg/ml.
• EpilepGc paGents possess hyperexcitable corGcal neurons at a site
with in the brain. LA has a depressant acGon on CNS, raise the seizure
threshold by decreasing the excitability of these neurons.
II- Pre-convulsive SIGNS AND SYMPTOMS:
• The iniGal SS of overdose are CNS in origin.
• With lidocaine, this second phase is observed at a level between 4.5
and 7µg/ml in the average normal healthy paGent.
• The iniGal clinical SS of CNS toxicity are usually excitatory in nature.
Slurred speech, Shivering, Muscular twitching, Tremors of muscles of
the face, Visual disturbance, Dizziness, Numbness of the tongue and
circum oral region, warm flushed feeling of skin.
III- Convulsive Phase:
• Further elevation of the local anesthetic blood level
produces clinical SS consistent with a generalized tonic
– clonic convulsive episode.
• The duration of seizure activity is related to the LA
blood level and inversely related to Pco2 level
CVS
• LA has a direct depressant action on the myocardium. LA decrease
electrical excitability of the myocardium, decrease conduction rate,
and the force of contraction.
• The therapeutic blood level of lidocaine for antidysrhythmic action
range from 1.8 to 6µg/ml.
• SS of LA overdose will be noted if the blood level rises beyond 6µg/ml
of blood.
• All LA except cocaine produce a peripheral vasodilatation, through
relaxation of the smooth muscle in the wall of the blood vessels.
Respiratory System
• At non-overdose level, they have a direct relaxant acGon on bronchial
smooth muscle, where as at overdose levels they may produce
respiratory arrest as a result of generalized CNS depression.
Local Kssue Toxicity
• Skeletal muscle appears to be more sensiGve to the local irritant
properGes of LA than other Gssues.

• Longer acGng LA produce more localized skeletal muscle damage

than shorter acGng drugs.
Amides
• Lidocaine
• Mepivacaine
• Prilocaine
• Bupivacine
Esters
• Procaine
• Cocaine
• Benzocaine
• Tetracaine
Lidocaine
• Concentra=on - 2%
• Potency - 2X Procaine
• Toxicity - 2X Procaine
• Metabolized - Liver
• Excreted - Kidney
Lidocaine
• Time to onset 2-3 mins
• Half life 90 mins
• Max rec dose
(Malamed) 4.4 mg/kg (2mg/lbs)
(manufac.)
w/o epi 4.4 mg/kg ( 2mg/lbs)
with epi 6.6 mg/kg (3 mg/lb)
Lidocaine
• Maximum safe dose - 2% with 1:100,000epi Malamed - 300 mg or 8
carpules
• manufac. - 500 mg or 13.5 carpules
Mepivacaine
• Concentration - 2% or 3%
• Potency - 2X Procaine
• Toxicity - 1.5-2X Procaine
• Metabolized - Liver
• Excreted - Kidney
Mepivacine
• Time to onset 1.5-2 mins
• Half life
• Max rec dose 1.9 hrs
(Malamed) 4.4 mg/kg (2 mg/lb)
(manufac.) 6.6 mg/kg (3 mg/lb)
Mepivacaine
• Maximum safe dose - 3% w/o vasoconstrictor
Malamed - 300 mg or 5.5 carpules
manufac. - 400 mg or 8 carpules
Mepivacaine
• Maximum safe dose - 2% with constrictor

Malamed - 300 mg or 8 carpules

manufac. - 400 mg or 11 carpules
Bupivacaine
• Concentration - 0.5%
• Potency - 8X Procaine (4X Lidocaine)
• Toxicity - 8X Procaine (4X Lidocaine)
• Metabolized - Liver
• Excreted - Kidney
Bupivacaine
• Time to onset 6-10 mins
• Half life 2.7 hrs
• Max rec dose 1.3 mg/kg (0.6 mg/lb)
• Max safe dose 90 mg or 10 carpules
Procaine
• ConcentraGon - 2-4%
• Potency - 1
• Toxicity - 1
• Metabolized - hydrolyzed in plasma by pseudocholinesterase to PABA
• Excreted - Kidney No longer available in dental carpules
Procaine
• Time to onset 6-10 mins
• Half life Duration (with v/c) 0.1 hr pulp - 30-60 mins tissue
• Max rec dose - 2-3 hrs 6.6 mg/kg (3 mg/lb)
• Max safe dose 400 mg
Procaine
• Strong vasodilatation - very short duration of pulpal anesthesia
• High incidence of allergic reactions
• Drug of choice for Tx of inadvertent intraarterial injection (relieves
pain and spasm)
• Consider for Amide allergic patient
What is the value of adding VC to the LA
solution?
Vasoconstrictors
• Constrict blood vessels
• Decrease blood flow
• Decrease the blood level of the drug
• Increase the concentra=on of drug at the site
• Decrease bleeding at site
Factors in Selec1on of Vasoconstrictor
• Length of the dental procedure
• The need for hemostasis during and following procedure
• The medical status of the patient
References
• Meechan, et al., Hand book of local anaesthesia, 1998. SF Malamed:
Pain and anxiety control for the conscious dental paGent, 1997.