LOCAL ANESTHETICS IN DENTISTRY

Local Anesthetics– ATC - N01B

• a group of chemically similar agents
• Block sensory transmission by blockade of the sodium channels
• from a limited area of the body to the CNS
• administered locally
• topically (surface) or by injection - target area,
– the anesthetic effect can be restricted to a localized area, eg, the conea
• Effect terminated by absorption to systemic circulation
– systemic adverse effects
• Many drugs classified in other groups, have significant local
anesthetic effects
– eg, antihistamines and beta-blockers,.
 Chemistry
• esters vs amides
• of simple benzene derivatives
• weak bases
– all carry at least one amine function
– Administered as hydrochloride salts
• the degree of ionization – pKa vs pH
– pKa – pH = log proton/unprot (B + H+ = BH+)
– pKa of most local anesthetics is between 8.0 and 9.0
– Variable effect in inflammed tissue – low pH
– Tachyphylaxis possible – large dose
– Usually after epidural adminsitration
Cocain Procain Lidocain

Articain Bupivacain Mepivacain

 Mechanism of Action
• block voltage-dependent sodium channels
• reduce the influx of sodium ions
– prevents depolarization - block conduction of the action potential.
• Reach receptors from the cytoplasm or through the membrane.
– the drug molecule must cross the lipid membrane
– the more lipid-soluble (nonionized, uncharged)
– form reaches effective intracellular concentrations more rapidly than does the
ionized form.
• once inside the axon, the ionized (charged) form of the drug is the
more effective blocking entity.
– Thus, both the nonionized and the ionized forms are important
– the first in reaching the receptor site and the second in causing the
effect.
Binding of local anesthetic to receptor

• The affinity of the receptor site within the sodium channel

for the LA is a function of the state of the channel
• drugs binds to open and inactivated channels, therefore for
those with higher activity/firing
• use dependence - rapidly firing fibers are usually blocked
before slowly firing fibers.
Factors affecting onset and duration of
action of local anesthetics
• pH of tissue/pKa of drug
• Lipid solubility of drug
• Concentration of drug – adrenaline
– High perfusion of area limits effect
• Nerve morphology
– Time of diffusion from needle tip to nerve
– Time of diffusion away from nerve
 Effects
• Nerves
• Differential sensitivity of various types of nerve fibers to LA - several
factors:
– fiber diameter
• smaller fibers are blocked more easily than larger,
• myelination - myelinated fibers are blocked more easily than
unmyelinated ones,
– physiologic firing rate
• Use dependence - activated pain fibers fire rapidly - selectively
blocked
– anatomic location
• fibers located in the periphery of a thick nerve bundle are blocked
sooner than those in the core - exposed earlier to higher
concentrations of the anesthetic - sensory.
• Other tissues
– class I antiarrhythmic agents.
• Most local anesthetics also - weak blocking effects on skeletal muscle
neuromuscular transmission - no clinical application
– The mood elevation induced by cocaine – CNS effect by ↑
dopamine
 PK
• effect terminated by absorption
– to systemic circulation
• Lipophilic - inactivated by metabolism
– Pseudocholinesterase – esters
• Esters more hydrophilic
– Poor penetration after topical administration
– Liver CYP450 – amides
• Mostly short t1/2 – minutes
Susceptibility to block of types of nerve fibers.*
Function Diamet Myelinatio Conduction Sensitivity
Fiber Type er (mm) n Velocity to Block
(m/s)
Type A
Alpha Proprioception, 12-20 Heavy 70-120 +
motor
Beta Touch, pressure 5-12 Heavy 30-70 ++
Gamma Muscle spindles 3-6 Heavy 15-30 ++
Delta Pain, 2-5 Heavy 12-30 +++
temperature
Type B Preganglionic <3 Light 3-15 ++++
autonomic
Type C
Dorsal root pain 0.4-1.2 None 0.5-2.3 ++++
Sympathetic postganglionic 0.3-1.3 None 0.7-2.3 ++++
*Reproducedfrom Katzung BG (editor): Basic & Clinical Pharmacology, 8th ed. McGraw-Hilf, 2001,
 Clinical Use
– minor surgical procedures – topical, infiltration
• most commonly
– nerve blockade
– spinal anesthesia
– autonomic blockade in ischemic conditions
– Slow epidural infusion
• at low concentrations has been used successfully for postoperative
analgesia
• in the same way as epidural opioid infusion (bupivacain-sufentanyle)
• Repeated epidural injection in anesthetic doses may lead to
tachyphylaxis.
• Interactions
– High concentrations of extracellular K+ may enhance local
anesthetic activity,
– B-blockers potentiate LA action
– elevated extracellular Ca2+ may antagonize it.
– Ca2+ channel blockers potentiate LA
 Adverse effects:
– overdose, accidental iv administration – always aspirate
• CNS effects - seizures
– initially
• manifest as sedation, lightheadedness, slurred speech, sensory
disturbances, restlessness, nystagmus;
– higher blood levels
• may result in tremor, respiratory depression and tonic-clonic
convulsions. Severe convulsions may be followed by coma with
respiratory and cardiovascular depression.
– Diazepam i.v. (or thipental), hyperventilation with oxygen
• Cardiovascular effects – bradycardia/hypotension
– Vasodilators
• With the exception of cocaine - !!! Adrenalin
– Patients with preexisting cardiovascular disease may develop
heart block
• and other disturbances of cardiac electrical function at high plasma
levels of local anesthetics.
• Bupivacaine may produce severe cardiovascular toxicity, including
arrhythmias and hypotension, if given intravenously.
 Other toxic effects
• Prilocaine
– Methemoglobinemia - by metabolite
• Allergic responses
– to local anesthetics are rare (<1%)
– can usually be avoided by using an agent from the amide subclass.
• The ester-type local anesthetics
– are metabolized to products that can cause antibody formation in some
patients.
• Local neurotoxic action
– In high concentrations of LA
– histological damage and permanent impairment of function
 Cocaine
• ester
• block norepinephrine reuptake at sympathetic
neuroeffector junctions
– vasoconstricting actions
• When used as a drug of abuse
– cocaine's cardiovascular toxicity includes severe
hypertension with cerebral hemorrhage, cardiac
arrhythmias, and myocardial infarction.
 POST-ANESTHESIA TRAUMA

• The number one postoperative complication of

local anesthesia in children.
POST-ANESTHESIA TRAUMA

Minor to major. Always painful.

Other Post-Anesthesia Conditions

Blanching due to
vasoconstrictor
Other Post-Anesthesia Conditions

Hematoma due to local anesthesia

 Classification of local anesthetics
• Duration of action:
– short acting (< 60 min)
• procaine
– medium acting (60-120 min):
• lidocaine, mepivacaine, prilocaine, trimecaine, articaine
– long acting(> 120 min):
• bupivacaine, tetracaine, etidocaine, ropivacaine
• Chemical structure
– esters:
• procaine, tetracain, cocaine
– amides:
• lidocain, trimecain, mepivacain, bupivacain, ropivacain,
articain, prilocain, etidocain
Estery
léčivo relativní klinické koncentrace nástup trvání
účinek využití % účinku účinku
prokain 1 I 1 pomalý 30-45 min
S 2
chlorprokain 1 I 1 rychlý středně
E 2 dlouhé
S 2
tetrakain 8 P 0,5-1 rychlý dlouhé
I 0,1-0,12
Bl 0,1-0,2
E 0,25-0,5
S 1

vysvětlivky: klinické využití k anestesii P = povrchové, I = infiltrační, Sv – svodné, Bl-

blokády velkých nervů, E = epidurální, S = subarachnoidální
Amidy
léčivo relativní klinické koncentrace nástup trvání účinku
účinek využití % účinku
artikain 2 I 4 rychlý 60 min
E 2
S 5
lidokain 2 P 2-10 rychlý 60-120 min
I 0,5-1
Bl 1-1,5
E 1-2
S 5
mesokain 2 P 2-10 rychlý 60 min
(trimekain) I 0,5-1
Bl 1-2
E 1-2
S+ ) 2
vysvětlivky: klinické využití k anestesii P = povrchové, I = infiltrační, Sv – svodné, Bl-
blokády velkých nervů, E = epidurální, S = subarachnoidální
léčivo relativní klinické koncentrace nástup trvání účinku
účinek využití % účinku
mepivakain 2 I 0,5-1 poměrně 90-160 min
Bl 1-1,5 rychlý
E 1-2
S 4
bupivakain 8 I 0,125- 0,25 pomalý 4-8-12 hod
Bl 0,25-0,5 (nízké
E 0,25-0,75 koncentrace
S 0,5 kratší)
ropivakain++) 2 I 0,75-1 poměrně 2-6 hod
E 0,2 rychlý
prilokain+++) 2 I 0,5-1 poměrně 90-180 min
Bl 1 rychlý
E 2
etidokain 6 I 0,5 rychlý 4-8 hod
Bl 0,5 –1
E 1

vysvětlivky: klinické využití k anestesii P = povrchové, I = infiltrační, Sv – svodné, Bl-

blokády velkých nervů, E = epidurální, S = subarachnoidální
+) jako přísada, ++) nepoužívat subarachnoidálně +++) nepoužívat v porodnictví (riziko

methemoglobinemie).