Anaesthesia & Exodontia Third Year

1. Pharmacology of Local Anesthetics
By
Hesham Marei
BDs, MSc, PhD, MFDS (RCS-Eng)

2.  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.

3. Pharmacokinetics of
LA




Uptake
Distribution
Biotransformation
Excretion

4. Uptake
 When injected into soft tissue, LA exerts a
pharmacological action on blood vessels in the
area. All LA have a degree of vasoactivity,
most producing dilatation of the vascular bed
into which they are deposited.
 Procaine (Ester LA) is the most potent
vasodilator drug
 Cocaine
is
the
only
LA
producing
vasoconstriction.

5. A
significant
clinical
effect
of
vasodilatation is an increase in the rate
of absorption of LA into the blood.
Decreasing in the duration, quality, and
depth of pain control while increasing the
possibility of toxic overdose.

6. 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
vasoactivity of the drug. (IV, IM,SC).

7. Distribution
 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.

8. The blood level of LA
is influenced by:
1. Rate of absorption
2. Rate of distribution of the drug from the
vascular compartment to the tissues
3. Elimination of the drug through
metabolic or excretory pathways.

Elimination half life: is the time
necessary for 50% reduction in the
blood level.

9. Metabolism
(Biotransformation)
 Ester LA
Hydrolyzed in the plasma by the enzyme
pseudocholinesterase.
 Amide LA
The primary site of biotransformation of
amide LA is the liver therefore liver
function and hepatic perfusion influence
the rate of biotransformation.

10. 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.

11. Systemic action of LA




CNS
CVS
Respiratory System
Local tissue toxicity

12. CNS
I-Anticonvulsant Properties:
 Procaine, mepivacaine, and lidocaine have
been used IV to terminate or decrease the
duration of both grand mal, and petite mal
seizures.
 The anticonvulsive blood level of lidocaine is
0.5 to 4µg/ml.
 Epileptic patients possess hyperexcitable
cortical neurons at a site with in the brain. LA
has a depressant action on CNS, raise the
seizure threshold by decreasing the excitability
of these neurons.

13. II- Pre-convulsive SS:
The initial 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
patient.
The initial 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.

14. 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

15. 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.

16. Respiratory System
 At non-overdose level, they have a direct
relaxant action on bronchial smooth
muscle, where as at overdose levels they
may produce respiratory arrest as a
result of generalized CNS depression.

17. Local tissue Toxicity
 Skeletal muscle appears to be more
sensitive to the local irritant properties of
LA than other tissues. Longer acting LA
produce more localized skeletal muscle
damage than shorter acting drugs.

18. Amides
Lidocaine
Mepivacaine
Prilocaine
Bupivacine

19. Esters
Procaine
Cocaine
Benzocaine
Tetracaine

20. Lidocaine
Concentration - 2%
Potency - 2X Procaine
Toxicity - 2X Procaine
Metabolized - Liver
Excreted - Kidney

21. Lidocaine
Time to onset
Half life
Max rec dose
(Malamed)
(manufac.)
w/o epi
with epi
2-3 mins
90 mins
4.4 mg/kg (2 mg/lb)
4.4 mg/kg (2 mg/lb)
6.6 mg/kg (3 mg/lb)

22. Lidocaine
Maximum safe dose - 2% with
1:100,000epi
Malamed - 300 mg or 8 carpules
manufac. - 500 mg or 13.5 carpules

23. Mepivacaine
Concentration - 2% or 3%
Potency - 2X Procaine
Toxicity - 1.5-2X Procaine
Metabolized - Liver
Excreted - Kidney

24. Mepivacaine
%
Vasoconstrictor
3
without
mins
Duration *
pulp - 20-40
tissue - 2-3 hrs
2
1:20,000
mins
Levonordefrin
pulp - 60-90
tissue - 3-5 hrs

25. Mepivacine
Time to onset
Half life
Max rec dose
(Malamed)
(manufac.)
1.5-2 mins
1.9 hrs
4.4 mg/kg (2 mg/lb)
6.6 mg/kg (3 mg/lb)

26. Mepivacaine
Maximum safe dose - 3% w/o
vasoconstrictor
Malamed - 300 mg or 5.5 carpules
manufac. - 400 mg or 8 carpules

27. Mepivacaine
Maximum safe dose - 2% with constrictor
Malamed - 300 mg or 8 carpules
manufac. - 400 mg or 11 carpules

28. Bupivacaine
Concentration - 0.5%
Potency - 8X Procaine (4X Lidocaine)
Toxicity - 8X Procaine (4X Lidocaine)
Metabolized - Liver
Excreted - Kidney

29. Bupivacaine
%
Vasoconstrictor
0.5
1:200,000 epi
mins
Duration
pulp - 90-180
tissue - 4-9 hrs,
up to 12 hrs
reported

30. Bupivacaine
Time to onset
Half life
Max rec dose
Max safe dose
6-10 mins
2.7 hrs
1.3 mg/kg (0.6 mg/lb)
90 mg or 10 carpules

31. Procaine
Concentration - 2-4%
Potency - 1
Toxicity - 1
Metabolized - hydrolyzed in plasma by
pseudocholinesterase to PABA
Excreted - Kidney
No longer available in dental carpules

32. Procaine
Time to onset
Half life
Duration
(with v/c)
Max rec dose
Max safe dose
6-10 mins
0.1 hr
pulp - 30-60 mins
tissue - 2-3 hrs
6.6 mg/kg (3 mg/lb)
400 mg

33. 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

34. Dosage of LA in children
 Young’s rule (age) & Clark’s rule (weight)
Which is accurate?
 Max. child dose = child weight (kg)/70kg X max. adult
dose.
E.g.:
Child dose of lidocaine with adrenalin =
20/70 X 500 mg = 143 mg
Child dose of lidocaine without adrenalin =
20/70 X 300 mg = 86 mg

35. LA agents and
vasoconstrictors

36. Importance of adding VC

What is the value of adding VC to the LA
solution?
1.…….
2.……..
3.……..
4.……….
5……….

37. Vasoconstrictors
Constrict blood vessels
Decrease blood flow
Decrease the blood level of the drug
Increase the concentration of drug at the
site
Decrease bleeding at site

38. Factors in
Selection of
Vasoconstrictor
Length of the dental procedure
The need for hemostasis during and
following procedure
The medical status of the patient

39. Dosage of vasoconstrictor
 1:100,000 means 1 gm (1000 mg)/100,000 mL.
= 0.01 mg/ml
 E.g.: concentration of adrenalin in a solution =
1:50,000
Therefore each mL contains = 1000/50,000
=1/50 = 0.02 mg/mL.
The cartridge contents = 0.02 X 2 or (1.8) = 0.04
mg. = 40 microgram

40. References
 Meechan, et al., Hand book of local
anaesthesia, 1998. SF
 Malamed: Pain and anxiety control for
the conscious dental patient, 1997.