2. Learning objectives
By the end of this lecture ,students will be able to:
Describe the basic structure of local anaesthetic agents.
Illustrate the relationships between the structure, function and toxicity of local
anaesthetic agents.
Identify the pharmacological profiles of commonly used local anaesthetics
Name and dosage of local anasthetics
2
3. Key points
Local anaesthetic agents are amphipathic molecules.
They bind primarily to sodium channels but also to potassium and
calcium channels, and G-protein- coupled receptors.
Structural modifications alter the physicochemical characteristics of a local
anaesthetic.
Speed of onset, potency, and duration depend on the pKa, lipid solubility
and protein binding, respectively.
All local anaesthetic agents carry a risk of toxicity.
3
4. Introduction
Local anaesthetic agents suppress action potentials in excitable tissues by
blocking voltage-gated Naþ channels.
They inhibit action potentials in nociceptive fibres and so block the
transmission of pain impulses.
4
5. Mechanism of action of local
anaesthetics
Local anaesthetic molecules cross the phospholipid neuronal membrane.
The molecules dissociate dependent on the intracellular pH and the Pka of
the local anaesthetic.
The ionized form binds to open voltage gated Na channels in a reversible
and concentration dependent manner.
The binding of local anaesthetics to open Na channels increases with the
frequency of nerve depolarization.
Bound local anaesthetic drug stabilizes the inactivated receptor state,
preventing further neuronal transmission.
5
7. Pharmacological properties of local
anaesthetics
The speed of onset, potency and duration of local anaesthetics is
dependant on the
pKa,
lipid solubility
protein binding.
7
8. Routes of administration
Local anaesthetics are administered via a number of routes. These include
topical
subcutaneous,
Intravenous
perineal
epidural
intrathecal.
8
12. Pharmacokinetics
Absorption
a) The absorption depend upon the
b) Site of injection
c) rate of injection
d) Dosage
e) Vasoactivity
Intrapleural block is associated with the highest absorption
Subcutaneous infiltration with least absorption.
12
13. Metabolism and clearance
Esters are hydrolysed rapidly in plasma by pseudocholinesterase.
Plasma half-life varies from less than 1 min (chloroprocaine) to 8 min
(tetracaine).
Cocaine, unlike other esters, undergoes hepatic hydrolysis followed by
renal excretion.
Amide metabolism is much slower than plasma hydrolysis.
Amide local anaesthetics are more prone to accumulation in the presence
of hepatic dysfunction or reduced hepatic blood flow
13
14. Ester-type drugs
Cocaine:
The first and most potent local anaesthetic agent, rarely used because of the
problems of misuse.
It is unique in it is ability to produce intense vasoconstriction. Half life 30
minutes.
Dosage:
Used as topical 4 – 10% solution
Maximum dose is 1.5 mg/kg – 100mg max.
Used intranasally during apical surgery.
14
15. Ester-type drugs
Procaine:
The only indication for its use in dentistry is in
patients with proven allergy to the amide group.
Used intra-arterially, as part of the recognized
regimen, to treat the arteriospasm which might
occur during intravenous sedation.
It has an excellent vasodilatory properties.
15
16. Ester-type drugs
Procaine (cont)
Onset & duration of Action:
Has a very shot duration (5 minutes) and a long onset
time of 10 minutes
Dosages:
The maximum dose is 6 mg/kg, 400 mg max.
Metabolism:
Rapidly by plasma esterase.
16
17. Ester-type drugs
Benzocaine:
Used mainly as topical, due to its poor water solubility, and because of its low
toxicity, it is used in concentration up to 20%.
Hydrolyzed rapidly by plasma esterase to p-aminobenzoic acid accounting
for its low toxicity.
17
18. Amide-type drugs:
Lignocaine (Lidocaine):
Synthesized in 1943 and used in dentistry since 1948 and is also known as
Xylocaine
It highly lipophilic (partition coefficient 3) , rapidly absorbed.
Metabolized only in the liver and its metabolites are less toxic with no action.
Has half-life of 90 minutes
18
19. Amide-type drugs
Lignocaine (cont)
Dosage:
4.4 mg/kg – 300 mg max
Used as 2% plain or with 1:80 000 epinephrine
4 and 10% spray, 2% gel and 5% ointments.
Onset & duration of action:
Rapid onset 2 – 3 minutes
Plain- short duration (10 minutes)
With epinephrine- intermediate duration (45 – 60 minutes)
19
20. Amide-type drugs
Prilocaine:
A very potent local anaesthetic and is less toxic than Lignocaine.
It produces less vasodilatation than lignocaine
Rate of clearance is higher than other amide-types, suggesting extra-
hepatic metabolism with relatively low blood concentration.
It’s metabolite o-toluidine lead to methaemo-globinaemia (more than
600 mg in adults)
20
21. Amide-type drugs
Prilocaine:
Used either plain 4% or 3% combined with 0.03IU/mL of Felypressin as
vasoconstrictor.
Onset & Duration:
Slower onset – 4 minutes.
It’s duration of action is similar to Lignocaine.
Dosage;
6.0 mg/kg – max. 400 mg.
Combined with Lignocaine as a topical anaesthetic agent to be used prior to
vene-section and during dental sedation in children.
21
22. Amide-type drugs
Mepivacaine:
Possess the least vasodilating effect.
Metabolized in the liver and has t0.5 of 120 minutes.
It’s main indication is when local anaesthetic without
vasoconstrictor is needed. 3% plain is more effective than
lignocaine.
Onset & duration:
Rapid onset but slightly shorter duration.
22
23. Amide-type drugs
Bupivacaine:
A long-acting local anaesthetic agent, with a t0.5 of 160
minutes due grater binding capacity to plasma protein and
tissue proteins
Metabolized in the liver.
Used mainly in Oral surgical procedures for its long-lasting
pain control.
Longer onset and longer duration (Regional 6 – 8 hors)
Dosage:
1.3 mg/kg – Max 90 mg
23
24. Amide-type drugs
Etidocaine:
A long-acting agent similar to Bupivacaine but with faster onset.
Metabolized in the liver.
Dosage:
8 mg/kg – Max 400 mg
1.5% with 1:200 000 epinephrine.
Lignocaine is the most common used agent both topically
and by injection as 2% with or without adrenaline, with a
maximum dose of 4.4 mg/kg.
24
