Download Local anesthesia

Local anesthesia
Lecture 3
Composition of local anesthetic solution
• Local anesthetic agent
• Vasoconstrictor
• Preservative
• Reducing agent
• Fungicidal agent
• Sodium chloride and distilled water
Local anesthetic agent






Amide
Lidocaine
Mepivicaine
Prilocaine
Articaine
Bupivicaine
Etidocaine
Ester
 Cocaine
 Procaine
 Propoxycaine
back
Lidocaine
Most common agent Onset of action = 2-3
Discovered in 1948
( min
first of amide group) Duration = 60 min
(pulpal) and 60-120
Regarded as the
min (soft tissue)
standard
Maximum
Minimal allergisity
Have topical anesthetic recommended dose
(MRD)= 4.4mg/kg
activity
=300 mg
Vasodilating activity
PKa =7.9
Metabolism and safety
Lidocaine metabolized in liver and excreted
in urine (10% unchanged completely)
On CNS large dose cause initial stimulation
followed by depression ( anticonvulsant
effect)
On CVS large dose cause myocardial
depression ( used in ventricular tachycardia)
Maximum dose calculation
Available concentration =2% =2gm in
each 100 ml /100
→→→→ 0.02gm/ml = 20 mg/ml
*1.8ml/dental cartridge =36 mg /dental
cartridge
300 /36 = 8.3 dental cartridge (MRD)
back
Mepivicaine
Less toxic than
Same potency to
lidocaine
lidocaine
Used for child and
Similar to lidocaine
geriatric patient when
in metabolism and
vasoconstrictor
excretion
contraindicated
Same onset
MRD =4.4 mg/Kg=
 slight extended
300mg
duration (weak
2% → 8.3 cartridge
vasodilatation)
3% → 5.5
PKa =7.6
cartridge
back
Prilocaine (citanest)







Same potency to lidocaine
Less toxicity
Less vasoldilating activity
PKa =7.9
MRD =6mg/kg
3% → 7.5 cartridge
4% → 5 cartridge
Prilocaine (citanest)
Metabolism occur mostly in liver into
orthotolidine which can cause
methemoglobulinemia in susceptible
individual (patient with hemolytic anemia) if
used in large dose → poor oxygen carrying
capacity resulting in cyanosis
Clinically patient may have cyanosis in the
lip, mucous membrane and skin. Patient may
also have respiratory distress in severe cases
Treatment by methyline blue 1% injection 1-2
back
mg/kg IV/5min
Articaine
Slightly more potent than lidocaine
Similar toxicity, and vasodilating activity
Some literature present a cross allergisity
with sulfate so it is best to be avoided in
patient allergic to sulfonamide
MRD =7mg/kg
4% → 7 cartridge
Similar to prilocaine in producing
methemoglbulinemia
back
Bupivicaine
Four times more
Dental Indication
potent than lidocaine 1. Prolonged dental
and 4 times less toxic
procedure
Slower onset (5-10
2. Expected post
min) and extended
operative pain
duration lasting for
90-180 min
Contraindication
MRD =1.3mg/kg
Child
and
mentally
0.5% → 10 cartridge
retarded patient
back
Etidocaine
Similar to bupivicaine except:
 More toxic than lidocaine
 MRD= 8mg /kg available in1.5% → 13
cartridge
In general surgery both indicated in
prolonged procedure when uses of
vasoconstrictor is contraindicated
systemically or locally
back
Local anesthetic agent






Amide
Lidocaine
Mepivicaine
Prilocaine
Articaine
Bupivicaine
Etidocaine
Ester
 Cocaine
 Procaine
 Propoxycaine
back
Cocaine
Oldest anesthetic agent used since 18th
century
It is the only agent having a
vasoconstrictor activity( sympathomimatic
activity) and can be used topically because
it is rapidly absorbed through mucous
membrane
It has liability for dependence which makes
its uses very limited
back
Procaine
Has 50% potency
and toxicity than
lidocaine
It has prominent
vasodilating activity
which reduce its
duration
PKa =9.1 (slow
onset)
MRD =1000mg
Its hydrolyses
occurs in plasma by
enzyme
pseudocholine
esterase
High incidence of
allergisity
back
Propoxycaine
More potent and more toxic than lidocaine
Has rapid onset and adequate duration
It is available in combination form with
procaine to reduce toxicity
0.4% propoxycaine + 2% procaine
=24mg/ml
MRD =400 mg
It is indicated only in patient allergic to
amide form of local anesthesia
back
Composition of local anesthetic solution
• Local anesthetic agent
• Vasoconstrictor
• Preservative
• Reducing agent
• Fungicidal agent
• Sodium chloride and distilled water
Vasoconstrictor
Advantages of vasoconstrictor in combination
with local anesthesia:
1. Reduce blood flow thus reduce bleeding
2. Reduce local anesthetic absorption and
toxicity (reduce systemic effect)
3. Increase duration and depth of
anesthesia
Types of vasoconstrictor
1. Adrenergic agonist agent
2. Vasopressin
Adrenergic agonist agent
(sympathomimetic agent) - catecholamine
Mode of action:
1. Direct (binding)
2. Indirect (displacing)
3. Mixed action
Sympathetic receptors:
1. 1 vasoconstriction
2. 2 Reuptake
3. 1 Cardiac stimulation
4. 2 Vasodilatation
Affinity of adrenergic agents on receptors
1 2 1
2
Adrenaline
++
++
++
++
Nor - adrenaline
++
++
-
-
Levonordephrine
+
++
++
+
Phenylphrine
+
+
-
-
HO
HO
CH
CH
NH
OH
1
2
1
2
Epinephrine
H
Levonordefrin
CH 3
CH 3
H
H
Norepinephrine
H
Adrenergic Receptor Binding
+
NH 3
VII
VI
HO
V
HO
O
H
I
N+
IV
II
III
COO –
Adrenaline
Synthetic or natural abstract from
adrenal medulla . It is the most common
and potent vasoconstrictor.
Concentration:
Expressed in ratio gm: ml / 1: 100000
Meaning 1 gm in 100000 ml
Concentration
1:100000 means:
=1 gm in 100000 ml
=1000 mg in 100000 ml
= 0.01 mg /ml
In single dental cartridge (1.8 ml)
= 0.018 mg =18 g (microgram)
Adrenaline availability (concentration)
1:1000 (alone) is used for control of
bleeding?
contraindicated in arterial bleeding- Rebound
bleeding
1:50000 for surgery where hemostasis is
necessary
1:80000 and 1:100000 commonly used
concentration
1:200000 low concentration used for
medically compromised patient
(vasoconstrictor contraindicated) and where
hemostasis is of little importance
Maximum recommended dose (MRD)
MRD
(mg)
Available
Potency
concentration
Adrenaline
0.2
100
Nor - adrenaline
0.34
1:30000
25
Phenylphrine
4
1:2500
5
levonordephrine
1
1:20000
15
Other adrenergic agonist vasoconstrictor
 Nor-adrenaline and phenylphrine have
prominent alpha activity comparing to beta
activity which may result in severe
vasoconstriction (increase blood pressure)
and ischemia.
 It is contraindicated in patients with cardiac
problem.
 It is contraindicated in terminal extremities
Metabolism of catecholamines
Adrenergic
nerve terminal
Extraneuronal
tissues
Renal
excretion
[ COMT]
MAO
[ COMT ]
Injected
drug
 Receptor
COMT: Catechol-O-methyltransferase
MAO: monoamine oxidase
Side effects and overdose
• CNS:
Fear apprehension palpitation
• CVS: Cardiac stimulant effects , increase
blood pressure and rebound bleeding at
prolonged dental procedure.
Causes of rebound bleeding:
Adrenaline selectivity on receptor:
 Low concentration  effect
 High concentration  effect
Limitation of adrenergic vasoconstrictor
• Precautions/contraindications
– Uncontrolled Cardiovascular disease
– Uncontrolled thyrotoxic goiter
• Drug interactions
– Tricyclic antidepressants
– General anesthetics
– Adrenergic antagonists
– COMT inhibitors
– Not MAO inhibitors
Vasoconstrictors (epinephrine,
Levonordefrin)
with
Tricyclic antidepressants (imipramine,
desipramine)
Hypertensive and/or cardiac reactions –
are more likely. Use epinephrine
cautiously; avoid Levonordefrin.
Vasoconstrictors (epinephrine,
Levonordefrin)
with
Volatile anesthetics
(halothane)
Increased possibility of cardiac –
arrhythmias exists for some agents.
Vasoconstrictors (epinephrine,
Levonordefrin)
with
Nonselective beta blockers
(Propranolol, Nadolol)
Hypertensive and/or cardiac reactions –
are more likely. Use cautiously.
Vasoconstrictors (Epinephrine,
Levonordefrin)
with
COMT inhibitors
(Tolcapone, Entacapone)
Hypertensive and/or cardiac reactions –
are more likely. Use cautiously.
Consideration
MRD for cardiovascular disease patient =
0.04 mg of adrenaline = 2 dental cartridge
of 2ml 1:100000 concentration adrenaline
Controversy still exists on using adrenaline
in controlled cardiovascular diseased
patient. Explain why?
Uses of small amount available in dental
cartridge is better than exposing the
patient to failure anesthesia which
produce pain and bleeding that can
stimulate fear and increase intrinsic
adrenaline that may have more
dangerous effect than extrinsic
adrenaline
Vasopressin (Felypressin)
Synthetic analogue of posterior pituitary
hormone (Octopressin)
Act on V1 receptor that is found on
venous site of microcirculation
It posses mild hemostatic effect and used
only when other vasoconstrictor
contraindicated
Available concentration = 0.03 IU/ml in
combination with prilocaine 2% or 3%
MRD= 0.27 IU
back
Preservative
Maintains sterility of the solution
Caprylhydrocuprienotoxin used
for this purpose
Methylparaben used in the past
but nowadays not used ?
back
Reducing agent
(in vasoconstrictor containing solution)
 Antioxidant (reducing agent) used to
prevent oxidation of vasoconstrictor that
may deteriorate on exposure to sunlight
(brown discoloration)
 Sodium metabisulfite used for this purpose
 On exposure to oxygen it will diffuse
through the rubber of the cartridge where
sodium metabisulfite will be converted to
sodium metabisulfate (oxidized)
 Oxidized instead of vasoconstrictor
 Why is an old solution more acidic? Painful
back
? Irritant?
Fungicide
Thymol
Sodium chloride and distilled water
(ringers solution)
For isotonicity of injected solution to
reduce edema and discomfort on
injection