This document summarizes the pharmacokinetics of local anesthetics. It discusses how local anesthetics are absorbed, distributed, metabolized and eliminated by the body. It also describes the mechanisms of action of local anesthetics on the central nervous system, cardiovascular system and other body tissues. Potential side effects from overdose or interactions with other drugs are also outlined.

1. Of
Local Anesthetics
Based on Text- Local Anesthesia for Dental Professionals
1st ed. Dr. StanleyMalamed 2nd ed. Bassett, DiMarco, Naughton
Local Anesthesia for Dental Professionals

2. Pharmacokinetics

3. Most injectable medications enter circulatory system
to attain therapeutic levels
LA – when redistributed by circulatory system - their action is terminated

4.  All LA possess a degree
of vasoactivity
 Most cause vasodilation
 Some may produce
vasoconstriction
 Drug action and effect is
concentration dependent

5.  Potent vasodilation drugs
 Procaine is the most potent
 Is used to enhance
circulation
 with compromised blood
flows
 Enhances the
redistribution and limits
effect / duration

7. Cocaine
 Initially produces
vasodilation
 Followed by intense and
prolonged
vasoconstriction
 Produced by inhibition of
uptake of norepinephrine

9.  Cocaine is the only LA that is absorbed well by GI
 Most LA (amides) enter the hepatic circulation
 72% is biotransformed and inactivated

10. Topical Route
 Absorbed from mucous
membranes at differing
rates
 Trachea
 – almost as rapid as IV
 Pharyngeal
 – slower
 Oral
 – slow to moderate

11. Injection
 Rate of absorption
following parenteral
injection
 Is related to
 The Vascularity of area
 Vasoactivity of the drug

12.  IV administration of LA
provides rapid elevation of
blood levels
 Used for ACLS treating
ventricular arrythmias
 Rapid administration
 Induces high LA blood
levels
 Can induce serious toxic
reactions
 Absorbed into CNS

13.  Lidocaine should be used
with caution due to
negative cardiovascular
effects which include
 hypotension,
bradycardia,
arrhythmias, and/or
cardiac arrest. Some of
these side effects may be
due to hypoxemia
secondary to respiratory
depression.
Lidocaine 2% @ 1.8 ml = 36 mg lido.

14. Distribution
 CV system distributes
thru body
 Highly perfused organs
 Brain
 Liver
 Kidneys
 Lungs
 Spleen
 Skeletal muscle
 Largest mass of tissue in
body
 Will contain the
greatest % of LA due to
mass

15.  Plasma concentration of LA in each organ
 bears significantly on toxicity of drug
 Affected by
 Rate of absorption
 into CV system
 Rate of distribution
 from the vascular compartment to tissues
 Rate of elimination of drug
 thru metabolic or excretory pathways

17.  Elimination half – life
 Rate at which a LA is removed from blood
 Time necessary for 50% reduction in plasma
concentration
 One half life 50%
 Two half lives 75%
 Three half-lives 87%

19.  ALL local anesthetics
 Cross the blood brain
barrier
 Readily cross the
placenta
 Enter the circulation of
the developing fetus

20. Biotransformation
Detoxificatoin

21.  Toxicity of drug
proportional to
 Rate of absorption –
into CV
 Rate of removal – from
CV
 with tissue uptake and
metabolism

22. Metabolism
Esthers
 Esther
 are hydrolyzed in blood
plasma by enzyme
 Pseudocholinesterase
 Rate of hydrolysis
impacts toxicity
 Some esters converted to
PABA
 Some people have
Atypical form of
Pseudocholinesterase
 Unable to hydrolyze
esthers
 Increased toxicity
 Hereditary trait
 Influences GA
 Succinylcholine isn’t
metabolized

23.  Absolute contraindication
 Under no circumstance
should the drug be
administered
 Possibly toxic or lethal
reaction
 Relative Contraindication
 May be administered to
patient after careful
consideration of the risks and
benefits
 The smallest clinically
effective dose should be
given
 Due to potential for adverse
reaction

25. Amide anesthetics
 Primary site of
biotransformation is the
liver
 Liver function and
perfusion influences rate
of metabolism
 Both amide and esther
 Metabolized in blood
and liver
 Shorter half life due to
plasma cholinesterase
 metabolizes it quickly
Articane - Hybrid LA

27.  Metabolic byproducts of LA can cause clinical activity
 Lidocaine – metabolic byproduct
 monoethylglycinexylidide
 and glycine xylidide
 Causes sedation effect
 Prilocaine can cause methemoglobinemia when
administered in large doses
 Orthotoluidine
 primary metabolite that causes the condition

28.  Kidneys are the primary route of excretion
 For both the LA and its metabolites
 Patients with significant renal disease may be unable
to eliminate the LA or metabolites
 Results in high blood levels
 Possible toxicity
 Patient with dialysis and renal impairment
 need a medical consult

29. LA reversibly block action potentials in
ALL excitable neural membranes
Central nervous system
Cardiovascular system

31.  LA readily cross the blood brain barrier and placenta
 Action is to depress neural transmission
 By suppressing the sodium pump
 At low levels – no CNS effect
 At high levels – generalized tonic-clonic convulsions
 LA have been used as anticonvulsant at blood levels
below seizure thresholds
 Used for tx of epilepsy
 By raising the firing threshold (action potential)
 Diminishing the excitability of neuronal activity

32.  CNS is more susceptible to LA
 Is the initial clinical indication of LA toxicity
 Initially a mild sedation or drowsiness
 Toxic levels increase and CO2 increases
 As CO2 increases
 the level of LA needed for seizures decreases
 Seizures will occur and increase
 Duration of seizures is proportional to blood level of
LA

33.  Seizures cause increase in blood flow to CNS
 This increases the concentration of LA in CNS
 Cerebral metabolism increases with seizures
 Acidosis increases (hypercarbia)
 This lowers the threshold for seizures and level of LA
needed to cause seizures
 Further increases in LA concentration causes
 Cessation of seizures
 Due to generalized CNS depression
 Flat EEG

34.  LA are thought to inhibit the “inhibitory pathways” of
the cerebral cortex
 This allows the facilitory (excitatory) pathways to
dominate
 The balance between inhibition and facilitation is lost
and seizures occur

35.  LA cause generalized
analgesia
 Decrease the pain
threshold
 Suppressing the afferent
registration of pain
 Relatively low safety
margin
 between analgesia and
overdose

36. Mood elevation
euphoria inducing and fatigue lessening
Cocaine
has been abused for decades

38. Direct action on myocardium – depression
 Decrease in excitability of myocardium
 Decrease in conduction rate and force of contraction
 Diminished cardiac output
 Conduction & rhythm may be modified
 Antidysrythmic – used in ACLS
 Related to blood level of LA

39.  Peripheral vasculature
 Cocaine – vasoconstriction
 All other LA produce vasodilation
 Relaxation of smooth muscle in BV walls
 Increased blood flow
 Increased drug absorption and distribution
 Decreased depth & duration of LA
 Increased bleeding
 Increased LA blood levels

40.  Primary effect on Blood Pressure
 Hypotension
 Procaine
 may cause 50% of patients to be hypotensive
 other LA 6%
 At non-overdose levels no change in BP
 Near overdose slight drop in BP due to dilation of BV
 At overdose – profound hypotension
 Caused by decreased
 myocardial contractility & cardiac output
 vasodilation with peripheral resistance
 Lethal levels – CV collapse

41.  Direct relaxation
 on bronchial smooth muscle
 OD levels – respiratory arrest
 Due to CNS depression
 At therapeutic (normal) levels
 No effect on respiration

42.  Due to block of transmission of impulse
 Sodium pump
 diffusion is blocked in the sodium channels
 Can be additive to
 succinylcholine and
 muscle relaxants
 OTHER PRESCRIPTIONS – DEPRESSANTS
 Abnormal period of muscle inactivity or paralysis

43.  LA potentiate
 all CNS depressants and their actions
 Common metabolic pathways
 Drug concentrations are elevated due to prolonged
metabolism
 Toxic levels can be reached with lower doses
 Hepatic microsomal enzymes
 May be induced by drugs and enhance the metabolism of LA
 Shorten the half life and effectiveness - duration